Prophylaxis of VTE in Medical Patients and

Long Distance Travelers i

Guideline Panel Members

Saudi Expert Panel
 Dr. Fahad Al-Hameed*
 Dr. Mohamed A. Abdelaal*
 Dr. Ali Alaklabi*
 Dr. Salah Aldahan
 Dr. Hasan Al-Dorzi*
 Dr. Yousef Alomi
 Dr. Mohammad Al Baik
 Dr. Ebtisam Bakhsh*

*Saudi Association for Venous Thrombo-Embolism (SAVTE) (www.savte.com)

McMaster University Working Group

Elie A Akl, MD PhD, Reem Waziry, MD MPH, Andrea J Darzi, MD MPH, Jan Brozek, MD PhD,
and Holger Schünemann, MD PhD on behalf of the McMaster Guideline Working Group

Acknowledgements
We acknowledge Prof. Mohammed Addar, Dr. Abdulelah Qadi, Dr.Tarig Al Khuwaitir, Prof.
Fawzi Al Jassir, Prof. Mohamed Alhajjaj, and Prof. Essam Aboelnazar for their contribution to
this work.

We gratefully acknowledge Dr Ayman Afify from Prince Sultan Military Medical City for peer
reviewing this final report.

Disclosure of potential conflict of interest:

Dr. Hasan Al-Dorzi declared receiving a grant from MSD for research on invasive candidiasis
and received honoraria April 2014 from Sanofi Aventis for being a speaker at an educational
program on DVT in ICU.

Dr. Ebtisam Bakhsh declared receiving monetary and non-monetary support from organiza-
tions and also received speaker’s honoraria for lecturing on relevant topics in international
conferences and meetings.

Dr. Mohamed Alhajjaj declared participating in multi-center research and receiving medical
equipment (spirometry devices) to complete a survey project. He also received speaker’s
honoraria for lecturing on pulmonary topics in meetings sponsored by drug companies.
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers ii

Dr. Ali Alaklabi declared travelling to meetings and monetary costs being covered by Sanofi
and Bayer.

Dr. Fahad Al-Hameed declared receiving research grants and sponsorships from Sanofi and
Bayer, the interest belongs to the association SAVTE and himself.

Funding:
This clinical practice guideline was funded by the Ministry of Health, Saudi Arabia.

Address for correspondence:

Saudi Center for Evidence Based Health Care
E-mail: ebhc@moh.gov.sa
Web: http://www.moh.gov.sa/endepts/Proofs/Pages/home.aspx

Abbreviations:

DVT: deep vein thrombosis

EtD: Evidence-to-Decision
GRADE: Grading of Recommendations, Assessment, Development and Evaluation
KSA: Kingdom of Saudi Arabia
LMWH: low molecular weight heparin
PE: pulmonary embolism
VTE: venous thromboembolism
UFH: unfractionated Heparin
GCS: graduated compression stockings
IPC: intermittent pneumatic compression
SCD: sequential compression device
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers iii

Contents
The Saudi Center for Evidence Based Health Care (EBHC) ..................................................................... v
Executive Summary................................................................................................................................. 1
Introduction ........................................................................................................................................ 1
Methodology....................................................................................................................................... 1
How to use these guidelines ............................................................................................................... 2
Key questions ...................................................................................................................................... 2
Recommendations .............................................................................................................................. 3
Scope and purpose.................................................................................................................................. 6
Introduction ............................................................................................................................................ 6
Methodology........................................................................................................................................... 6
How to use these guidelines ................................................................................................................... 7
Key questions .......................................................................................................................................... 8
Recommendations .................................................................................................................................. 8
Question 1: Should heparin versus no heparin be used for prophylaxis of VTE in acutely ill medical
patients? ............................................................................................................................................. 8
Question 2: Should low molecular weight heparin versus unfractionated heparin be used for
prophylaxis of VTE in acutely ill medical patients? ........................................................................... 10
Question 3: Should extended duration (i.e., up to 30 or 40 days) versus a regular duration (i.e., up
to 10 days) be used for the thromboprophylaxis of VTE in acutely ill hospitalized medical patients?
.......................................................................................................................................................... 11
Question 4: Should GCS versus no GCS be used for hospitalized medical patients? ....................... 12
Question 5: Should IPC versus no IPC be used for hospitalized medical patients? .......................... 14
Question 6: Should heparin versus placebo be used for critically ill patients? ................................ 15
Question 7: Should LMWH versus UFH be used for critically ill patients? ....................................... 16
Question 8: Should GCS versus no GCS be used for critically ill patients? ....................................... 17
Question 9: Should IPC versus no IPC be used for critically ill patients? .......................................... 18
Question 10: Should thromboprophylaxis be used for Prophylaxis of DVT in chronically ill medical
patients? ........................................................................................................................................... 19
Question 11: Should frequent ambulation be used for long-distance travelers at increased risk of
VTE? .................................................................................................................................................. 19
Question 12: Should calf muscle exercise versus no calf muscle exercise be used for VTE in long
distance travelers? ............................................................................................................................ 20
Question 13: Should sitting in an aisle seat versus no sitting in an aisle seat be used for VTE in long
distance travelers? ............................................................................................................................ 20
Question 14: Should anticoagulants versus no anticoagulants be used for VTE in long distance
travelers? .......................................................................................................................................... 21
Question 15: Should GCS versus no GCS be used for VTE in long distance travelers? ..................... 21
References ............................................................................................................................................ 23
Appendices............................................................................................................................................ 26
Appendix 1: Evidence to Decision Frameworks ................................................................................ 27
Guideline Question 1: Should heparin versus no heparin be used for prophylaxis of DVT in
acutely ill medical patients? .......................................................................................................... 27
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers iv

Guideline Question 2: Should low molecular weight heparin versus unfractionated heparin be
used for prophylaxis of VTE in acutely ill medical patients? ......................................................... 35
Guideline Question 3: Should extended duration (i.e., up to 30 or 40 days) versus a regular
duration (i.e., up to 10 days) be used for the thromboprophylaxis of VTE in acutely ill
hospitalized medical patients?...................................................................................................... 43
Guideline Question 4: Should GCS versus no GCS be used for hospitalized medical patients? ... 50
Guideline Question 5: Should IPC versus no IPC be used for hospitalized medical patients? ...... 57
Guideline Question 6: Should Heparin versus Placebo be used for critically ill patients? ............ 64
Guideline Question 7: Should LMWH versus UFH be used for critically ill patients? ................... 71
Guideline Question 8: Should GCS versus no GCS be used for critically ill patients? ................... 79
Guideline Question 9: Should IPC versus no IPC be used for critically ill patients? ...................... 88
Guideline Question 10: Should thromboprophylaxis be used for prophylaxis of DVT in
chronically ill medical patients? .................................................................................................... 96
Guideline Question 11: Should frequent ambulation be used for long-distance travelers at
increased risk of VTE? ................................................................................................................. 101
Guideline Question 12: Should calf muscle exercise versus no calf muscle exercise be used for
VTE in long distance travelers? ................................................................................................... 107
Guideline Question 13: Should sitting in an aisle seat versus no sitting in an aisle seat be used
for VTE in long distance travelers?.............................................................................................. 113
Guideline Question 14: Should anticoagulants versus no anticoagulants be used for VTE in long
distance travelers? ...................................................................................................................... 119
Guideline Question 15: Should GCS versus no GCS be used for VTE in long distance travelers?
..................................................................................................................................................... 125
Appendix 2: Search Strategies and Results ..................................................................................... 132
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
v

The Saudi Center for Evidence Based Health Care (EBHC)

The Saudi Centre for Evidence Based Health Care has managed and supported the coordination of
the process of clinical practice guideline (CPG) development between the methodological team from
McMaster University and the local clinical expert panel members in Saudi Arabia.

The EBHC staff members recruited local clinical experts through contacting Saudi specialist societies
including the Saudi Association for Venous thromboembolism (SAVTE) and also independent experts
interested in developing reliable and most up-to-date CPGs to harmonize the treatment and provide
the highest quality of health care in the kingdom of Saudi Arabia. These experts were health care
professionals of multidisciplinary backgrounds. As much as possible, patient’s representatives were
also included in panels.

In an effort to make national recommendations, the participating experts were professionals from
the Ministry of Health (MoH), National Guard Hospitals, King Faisal Specialist Hospital and Research
Centre (KFSHRC), University Hospitals, Security Forces Hospitals, Prince Sultan Military Medical City
(PSMMC) and from some private hospitals.

Based on a preselection of available evidence syntheses, the EBHC provided a list of potential topics
to be addressed in CPGs after thorough consultations with the local stakeholders. These topics were
further discussed with the McMaster team for important selection criteria and agreed on 12 topics
for wave 2.

The guideline panel meetings were held in Riyadh on 15th-18th March 2015 where about 96 local ex-
perts working in Saudi Arabia participated with the methodological support from 20 experts from
McMaster University and its partners from the American University of Beirut, Lebanon, and the Uni-
versity of Freiburg, Germany, in providing high quality recommendations for common and important
clinical conditions in the Kingdom.

The Saudi Centre for EBHC supports the efforts for dissemination of the CPGs by publishing online
the full reports of the CPGs, facilitates writing concise versions of the CPGs for publication in peer
reviewed medical journals, sending hard copies to hospitals and health care centers. Finally, a mo-
bile App has been introduced in KSA to facilitate the dissemination efforts of the completed practice
guidelines.

The staff members at the Saudi Centre for EBHC:

Dr Zulfa Al Rayess, Consultant Family Medicine, Head of Saudi Center for EBHC
Dr Yaser Adi, Scientific Advisor for the Saudi Centre for EBHC
Miss Nourah Al Moufarreh, Project Manager, Saudi Center for EBHC
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
Executive Summary
Introduction
Deep venous thromboembolism is one of the
most common conditions among medically ill
patients.1,2 Although it is a preventable condi-
tion, it remains a leading cause of mortality,
morbidity and increasing health expenditures
in this cohort.1,3,4 Critically ill patients and
chronically ill patients are especially at risk of
developing venous thromboembolism.2,5 Risk
factors include severe illness, sedating medi-
cations and invasive procedures.2,6 Heparin
administration for patients at risk has been
shown to reduce the occurrence of deep ve-
nous thrombosis, however it might also in-
crease the risk of bleeding.1 Thus graduated
compression stockings (GCS) and intermittent
pneumatic compression (IPC) were suggested
as alternatives for patients who might not tol-
erate the adverse events of anticoagulants.7
The available evidence about venous throm-
boembolism in the Kingdom of Saudi Arabia
includes a recent study that looked at the
morbidity and mortality related to venous
thromboembolism in King Fahd general hospi-
tal in Jeddah. The study estimated a period
prevalence of 500 cases clinically diagnosed
with VTE between July 2008 and June 2009, of
whom only 36.5% received prophylactic an-
tithrombotic therapy. Case fatality rates were
estimated to be 31% and 3.1% for those who
did not receive and those who received
prophylactic measures respectively.8 The aim
of this document is therefore to provide the
most recent evidence for prophylaxis of ve-
nous thromboembolism for adult medical pa-
tients in the Kingdom of Saudi Arabia.
Given the importance of this topic, the Minis-
try of Health of the Kingdom of Saudi Arabia
with the support of the McMaster University
working group produced practice guidelines
to assist health care providers in evidence-
based decision-making on the prophylaxis of
venous thromboembolism in medical patients
and long distance travelers.
1
Methodology
This practice guideline is a part of the larger
initiative of the Ministry of Health of the King-
dom of Saudi Arabia (KSA) supported by
McMaster University to establish a program
of rigorous development of guidelines. The
ultimate goals are to provide guidance for cli-
nicians and other healthcare decision makers
and reduce unnecessary variability in clinical
practice across the Kingdom.
The Saudi expert guideline panel selected the
topic of this guideline and all healthcare ques-
tions addressed herein using a formal prioriti-
zation process. For all selected questions we
updated existing systematic reviews on the
prophylaxis of venous thromboembolism in
medical patients and long distance travel-
ers.1,2,9 We also conducted systematic search-
es for information that was required to devel-
op full guidelines for the KSA, including
searches for information about patients’ val-
ues and preferences, and costs and resource
use specific to the Saudi context. Based on
these systematic reviews we prepared sum-
maries of available evidence supporting each
recommendation following the GRADE (Grad-
ing of Recommendations, Assessment, Devel-
opment and Evaluation) approach.10 We used
this information to prepare GRADE evidence-
to-decision frameworks that served the guide-
line panel to follow the structured consensus
process and transparently document all deci-
sions made during the meeting (see Appendix
1). The guideline panel met in Riyadh on
March 15 & 16, 2015 and formulated all rec-
ommendations during this meeting. Potential
conflicts of interests of all panel members
were managed according to the World Health
Organization (WHO) rules.11
As a quality measure for any practice guide-
line prior to publication, the final report have
been externally peer reviewed by a methodo-
logical expert who has not been involved in
this guideline development.
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
2

How to use these guidelines
The guideline working group developed and
graded the recommendations and assessed
the quality of the supporting evidence accord-
ing to the GRADE approach.12 Quality of evi-
dence (confidence in the effect estimates) is
categorized as: high, moderate, low, or very
low based on consideration of risk of bias:
indirectness, inconsistency, imprecision and
publication bias of the estimates as well as
factors that lead to upgrading the quality of
the evidence. High quality evidence indicates
that we are very confident that the true effect
lies close to that of the estimate of the effect.
Moderate quality evidence indicates moder-
ate confidence, and that the true effect is like-
ly close to the estimate of the effect, but
there is a possibility that it is substantially dif-
ferent. Low quality evidence indicates that
our confidence in the effect estimate is lim-
ited, and that the true effect may be substan-
tially different. Finally, very low quality evi-
dence indicates that the estimate of effect of
interventions is very uncertain, the true effect
is likely to be substantially different from the
effect estimate and further research is likely
to have important potential for reducing the
uncertainty.
The strength of recommendations is ex-
pressed as either strong (‘guideline panel rec-
ommends…’) or conditional (‘guideline panel
suggests…’) and has explicit implications (see
Table 1).13 Understanding the interpretation
of these two grades is essential for sagacious
clinical decision-making.

Table 1: Interpretation of strong and conditional (weak) recommendations

Implications Strong recommendation Conditional (weak) recommendation

For patients Most individuals in this situation
would want the recommended
course of action and only a small
proportion would not. Formal deci-
sion aids are not likely to be needed
to help individuals make decisions
consistent with their values and pref-
erences.
For clinicians Most individuals should receive the
intervention. Adherence to this rec-
ommendation according to the
guideline could be used as a quality
criterion or performance indicator.
For policy makers The recommendation can be adapted
as policy in most situations
The majority of individuals in this situa-
tion would want the suggested course
of action, but many would not.
Recognize that different choices will be
appropriate for individual patients and
that you must help each patient arrive
at a management decision consistent
with his or her values and preferences.
Decision aids may be useful helping
individuals making decisions consistent
with their values and preferences.
Policymaking will require substantial
debate and involvement of various
stakeholders.

Key questions 1. Should heparin versus no heparin be

used for prophylaxis of VTE in acutely
Thromboprophylaxis in acutely ill medical ill medical patients?
patients

2. Should low molecular weight heparin

versus unfractionated heparin be
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
used for prophylaxis of VTE in acutely
ill medical patients?
3. Should extended duration (i.e., up to
30 or 40 days) versus a regular dura-
tion (i.e., up to 10 days) be used for
the thromboprophylaxis of VTE in
acutely ill hospitalized medical pa-
tients?
4. Should graduated compression stock-
ings (GCS) versus no GCS be used for
prophylaxis of DVT in acutely ill medi-
cal patients?
5. Should intermittent pneumatic com-
pression (IPC) versus no IPC be used
for prophylaxis of DVT in acutely ill
medical patients?
Thromboprophylaxis in critically ill medical
patients
6. Should Heparin versus no heparin be
used for critically ill patients?
7. Should LMWH versus UFH be used for
critically ill patients?
8. Should graduated compression stock-
ings (GCS) versus no GCS be used for
critically ill patients?
9. Should Intermittent Pneumatic Com-
pression (IPC) versus no IPC be used
for critically ill patients?
Thromboprophylaxis in chronically ill patients
10. Should thromboprophylaxis be used
for Prophylaxis of DVT in chronically ill
medical patients?
Thromboprophylaxis in long distance travel-
ers
11. Should frequent ambulation be used
for long-distance travelers at in-
creased risk of VTE?
12. Should calf muscle exercise versus no
calf muscle exercise be used for VTE
in long distance travelers?
13. Should sitting in an aisle seat versus
no sitting in an aisle seat be used for
VTE in long distance travelers?
3
14. Should anticoagulants versus no anti-
coagulants be used for VTE in long
distance travelers?
15. Should GCS versus no GCS be used for
VTE in long distance travelers?
Recommendations
Thromboprophylaxis in acutely ill medical
patients
Recommendation 1a:
In acutely ill hospitalized medical patients at
high risk of VTE the panel recommends hepa-
rin (UFH/LMWH) versus no heparin for the
prophylaxis of VTE. (strong recommendation,
moderate quality evidence)
Recommendation 1b:
In acutely ill hospitalized medical patients at
low risk of VTE the panel suggests not using
heparin for the prophylaxis of VTE. (condi-
tional recommendation, low quality evidence)
Remarks:
 Risk stratification should be based on
a validated risk stratification tool (e.g.,
Padua Prediction Score)14
 Decision to provide thromboprophy-
laxis should account for the patients’
risk of bleeding
Recommendation 2:
In acutely ill hospitalized medical patients
the panel suggests using LMWH versus UFH
for the prophylaxis of VTE. (conditional rec-
ommendation, low quality evidence)
Remark: In case of renal failure, use of UFH is
preferred
Recommendation 3:
In acutely ill hospitalized medical patients
the panel recommends a regular duration
(i.e., up to 10 days) versus an extended dura-
tion (i.e., up to 30 or 40 days) for the throm-
boprophylaxis of VTE. (strong recommenda-
tion, moderate quality evidence)
Recommendation 4a:
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
In acutely ill hospitalized medical patients at
low risk of VTE the panel recommends
against using GCS for prophylaxis of VTE.
(strong recommendation, low quality evi-
dence)
Recommendation 4b:
In acutely ill hospitalized medical patients at
high risk of VTE and bleeding (who should
not receive pharmacological prophylaxis) the
panel suggests using GCS for the prophylaxis
of VTE. (conditional recommendation, low
quality evidence)
Remarks:
1. Consider monitoring for skin lesions
and ischemia
2. Physician must ensure proper fitting
Recommendation 5a:
In acutely ill hospitalized medical patients at
low risk of VTE the panel recommends
against using IPC/SCD for prophylaxis of VTE.
(conditional recommendation, low quality
evidence)
Recommendation 5b:
In acutely ill hospitalized medical patients at
high risk of VTE and bleeding (who should
not receive pharmacological prophylaxis) the
panel suggests using IPC/ SCD for the prophy-
laxis of VTE. (conditional recommendation,
low quality evidence)
Remarks: The choice between mechanical
prophylaxis options (GCS versus IPC/SCD) will
depend on the local availability and patience
preference
Thromboprophylaxis in critically ill medical
patients
Recommendation 6:
4
In critically ill medical patients the panel rec-
ommends heparin versus no heparin for the
prophylaxis of VTE. (strong recommendation,
low quality evidence)
Remark: Decision to provide thromboprophy-
laxis should consider the patients’ risk of
bleeding
Recommendation 7:
In critically ill medical patients the panel sug-
gests LMWH versus UFH for the prophylaxis
of VTE. (conditional recommendation, low
quality evidence)
Remark: In case of renal failure, use of UFH is
preferred
Recommendation 8a:
In critically ill medical patients the panel sug-
gests not using GCS for prophylaxis of VTE.
(conditional recommendation, very low quali-
ty evidence)
Recommendation 8b:
In critically ill medical patients at high risk of
bleeding and in whom pharmacological
prophylaxis is not feasible and in settings
where IPC is not available the panel suggests
using GCS for prophylaxis of VTE. (conditional
recommendation, very low quality evidence)
Remarks:
1. Consider monitoring for skin lesions
and ischemia
2. Physician must ensure proper fitting
3. Ensure appropriate use of GCS
(thigh length versus knee length)
Recommendation 9a:
In critically ill medical patients who are
bleeding or at high risk of bleeding, the panel
suggests using IPC/ SCD for the prophylaxis
of VTE. (conditional recommendation, very
low quality evidence)
Recommendation 9b:
In critically ill medical patients at high risk of
VTE receiving pharmacological prophylaxis
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
5

the panel suggests adding IPC/ SCD for the

prophylaxis of VTE. (conditional recommen-
dation, very low quality evidence)
Thromboprophylaxis in chronically ill patients
Recommendation 10:
In chronically ill medical patients the panel
suggests not using versus using prophylaxis
for VTE (conditional recommendation, very
low quality evidence)
Thromboprophylaxis in long distance travel-
ers
Recommendation 11:
In long distance high-risk travelers (>8hrs)
the panel suggests frequent ambulation for
the prophylaxis of VTE. (conditional recom-
mendation, very low quality evidence)
Recommendation 13:
In long distance high-risk travelers (>8hrs)
the panel suggests sitting in an aisle seat for
the prophylaxis of VTE. (conditional recom-
mendation, very low quality evidence)
Recommendation 14:
In long distance travelers (>8hrs) at increased
risk of VTE, the panel suggests using antico-
agulants. (conditional recommendation, very
low quality evidence)
Recommendation 15:
In long distance high-risk travelers (>8hrs)
the panel suggests not using GCS for the pre-
vention of VTE. (conditional recommenda-
tion, very low quality evidence)

Recommendation 12:
In long distance high-risk travelers (>8hrs)
the panel suggests calf muscle exercise for
the prophylaxis of VTE. (conditional recom-
mendation, very low quality evidence)
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
Scope and purpose
The purpose of this document is to provide
guidance about the prophylaxis of venous
thromboembolism in adult medical patients
and long distance travelers. The target audi-
ence of these guidelines includes primary care
physicians and specialists in internal medicine
and cardiology in the Kingdom of Saudi Ara-
bia. Other health care professionals and policy
makers may also benefit from these guide-
lines.
Given the importance of this topic, the Minis-
try of Health (MoH) of Saudi Arabia with the
support of the McMaster University working
group produced practice guidelines to assist
health care providers in evidence-based deci-
sion-making. This practice guideline is a part
of the larger initiative of the Ministry of
Health of Saudi Arabia to establish a program
of rigorous adaptation and de novo develop-
ment of guidelines in the Kingdom; the ulti-
mate goal being to provide guidance for clini-
cians and other healthcare decision makers
and reduce unnecessary variability in clinical
practice across the Kingdom.
Introduction
Deep venous thromboembolism is one of the
most common conditions among medically ill
patients.1,2 Even though it’s a preventable
condition, it remains as a leading cause of
mortality and morbidity and increasing health
expenditures in this cohort.1,3,4 Critically ill
patients and chronically ill patients are espe-
cially at risk of developing venous thrombo-
embolism.2,5
In this document, acutely ill medical patients
refer to patients suffering from acute illness,
and are ill enough to be admitted to the inpa-
tient wards, but not enough to be admitted to
critical care units. Critically ill medical patients
refer to patients suffering from acute illness,
and are ill enough to be admitted to critical
care units. Chronically ill medical patients re-
6
fer to patients suffering from chronic but not
acute illness and are typically bedridden.
The available evidence about venous throm-
boembolism in the Kingdom of Saudi Arabia
includes a recent study that looked at the
morbidity and mortality related to venous
thromboembolism in King Fahd general hospi-
tal in Jeddah. The study estimated a period
prevalence of 500 cases clinically diagnosed
with VTE between July 2008 and June 2009, of
whom only 36.5% received prophylactic an-
tithrombotic therapy. Case fatality rates were
estimated to be 31% and 3.1% for those who
did not receive and those who received
prophylactic measures respectively.8 The aim
of this document is therefore to provide guid-
ance based on the most recent evidence for
prophylaxis of venous thromboembolism for
adult medical patients in the Kingdom of Sau-
di Arabia.
Methodology
To facilitate the interpretation of these guide-
lines we briefly describe the methodology we
used to develop and grade recommendations
and quality of the supporting evidence.
The Saudi expert guideline panel selected the
topic of this guideline and all healthcare ques-
tions addressed herein using a formal prioriti-
zation process. For the selected questions we
updated existing systematic reviews on pre-
vention of venous thromboembolism in acute-
ly ill hospitalized medical patients 1,2 and ex-
tended thromboprophylaxis for medically ill
hospitalized patients. 9
For each question, the McMaster guideline-
working group updated the search strategy to
identify new studies and/or new systematic
reviews. When relevant, the meta-analyses
were updated. We also conducted systematic
searches for information that was required to
develop full guidelines for the KSA, including
searches for information about patients’ val-
ues and preferences, and costs and resource
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
use specific to the Saudi context (see Appen-
dix 2).
Next, we developed for each question an evi-
dence profile and an evidence-to-decision
(EtD) table following the GRADE (Grading of
Recommendations, Assessment, Development
and Evaluation) approach and shared them
with the panel members (see Appendix 1).10,15
The guideline panel was invited to provide
additional information, particularly when pub-
lished evidence was lacking. The final step
consisted of an in-person meeting of the
guideline panel in Riyadh on March 15 & 16,
2015 to formulate the final recommendations.
We used the GRADE evidence-to-decision
frameworks to follow a structured consensus
process and transparently document all deci-
sions made during the meeting. Potential con-
flicts of interests of all panel members were
managed according to the World Health Or-
ganization (WHO) rules.11
Grading of the quality of evidence
The GRADE working group defines the quality
of evidence as the extent of our confidence
that the estimate of an effect is adequate to
support a particular decision or recommenda-
tion.12 We assessed the quality of evidence
using the GRADE approach.
Quality of evidence is classified as “high”,
“moderate”, “low”, or “very low” based on
decisions about methodological characteris-
tics of the available evidence for a specific
health care problem. The definition of each
category is as follows:
 High: We are very confident that the
true effect lies close to that of the es-
timate of the effect.
 Moderate: We are moderately confi-
dent in the effect estimate: The true
effect is likely to be close to the esti-
mate of the effect, but there is a pos-
sibility that it is substantially different.
 Low: Our confidence in the effect es-
timate is limited: The true effect may
be substantially different from the es-
timate of the effect.
7
 Very low: We have very little confi-
dence in the effect estimate: The true
effect is likely to be substantially dif-
ferent from the estimate of effect.
Grading of the strength of recommendations
The GRADE working group defines the
strength of recommendation as the extent to
which we can be confident that desirable ef-
fects of an intervention outweigh undesirable
effects. According to the GRADE approach,
the strength of a recommendation is either
strong or conditional (also known as or called
weak) and has explicit implications.13 Under-
standing the interpretation of these two
grades – either strong or conditional – of the
strength of recommendations is essential for
sagacious clinical decision-making (see Table
1)
As a quality measure for any practice guide-
line prior to publication, the final report have
been externally peer reviewed by a methodo-
logical expert who has not been involved in
this guideline development.
How to use these guide-
lines
The Ministry of Health of Saudi Arabia and
McMaster University Practice Guidelines pro-
vide clinicians and their patients with a basis
for rational decisions about the prophylaxis of
venous thromboembolism in medical patients
and long distance travelers. Clinicians, pa-
tients, third-party payers, institutional review
committees, other stakeholders, or the courts
should never view these recommendations as
dictates. As described in other guidelines fol-
lowing the GRADE approach, no guideline or
recommendation can take into account all of
the often-compelling unique features of indi-
vidual clinical circumstances. Therefore, no
one charged with evaluating clinicians’ actions
should attempt to apply the recommenda-
tions from these guidelines by rote or in a
blanket fashion.
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
Statements about the underlying values and
preferences, resources, feasibility, equity, ac-
ceptability as well as other qualifying remarks
accompanying each recommendation are its
integral parts and serve to facilitate an accu-
rate interpretation. They should never be
omitted when quoting or translating recom-
mendations from these guidelines if they in-
fluence the strength or direction of the rec-
ommendation.
Key questions
The following is a list of the clinical questions
selected by the Saudi expert panel and ad-
dressed in this guideline.
Thromboprophylaxis in acutely ill medical
patients
1. Should heparin versus no heparin be
used for prophylaxis of VTE in acutely
ill medical patients?
2. Should LMWH versus UFH be used for
prophylaxis of VTE in acutely ill medi-
cal patients?
3. Should extended duration (i.e., up to
30 or 40 days) versus a regular dura-
tion (i.e., up to 10 days) be used for
the thromboprophylaxis of VTE in
acutely ill hospitalized medical pa-
tients?
4. Should graduated compression stock-
ings (GCS) versus no GCS be used for
prophylaxis of VTE in acutely ill medi-
cal patients?
5. Should intermittent pneumatic com-
pression (IPC) versus no IPC be used
for prophylaxis of VTE in acutely ill
medical patients?
Thromboprophylaxis in critically ill medical
patients
6. Should heparin versus no heparin be
used for critically ill patients?
7. Should LMWH versus UFH be used for
critically ill patients?
8
8. Should graduated compression stock-
ings (GCS) versus no GCS be used for
critically ill patients?
9. Should intermittent pneumatic com-
pression (IPC) versus no IPC be used
for critically ill patients?
Thromboprophylaxis in chronically ill patients
10. Should thromboprophylaxis be used
for prophylaxis of VTE in chronically ill
medical patients?
Thromboprophylaxis in long distance travel-
ers
11. Should frequent ambulation be used
for long-distance travelers at in-
creased risk of VTE?
12. Should calf muscle exercise versus no
calf muscle exercise be used for
prophylaxis of VTE in long distance
travelers?
13. Should sitting in an aisle seat versus
no sitting in an aisle seat be used for
prophylaxis of VTE in long distance
travelers?
14. Should anticoagulants versus no anti-
coagulants be used for prophylaxis of
VTE in long distance travelers?
15. Should GCS versus no GCS be used for
prophylaxis of VTE in long distance
travelers?
Recommendations
Thromboprophylaxis in acutely ill medical
patients
Question 1: Should heparin versus no hepa-
rin be used for prophylaxis of VTE in acutely
ill medical patients?
Acutely ill medical patients are
Summary of Findings: We updated the 2014
systematic review by Alikhan et al1, but did
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
not identify new studies. The overall quality of
evidence was found to be low. The studies
included in the systematic review typically
defined acutely ill patients as patients hospi-
talized with acute medical illness (e.g. heart
failure, COPD), with a decrease in mobility.
Benefits of the option:
The meta-analysis of 6 trials (total of 5,944
participants) found very low quality evidence
of a reduction in deep venous thrombosis
(DVT) with the use of heparin compared to no
heparin for prophylaxis of DVT in acutely ill
hospitalized medical patients (OR 0.41; 95% CI
0.25 to 0.67; absolute effect for low risk pa-
tients: 1 fewer events per 1000; 95% CI 0-1;
absolute effect for high risk patients: 38 fewer
events per 1000; 95% CI 21-49).
The meta-analysis of 7 trials (total of 5939
participants) found low quality evidence of a
reduction in non-fatal pulmonary embolism
with the use of heparin compared to no hepa-
rin for prophylaxis of DVT in acutely ill hospi-
talized medical patients (OR 0.46; 95% CI 0.20
to 1.07; absolute effect in low risk patients: 1
fewer events per 1000; 95% CI 0-1; absolute
effect in high risk patients: 21 fewer events
per 1000 95% CI 3-31)
The meta-analysis of 8 trials (total of 27,980
participants) found low quality evidence that
did not rule out a reduction or an increase in
all-cause mortality with the use of heparin
compared to no heparin for prophylaxis of
DVT in acutely ill hospitalized medical patients
(OR 0.97; 95% CI 0.87 to 1.08; absolute effect:
1 fewer events per 1000; 95%CI 3-6).
Harms of the Option:
The meta-analysis of 8 trials (total of 13804
participants) found moderate quality evidence
of an increase in major bleeding with the use
of heparin compared to no heparin for
prophylaxis of DVT in acutely ill hospitalized
medical patients (OR 1.65; 95% CI 1.01 to
2.71; absolute effect: 2 more events per 1000
95% CI 0-6).
The meta-analysis of 6 trials (total of 13434
participants) found moderate quality evidence
9
of an increase in minor bleeding with the use
of heparin compared to no heparin for
prophylaxis of DVT in acutely ill hospitalized
medical patients (OR 1.61; 95% CI 1.26 to
2.08; absolute effect: 9 more events per 1000
95% CI 9-16).
The meta-analysis of 5 trials (total of 13349
participants) found moderate quality evidence
that did not rule out a reduction or an in-
crease in thrombocytopenia with the use of
heparin compared to no heparin for prophy-
laxis of DVT in acutely ill hospitalized medical
patients (OR 1.05; 95% CI 0.64 to 1.74; abso-
lute effect: 0 fewer events per 1000 95% CI 1-
3).
Resource Use: The panel judged the cost of
heparin to be low but to only be cost effective
in high-risk patients.
Feasibility, acceptability and equity considera-
tions: The panel judged the use of heparin for
the prophylaxis of VTE in acutely ill hospital-
ized medical patients to be both feasible and
acceptable by all relevant stakeholder groups
because of patient safety. The panel also
judged heparin in this population to unlikely
have an impact on health inequity.
Balance between desirable and undesirable
consequences: The panel judged the benefits
to clearly outweigh the harms in high-risk pa-
tients, but less clearly in low-risk patients. The
certainty of the evidence was considered to
be respectively moderate and low in high-risk
and low-risk patients. The panel judged the
intervention to be low-cost, cost effective (in
high-risk patients), feasible and acceptable.
Recommendation 1:
1a: In acutely ill hospitalized medical pa-
tients at high risk of VTE the panel recom-
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
10

mends heparin (UFH/LMWH) versus no 3. Impact of the implementation of

heparin for the prophylaxis of VTE. (strong guidelines on clinical practice.
recommendation, moderate quality evi- 4. Economic evaluation, including cost
dence) effectiveness.
5. Incidence of major bleeding in acutely
1b: In acutely ill hospitalized medical pa- ill hospitalized medical patients re-
tients at low risk of VTE the panel suggests ceiving heparin.
not using heparin for the prophylaxis of
VTE. (conditional recommendation, low
quality evidence) Question 2: Should low molecular weight
heparin versus unfractionated heparin be
Remarks: used for prophylaxis of VTE in acutely ill
 Risk stratification should be based on medical patients?
a validated risk stratification tool
(e.g., Padua Prediction Score)14 Summary of Findings: The findings are pri-
 Decision to provide thromboprophy- marily derived from a 2014 systematic review
laxis should consider the patients’ by Alikhan et al.1 The updated literature
risk of bleeding. search identified a 2013 randomized con-
trolled trial (RCT) by Ishi et al.16 The overall
quality of evidence was judged to be moder-
Subgroup considerations: Low risk and high-
ate.
risk acutely ill hospitalized medical patients as
described above.
Benefits and Harms of the Option: The meta-
analysis of 7 trials (total of 5983 participants)
Implementation considerations: Consider de-
found low quality evidence that did not rule
veloping and implementing a risk stratification
out a reduction or an increase in DVT with the
form.
use of LMWH compared to UFH for prophylax-
is of VTE in acutely ill hospitalized medical pa-
Monitoring and Evaluation:
tients (OR 0.86; 95% CI 0.39 to 1.9; absolute
1. Consider monitoring percentage of
effect: 1 fewer events per 1000; 95% CI 3-4).
patients for whom the risk stratifica-
tion form is completed.
The meta-analysis of 7 trials (total of 5485
2. Consider monitoring percentage of
participants) found low quality evidence that
acutely ill low risk medical patients
did not rule out a reduction or an increase in
receiving heparin thromboprophylax-
non-fatal pulmonary embolism with the use of
is.
LMWH compared to UFH for prophylaxis of
3. Consider monitoring percentage of
VTE in acutely ill hospitalized medical patients
acutely ill high risk medical patients
(OR 0.46; 95% CI 0.2 to 1.07; absolute effect:
receiving heparin thromboprophylax-
3 fewer events per 1000; 95% CI 0-4).
is.
The meta-analysis of 7 trials (total of 5605
Research Priorities: The panel highlighted the
participants) found moderate quality evidence
need for studies addressing the following re-
that did not rule out a reduction or an in-
search priorities in the KSA setting:
crease in all-cause mortality with the use of
1. Incidence of VTE in acutely ill hospital-
LMWH compared to UFH for prophylaxis of
ized medical patients.
VTE in acutely ill hospitalized medical patients
2. Values and preferences for giving
(OR 0.79; 95% CI 0.54 to 1.16; absolute effect:
heparin in different subgroups of
5 fewer events per 1000; 95% CI 3-10).
acutely ill medical patients.
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
The meta-analysis of 7 trials (total of 6028
participants) found moderate quality evidence
of a reduction in major bleeding with the use
of LMWH compared to unfractionated hepa-
rin for prophylaxis of VTE in acutely ill hospi-
talized medical patients (OR 0.39; 95% CI 0.2
to 0.73; absolute effect: 7 fewer events per
1000; 95% CI 3-9).
The meta-analysis of 4 trials (total of 3962
participants) found moderate quality evidence
of a reduction in minor bleeding with the use
of LMWH compared to UFH for prophylaxis of
VTE in acutely ill hospitalized medical patients
(OR 0.66; 95% CI 0.47 to 0.95; absolute effect:
13 fewer events per 1000; 95% CI 2-21).
The meta-analysis of 4 trials (total of 3962
participants) found moderate quality evidence
that did not rule out a reduction or an in-
crease in thrombocytopenia with the use of
LMWH compared to UFH for prophylaxis of
VTE in acutely ill hospitalized medical patients
(OR 0.34; 95% CI 0.08 to 1.45; absolute effect:
2 fewer events per 1000; 95% CI 1-3).
Resource Use: The panel judged there to be a
variation in cost across different hospital set-
tings and judged the nursing costs to higher
with UFH because it is given three times daily.
The panel judged LMWH to be cost effective.
Feasibility, acceptability and equity considera-
tions: The panel judged the use of LMWH for
prophylaxis of VTE in acutely ill hospitalized
medical patients to be both feasible and ac-
ceptable by patients and nurses. The panel
also judged LMWH in this population to un-
likely have an impact on health inequity.
Balance between desirable and undesirable
consequences: The panel judged the benefits
to probably outweigh the harms in acutely ill
medical patients. The certainty of the evi-
dence was considered to be low. The panel
judged LMWH to be probably cost effective,
feasible and acceptable.
Recommendation 2:
In acutely ill hospitalized medical patients
11
the panel suggests using LMWH versus UFH
for the prophylaxis of VTE. (conditional rec-
ommendation, low quality evidence)
Remark: In case of renal failure, use of UFH is
preferred
Implementation Considerations: Consider hav-
ing anti-factor Xa for LMWH monitoring made
available for pregnant and renal impairment
subpopulations.
Research Priorities: Consider conducting stud-
ies on cost effectiveness.
Question 3: Should extended duration (i.e.,
up to 30 or 40 days) versus a regular duration
(i.e., up to 10 days) be used for the thrombo-
prophylaxis of VTE in acutely ill hospitalized
medical patients?
The definition of extended duration thrombo-
prophylaxis is prophylaxis that is extends be-
yond the regular course of 10 days, and up to
30-40 days in total.
Summary of Findings: We updated the sys-
tematic review by Sharma et al9, but did not
identify new studies. The overall quality of
evidence was found to be moderate.
Benefits and Harms of the Option: The meta-
analysis of 3 trials (total of 20362 participants)
found moderate quality evidence of an in-
crease in major bleeding with the use of ex-
tended duration of thromboprophylaxis com-
pared to no extended duration of thrombo-
prophylaxis for acutely ill hospitalized medical
patients (RR 2.68; 95% CI 1.78 to 4.05; abso-
lute effect: 5 more events per 1000; 95% CI 2-
9).
The meta-analysis of 3 trials (total of 17542
participants) found moderate quality evidence
that did not rule out a reduction or an in-
crease in pulmonary embolism with the use of
extended duration of thromboprophylaxis
compared to no extended duration of throm-
boprophylaxis for acutely ill hospitalized med-
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
ical patients (RR 0.72; 95% CI 0.39 to 1.35;
absolute effect: 1 fewer events per 1000; 95%
CI 1-2).
The meta-analysis of 2 trials (total of 12552
participants) found moderate quality evidence
that did not rule out a reduction or an in-
crease in VTE- related mortality with the use
of extended duration of thromboprophylaxis
compared to no extended duration of throm-
boprophylaxis for acutely ill hospitalized med-
ical patients (RR 0.65; 95% CI 0.37 to 1.16;
absolute effect: 2 fewer events per 1000; 95%
CI 1-3).
The meta-analysis of 3 trials (total of 17547
participants) found moderate quality evidence
that did not rule out a reduction or an in-
crease in symptomatic DVT with the use of
extended duration of thromboprophylaxis
compared to no extended duration of throm-
boprophylaxis for acutely ill hospitalized med-
ical patients (RR 0.45; 95% CI 0.17 to 1.2; ab-
solute effect: 3 fewer events per 1000; 95% CI
1-4).
The meta-analysis of 3 trials (total of 16723
participants) found high quality evidence that
did not rule out a reduction or an increase in
all-cause mortality with the use of extended
duration of thromboprophylaxis compared to
no extended duration of thromboprophylaxis
for acutely ill hospitalized medical patients
(RR 1.07; 95% CI 0.93 to 1.24; absolute effect:
3 more events per 1000; 95% CI 3-10).
Resource Use: The panel judged the cost of
heparin to be probably high because of cost
required to educate patients and the cost of
the medication itself. The panel judged the
intervention to probably not be cost effective.
Feasibility, acceptability and equity considera-
tions: The panel judged the use of extended
duration of thromboprophylaxis to be proba-
bly not acceptable or feasible as health educa-
tors are needed. The panel also judged the
impact on health inequity to probably in-
crease due to opportunity and cost from
pocket.
12
Balance between desirable and undesirable
consequences: The panel judged the harms of
extended duration of thromboprophylaxis to
clearly outweigh its benefits in acutely ill hos-
pitalized patients. The certainty of the evi-
dence was considered to be moderate. The
panel judged the intervention to be probably
of high cost, not cost effective, not feasible
and not acceptable.
Recommendation 3:
In acutely ill hospitalized medical patients
the panel recommends a regular duration
(i.e., up to 10 days) versus an extended du-
ration (i.e., up to 30 or 40 days) for the
thromboprophylaxis of VTE. (strong recom-
mendation, moderate quality evidence)
Research Priorities:
1. Identify the medical subpopulations
that would benefit from extended
thromboprophylaxis
2. Identify a risk stratification tool
Question 4: Should GCS versus no GCS be
used for hospitalized medical patients?
Summary of Findings: Our systematic search
of the literature did not identify studies other
than a RCT by Muir et al17 and a 2009 RCT by
Dennis et al.7
Benefits and Harms of the Option: The find-
ings of 1 trial7 (total of 2518 participants)
found low quality evidence that did not rule
out a reduction or an increase in symptomatic
DVT (follow up: 1-30 days) with the use of GCS
compared to no GCS in hospitalized medical
patients (RR 0.91; 95% CI 0.63 to 1.29; abso-
lute effect in high risk patients: 0 fewer events
per 1000l 95% CI 0-1; absolute effect in low
risk patients 6 fewer per 1000; 95% CI 19-25).
The findings of 1 trial7 (total of
2518participants) found low quality evidence
that did not rule out a reduction or an in-
crease in pulmonary embolism (follow up: 1-
30 days) with the use of GCS compared to no
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
13

GCS in hospitalized medical patients (RR 0.65; dence was considered to be low. The panel
95% CI 0.33 to 1.31; absolute effect in high was uncertain about cost-effectiveness, and
risk patients: 1 fewer events per 1000; 95% CI judged the intervention to be probably feasi-
0-1; absolute effect in low risk patients: 14 ble and acceptable.
fewer per 1000; 95% CI 12-26).
Recommendation 4:
7,17
The meta-analysis of 2 trials (total of 2615
participants) found moderate quality evidence 4a: In acutely ill hospitalized medical pa-
that did not rule out a reduction or an in- tients at low risk of VTE the panel recom-
crease in mortality (follow up: 1-30 days) with
mends against using GCS for prophylaxis of
the use of GCS compared to no GCS in hospi-
talized medical patients (RR 1.06; 95% CI 0.94 VTE. (strong recommendation, low quality
to 1.2; absolute effect: 3 fewer events per evidence)
1000; 95% CI 3-9).
4b: In acutely ill hospitalized medical pa-
The findings of 1 trial7 (total of 2518 partici-
tients at high risk of VTE and bleeding (who
pants) found very low quality evidence of an
increase in Skin breaks/ulcers/blisters/skin cannot receive pharmacological prophylax-
necrosis (follow up: 1-30 days) with the use of is) the panel suggests using GCS for the
GCS compared to no GCS in hospitalized med- prophylaxis of VTE. (conditional recommen-
ical patients (RR 4.02; 95% CI 2.34 to 6.91; dation, low quality evidence)
absolute effect: 38 more events per 1000;
95% CI 17-75).
Remarks:
1. Consider monitoring for skin lesions
The findings of 1 trial7 (total of 2518 partici-
and ischemia
pants) found very low quality evidence that
2. Physician must ensure proper fitting
did not rule out a reduction or an increase in
Lower limb ischemia/amputation (follow up:
Implementation Considerations: The hospital
1-30 days) with the use of GCS compared to
should acquire different sizes of compression
no GCS in hospitalized medical patients (RR
stockings of high quality.
3.52; 95% CI 0.73 to 16.9; absolute effect: 4
more events per 1000; 95% CI 0-25).
Monitoring and Evaluations:
1. Consider hospitals monitoring adher-
Resource Use: The panel judged the cost of
ence to GCS use
GCS to be low. But there is no evidence on
2. Consider introducing the risk stratifi-
whether GCS is cost effective.
cation form for acutely ill medical pa-
tients
Feasibility, acceptability and equity considera-
3. Consider monitoring percentage of
tions: The panel judged the use of GCS to be
patients getting the risk stratification
probably feasible or acceptable. The panel
form completed
was uncertain of the impact of GCS use on
4. Consider monitoring percentage of
health inequity.
acutely ill low risk medical patients us-
ing GCS
Balance between desirable and undesirable
5. Consider monitoring percentage of
consequences: The panel judged the harms of
acutely ill high risk medical patients
GCS to outweigh the benefits in acutely ill
using GCS
hospitalized medical patients at low-risk of
VTE. They judged this balance to be uncertain
Research Priorities: More trials in non-stroke
in in acutely ill hospitalized medical patients
medical patients are needed.
at high-risk of VTE. The certainty of the evi-
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
Question 5: Should IPC versus no IPC be used
for hospitalized medical patients?
Summary of Findings: We updated a system-
atic review by Roderick et al., which was on
surgical patients and thus was considered as
indirect evidence18, but we did not identify
new studies. The overall quality of evidence
was found to be low.
Benefits and Harms of the Option: The meta-
analysis of 19 trials found moderate quality
evidence of a reduction in symptomatic DVT
(follow up of 30 days) with the use of IPC
compared to no IPC in hospitalized medical
patients (RR 0.43; 95% CI 0.32 to 0.58; abso-
lute effect in high risk patients: 1 fewer events
per 1000; 95% CI 0-1, absolute effect in low
risk patients 38 fewer per 1000; 95% CI 28-
46).
The meta-analysis of 8 trials found low quality
evidence that did not rule out a reduction or
an increase in PE (follow up of 30 days) with
the use of IPC compared to no IPC in hospital-
ized medical patients (RR 0.82; 95% CI 0.41 to
1.62; absolute effect in high risk patients: 0
fewer events per 1000; 95% CI 0-1, absolute
effect in low risk patients: 38 fewer per 1000;
95% CI 28-46).
The meta-analysis of 2 trials (total of 2518
participants) found low quality evidence that
could not estimate the absolute effect of IPC
use compared to no IPC use in hospitalized
medical patients.
There were no studies that reported Skin
breaks/ulcers/blisters/skin necrosis as an out-
come and therefore we could not estimate
the absolute effect of IPC use compared to no
IPC use in hospitalized medical patients rela-
tive to this outcome.
Resource Use: The panel judged the cost of
IPC to probably not be low and where uncer-
tain whether IPC use is cost effective because
of the lack of evidence.
14
Feasibility, acceptability and equity considera-
tions: The panel judged the use of IPC to be
probably feasible but feasibility may vary by
hospitals and that IPC is less acceptable for
patients. The panel judged the impact of IPC
use on health inequity to be probably in-
creased and noted that cost and availability
need to be considered.
Balance between desirable and undesirable
consequences: The panel judged the harms of
IPC/SCD to probably outweigh the benefits in
acutely ill hospitalized medical patients at
low-risk of VTE. The balance was uncertain in
patients at high-risk of VTE. The certainty of
the evidence was considered to be low. The
panel was uncertain about the cost effective-
ness and the acceptability of the intervention.
It judged the intervention to probably in-
crease inequity and to be probably feasible.
Recommendation 5:
5a: In acutely ill hospitalized medical pa-
tients at low risk of VTE the panel recom-
mends against using IPC/SCD for prophylax-
is of VTE. (conditional recommendation, low
quality evidence)
5b: In acutely ill hospitalized medical pa-
tients at high risk of VTE and bleeding (who
should not receive pharmacological prophy-
laxis) the panel suggests using IPC/ SCD for
the prophylaxis of VTE. (conditional recom-
mendation, low quality evidence)
Remarks: The choice between mechanical
prophylaxis options (GCS versus IPC/SCD) will
depend on the local availability and patient
preference.
Implementation Considerations: Administra-
tors considering the use of SCD, need to take
into account for both its capital and opera-
tional costs
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
Monitoring and evaluation:
1. Consider hospitals monitoring adher-
ence to IPC use
2. Consider introducing the risk stratifi-
cation form for acutely ill medical pa-
tients
3. Consider monitoring percentage of
patients getting the risk stratification
form completed
4. Consider monitoring percentage of
acutely ill low risk medical patients us-
ing IPC
5. Consider monitoring percentage of
acutely ill high risk medical patients
using IPC
6. Consider performing compressive US
of the lower extremity patients who
have been hospitalized for > 72 hours
without any prophylaxis for VTE.
Research Priorities:
1. Better evidence for benefits and
harms of IPC
2. Evidence regarding the need for
screening
Thromboprophylaxis in critically ill medi-
cal patients
Question 6: Should heparin versus placebo
be used for critically ill patients?
Summary of Findings: We updated a system-
atic review by Alhazzani et al2, but did not
identify new studies. The overall quality of
evidence was found to be low. In the system-
atic review, critically ill patients were defined
as those being cared for in an intensive care
unit (ICU) setting.
Benefits and Harms of the Option: The find-
ings of 1 trial (total of 1935 participants)
found moderate quality evidence that did not
rule out a reduction or an increase in symp-
tomatic DVT with the use of heparin com-
pared to placebo in critically ill patients (RR
0.86; 95% CI 0.59 to 1.25; absolute effect: 8
fewer events per 1000; 95% CI 15-24).
15
The meta-analysis of 2 trials (total of 2895
participants) found moderate quality evidence
of a reduction in PE with the use of heparin
compared to placebo in critically ill patients
(RR 0.52; 95% CI 0.28 to 0.97; absolute effect:
0 fewer events per 1000; 95% CI 1-14).
The meta-analysis of 2 trials (total of 2156
participants) found low quality evidence that
did not rule out a reduction or an increase in
major bleeding with the use of heparin com-
pared to placebo in critically ill patients (RR
0.82; 95% CI 0.56 to 1.21; absolute effect: 9
fewer events per 1000; 95% CI 10-22).
The meta-analysis of 2 trials (total of 2148
participants) found moderate quality evidence
that did not rule out a reduction or an in-
crease in ICU mortality with the use of heparin
compared to placebo in critically ill patients
(RR 0.89; 95% CI 0.78 to 1.02; absolute effect:
0 fewer events per 1000; 95% CI 6-24).
Resource Use: The panel judged the cost of
heparin to be small and to probably be cost
effective, as appropriate prophylaxis provides
better value in terms of costs and health gains
than routine screening for DVT.
Feasibility, acceptability and equity considera-
tions: The panel judged the use of heparin to
be both feasible and acceptable. The panel
were uncertain about the impact of heparin
on health inequity in critically ill patients.
Balance between desirable and undesirable
consequences: The panel judged the benefits
of heparin to probably outweigh the harms in
critically ill medical patients. The certainty of
the evidence was considered to be low. The
panel judged the intervention to be low-cost,
probably cost effective, feasible and accepta-
ble.
Recommendation 6:
In critically ill medical patients the panel
recommends heparin versus no heparin for
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
the prophylaxis of VTE. (strong recommen-
dation, low quality evidence)
Remark: Decision to provide thrombo-
prophylaxis should consider the patients’ risk
of bleeding
Implementation Considerations and Monitor-
ing:
1. Consider introducing the risk stratifi-
cation form for critically ill medical
patients
2. Consider monitoring percentage of
patients getting the risk stratification
form completed
3. Consider monitoring percentage of
critically ill medical patients receiving
heparin
Research Priorities: Conduct more research on
the critically ill patient population.
Question 7: Should LMWH versus UFH be
used for critically ill patients?
Summary of Findings: We updated a system-
atic review by Alhazzani et al2, but did not
identify new studies. The overall quality of
evidence was found to be moderate.
Benefits and Harms of the Option: The meta-
analysis of 2 trials (total of 4722 participants)
found moderate quality evidence that did not
rule out a reduction or an increase in symp-
tomatic DVT with the use of LMWH compared
to UFH in critically ill patients (RR 0.87; 95% CI
0.6 to 1.25; absolute effect: 3 fewer events
per 1000; 95% CI 6-10).
The meta-analysis of 2 trials (total of 4722
participants) found low quality evidence that
did not rule out a reduction or an increase in
PE with the use of LMWH compared to UFH in
critically ill patients (RR 0.62; 95% CI 0.39 to 1;
absolute effect: 7 fewer events per 1000; 95%
CI 0-12).
The meta-analysis of 3 trials (total of 4212
participants) found moderate quality evidence
16
that did not rule out a reduction or an in-
crease in major bleeding with the use of
LMWH compared to UFH in critically ill pa-
tients (RR 0.97; 95% CI 0.75 to 1.26; absolute
effect: 2 fewer events per 1000; 95% CI 13-
14).
The meta-analysis of 4 trials (total of 5184
participants) found moderate quality evidence
that did not rule out a reduction or an in-
crease in ICU mortality with the use of LMWH
compared to UFH in critically ill patients (RR
0.93; 95% CI 0.82 to 1.04; absolute effect: 12
fewer events per 1000; 95% CI 7-32).
Resource Use: The panel judged the cost of
LMWH to be small and to probably be cost
effective, as appropriate prophylaxis provides
better value in terms of costs and health gains
than routine screening for DVT (Sud et al.)
Feasibility, acceptability and equity considera-
tions: The panel judged the use of LMWH to
be both feasible and acceptable. The panel
were uncertain about the impact of LMWH on
health inequity in critically ill patients.
Balance between desirable and undesirable
consequences: The panel judged the benefits
of LMWH to probably outweigh the harms in
critically ill medical patients. The certainty of
the evidence was considered to be low. The
panel judged the intervention to be low-cost,
probably cost effective, feasible and accepta-
ble.
Recommendation 7:
In critically ill medical patients the panel
suggests LMWH versus UFH for the prophy-
laxis of VTE. (conditional recommendation,
low quality evidence)
Remark: In case of renal failure, use of UFH is
preferred
Implementation Considerations and Monitor-
ing: Consider having anti-factor Xa for LMWH
monitoring made available for pregnant and
renal impairment subpopulations.
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
Research Priorities: Consider conducting cost
effectiveness studies.
Question 8: Should GCS versus no GCS be
used for critically ill patients?
Summary of Findings: We identified a pro-
spective cohort study by Arabi et al4, and did
not identify any other new studies. The over-
all quality of evidence was found to be very
low.
Benefits and Harms of the Option: The find-
ings of 1 observational study (total of 569 par-
ticipants) found very low quality evidence that
did not rule out a reduction or an increase in
VTE with the use of GCS compared to no GCS
in critically ill patients (HR 1.04; 95% CI 0.59 to
2.04; absolute effect: 3 more events per
1000).
The findings of 1 observational study (total of
569 participants) found very low quality evi-
dence that did not rule out a reduction or an
increase in hospital mortality with the use of
GCS compared to no GCS in critically ill pa-
tients (HR 0.62; 95% CI 0.62 to 1.21; absolute
effect: 1 fewer event per 1000).
The findings of 1 trial (total of 2518 partici-
pants) found very low quality evidence that
did not rule out a reduction or an increase in
skin breaks/ ulcers/ blisters/ skin necrosis (fol-
low up: 30 days) with the use of GCS com-
pared to no GCS in critically ill patients (RR
1.06; 95% CI 1.2 to 1.26; absolute effect: 1
more event per 1000).
The findings of 1 trial (total of 2518 partici-
pants) found very low quality evidence that
did not rule out a reduction or an increase in
lower limb ischemia/amputation (follow up:
30 days) with the use of GCS compared to no
GCS in critically ill patients (RR 0.93; 95% CI
0.82 to 1.04; absolute effect: 4 more events
per 1000).
17
Resource Use: The panel judged the cost of
GCS to be small and to probably not be cost
effective, as appropriate prophylaxis provides
better value in terms of costs and health gains
than routine screening for DVT.19
Feasibility, acceptability and equity considera-
tions: The panel judged the use of GCS to
probably be both feasible and acceptable. The
panel were uncertain about the impact of
LMWH on health inequity in critically ill pa-
tients.
Balance between desirable and undesirable
consequences: The panel judged the harms of
GCS for prophylaxis of VTE to probably out-
weigh the benefits in critically ill medical pa-
tients. The certainty of the evidence was con-
sidered to be low. The panel judged the inter-
vention to be low-cost and probably feasible
and acceptable.
Recommendation 8:
8a: In critically ill medical patients the panel
suggests not using GCS for prophylaxis of
VTE. (conditional recommendation, very low
quality evidence)
8b: In critically ill medical patients at high
risk of bleeding and in whom pharmacologi-
cal prophylaxis is not feasible and in set-
tings where IPC is not available the panel
suggests using GCS for prophylaxis of VTE.
(conditional recommendation, very low qual-
ity evidence)
Remarks:
1. Consider monitoring for skin le-
sions and ischemia
2. Physician must ensure proper fit-
ting
3. Ensure appropriate use of GCS
(thigh length versus knee length)
Implementation Considerations: The hospital
should acquire different sizes of GCS of high
quality
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
Monitoring and Evaluation:
1. Consider hospitals monitoring adher-
ence to GCS use
2. Consider introducing the risk stratifi-
cation form for critically ill medical pa-
tients
3. Consider monitoring percentage of
patients getting the risk stratification
form completed
4. Consider monitoring percentage of
critically ill medical patients using GCS
Research Priorities:
1. Benefits and harms of the use of GCS
in ICU populations.
2. Cost effectiveness of GCS use in criti-
cally ill medical patients.
Question 9: Should IPC versus no IPC be used
for critically ill patients?
Summary of Findings: We identified a pro-
spective cohort study by Arabi et al 4, and did
not identify any other new studies. The over-
all quality of evidence was found to be very
low.
Benefits and Harms of the Option: The find-
ings from 1 study (total of 618 participants)
found very low quality evidence that showed
a reduction in VTE with the use of IPC com-
pared to no IPC use in critically ill patients (HR
0.45; 95% CI 0.22 to 0.95; absolute effect: 39
fewer events per 1000; 95% CI 3-56).
The findings from 1 study found very low
quality evidence that did not rule out a reduc-
tion or an increase in hospital mortality with
the use of IPC compared to no IPC in critically
ill patients (HR 0.92; 95% CI 0.68 to 1.24; ab-
solute effect: 1 fewer events per 1000; 95% CI
0.68-1.24).
There were no studies that reported Skin
breaks/ulcers/blisters/skin necrosis as an out-
come and therefore we could not estimate
the absolute effect of IPC use compared to no
IPC use in hospitalized medical patients rela-
tive to this outcome.
18
Resource Use: The panel judged the cost of
IPC to be small and to probably be cost effec-
tive, as appropriate prophylaxis provides bet-
ter value in terms of costs and health gains
than routine screening for DVT (Sud et al.)
Feasibility, acceptability and equity considera-
tions: The panel judged the feasibility of the
use of IPC may vary among hospitals across
the kingdom of Saudi Arabia and judged that
the intervention is probably acceptable. The
panel judged the impact of IPC on health in-
equity is probably increased due to cost and
availability.
Balance between desirable and undesirable
consequences: The panel judged the benefits
of IPC/SCD for the prophylaxis of VTE to prob-
ably outweigh the harms in critically ill medi-
cal patients who are bleeding, at high risk of
bleeding or at high risk of VTE receiving phar-
macological prophylaxis. The certainty of the
evidence was considered to be very low. The
panel judged the intervention to be low-cost,
probably cost effective and probably accepta-
ble.
Recommendation 9:
9a: In critically ill medical patients who are
bleeding or at high risk of bleeding, the
panel suggests using IPC/ SCD for the
prophylaxis of VTE. (conditional recommen-
dation, very low quality evidence)
9b: In critically ill medical patients at high
risk of VTE receiving pharmacological
prophylaxis the panel suggests adding IPC/
SCD for the prophylaxis of VTE. (conditional
recommendation, very low quality evidence)
Monitoring and Evaluation:
1. Consider hospitals monitoring adher-
ence to IPC use
2. Consider introducing the risk stratifi-
cation form for critically ill medical pa-
tients
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
3. Consider monitoring percentage of
patients getting the risk stratification
form completed
4. Consider monitoring percentage of
critically ill medical patients using IPC
Research Priorities:
1. Benefits and harms of the use of IPC
in ICU populations.
2. Cost effectiveness of IPC use in criti-
cally ill medical patients.
Thromboprophylaxis in chronically ill pa-
tients
Question 10: Should thromboprophylaxis be
used for Prophylaxis of DVT in chronically ill
medical patients?
Summary of Findings: Our literature search
did not identify any eligible trial.
Benefits and Harms of the Option: There were
no studies that reported prophylaxis of DVT,
PE, major bleeding, minor bleeding, thrombo-
cytopenia, and all-cause mortality as out-
comes and therefore we could not estimate
the absolute effect of thromboprophylaxis use
compared to no thromboprophylaxis use in
chronically ill medical patients.
Resource Use: The panel were uncertain
about the cost or cost effectiveness of throm-
boprophylaxis in chronically ill medical pa-
tients.
Feasibility, acceptability and equity considera-
tions: The panel judged the use of thrombo-
prophylaxis to probably not be feasible or ac-
ceptable in chronically ill medical patients.
The panel were uncertain about the impact of
thromboprophylaxis on health inequity in
chronically ill patients.
Balance between desirable and undesirable
consequences: The panel judged the harms of
prophylaxis to probably outweigh its benefits
in chronically ill medical patients. The certain-
19
ty of the evidence was considered to be very
low. The panel members were uncertain re-
garding the cost and cost effectiveness of the
intervention and judged it to probably be nei-
ther feasible nor acceptable.
Recommendation 10:
In chronically ill medical patients the panel
suggests not using versus using prophylaxis
for VTE. (conditional recommendation, very
low quality evidence).
Research Priorities: Trials testing the efficacy
and safety of thromboprophylaxis in chroni-
cally ill patients.
Thromboprophylaxis in Long Distance
Travelers
Question 11: Should frequent ambulation be
used for long-distance travelers at increased
risk of VTE?
Travelers who are at high risk of VTE are those
with one or more of the following risk factors:
previous VTE, active malignancy, recent sur-
gery or trauma, advanced age, severe obesity,
estrogen use, pregnancy, limited mobility, and
a thrombophilic disorder.
Summary of Findings: Our review did not
identify any eligible systematic review or eli-
gible trial. We identified one relevant case–
control study (The Multiple Environmental
and Genetic Assessment of risk factors for
venous thrombosis study) 20The study includ-
ed 11 033 individuals who had travelled for
more than four hour by air within the previ-
ous eight weeks, and assessed a number of
risk factors. The adjusted odds ratio for the
association between exercising during flight
and the risk of thrombosis was 1.2 (95% CI
0.6-2.6).
Benefits and Harms of the Option: Given the
nature of the available evidence, we could not
estimate the absolute effect of frequent am-
bulation compared to no frequent ambulation
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
in long-distance travelers at increased risk of
VTE. No potentially significant harm was iden-
tified.
Resource Use: The panel judged the cost of
frequent ambulation to be small and probably
cost effective for long-distance travelers at
increased risk of VTE.
Feasibility, acceptability and equity considera-
tions: The panel judged frequent ambulation
to probably be feasible and acceptable in
long-distance travelers at increased risk of
VTE. The panel were uncertain about the im-
pact of frequent ambulation on health inequi-
ty in long-distance travelers at increased risk
of VTE.
Balance between desirable and undesirable
consequences: The panel judged the benefits
of frequent ambulation for the prophylaxis of
VTE to probably outweigh the harms in long
distance travelers (>8hrs). The certainty of the
evidence was considered to be very low. The
panel judged the intervention to be low-cost,
probably cost effective, feasible and accepta-
ble.
Recommendation 11:
In long distance high-risk travelers (>8hrs)
the panel suggests frequent ambulation for
the prophylaxis of VTE. (conditional recom-
mendation, very low quality evidence).
Question 12: Should calf muscle exercise ver-
sus no calf muscle exercise be used for VTE in
long distance travelers?
Summary of Findings: Our review did not
identify an existing eligible systematic review
or eligible trial. As mentioned above, the Mul-
tiple Environmental and Genetic Assessment
of risk factors for venous thrombosis case–
control study found an adjusted odds ratio for
the association between exercising during
flight and the risk of thrombosis of 1.2 (95% CI
0.6-2.6)20.
20
Benefits and Harms of the Option: Given the
nature of the available evidence, we could not
estimate the absolute effect of calf muscles
exercises compared to no calf muscle exercise
for VTE prophylaxis in long-distance travelers.
No potentially significant harm was identified.
Feasibility, acceptability and equity considera-
tions: The panel judged calf muscle exercise to
probably be feasible and acceptable for VTE
prophylaxis in long-distance travelers. The
panel were uncertain about the impact of calf
muscle exercise on health inequity for VTE in
long-distance travelers.
Balance between desirable and undesirable
consequences: The panel judged the benefits
of calf muscle exercise for prophylaxis of VTE
to probably outweigh the harms in long dis-
tance travelers. The certainty of the evidence
was considered to be very low. The panel
judged the intervention to be feasible and
acceptable.
Recommendation 12:
In long distance high-risk travelers (>8hrs)
the panel suggests calf muscle exercise for
the prophylaxis of VTE. (conditional recom-
mendation, very low quality evidence).
Question 13: Should sitting in an aisle seat
versus no sitting in an aisle seat be used for
VTE in long distance travelers?
Summary of Findings: Our review did not
identify any eligible systematic review or eli-
gible trial. The Multiple Environmental and
Genetic Assessment of risk factors for venous
thrombosis case–control study found that
window seating compared to aisle seating was
associated with thrombosis (OR= 2.2; 95% CI
1.1-4.4).20
Benefits and Harms of the Option: Given the
nature of the available evidence, we could not
estimate the absolute effect of aisle seating
compared window for VTE prophylaxis in
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
long-distance travelers. No potentially signifi-
cant harm was identified.
Feasibility, acceptability and equity considera-
tions: The panel judged sitting in an aisle to
probably be feasible and acceptable for VTE
prophylaxis in long-distance travelers. The
panel were uncertain about the impact of sit-
ting in an aisle on health inequity for VTE in
long-distance travelers.
Balance between desirable and undesirable
consequences: The panel judged the benefits
of sitting in the aisle seat for the prophylaxis
of VTE to probably outweigh the harms in long
distance travelers. The certainty of the evi-
dence was considered to be very low. The
panel judged the intervention to be feasible
and acceptable.
Recommendation 13:
In long distance high-risk travelers (>8hrs)
the panel suggests sitting in an aisle seat for
the prophylaxis of VTE. (conditional recom-
mendation, very low quality evidence).
Question 14: Should anticoagulants versus
no anticoagulants be used for VTE in long
distance travelers?
Summary of Findings: We identified one trial
comparing LMWH, aspirin and no drug inter-
vention in 300 “high-risk” air travelers21. Par-
ticipants were scanned for asymptomatic DVT,
and there were 0 events in 82 individuals re-
ceiving LMWH, 3 events in 84 receiving aspir-
ing, and 4 events in 83 individuals in the con-
trol group. None of the reported events was a
symptomatic VTE.
Benefits and Harms of the Option: We could
not estimate the absolute effect of anticoagu-
lant use compared to no anticoagulant use for
VTE prophylaxis in long-distance travelers.
There is indirect evidence about the risk of
bleeding with anticoagulants.
21
Resource Use: The panel judged the cost of
anticoagulant use to be probably not small
and probably not cost effective for VTE
prophylaxis in long-distance travelers.
Feasibility, acceptability and equity considera-
tions: The panel judged anticoagulant use to
probably not be feasible and acceptable for
VTE prophylaxis in long-distance travelers. The
panel were uncertain about the impact of an-
ticoagulant use on health inequity for VTE in
long-distance travelers.
Balance between desirable and undesirable
consequences: The panel judged the benefits
of offering pharmacological thromboprophy-
laxis to probably outweigh the harms in long
distance travelers at increased risk of VTE. The
certainty of the evidence was considered to
be very low. The panel, however, judged the
intervention to be neither low-cost nor cost
effective. The panel also noted the interven-
tion may not be feasible or acceptable.
Recommendation 14:
In long distance travelers (>8hrs) at in-
creased risk of VTE, the panel suggests using
anticoagulants. (conditional recommenda-
tion, very low quality evidence).
Research Priorities: Consider conducting stud-
ies on efficacy and safety.
Question 15: Should GCS versus no GCS be
used for VTE in long distance travelers?
Summary of Findings: We updated a Cochrane
systematic review by Clarke et al22, but we did
not identify new studies.
Benefits and Harms of the Option: The meta-
analysis of 9 trials (total of 2637 participants)
found low quality evidence that could not es-
timate the relative risk of symptomatic DVT
with the use of GCS compared to no GCS in
long distance travelers (absolute effect: 0
fewer per 1000; 95% CI 1.5-1.5)
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
The meta-analysis of 9 trials (total of 2637
participants) found moderate quality evidence
that could not estimate the relative risk of PE
with the use of GCS compared to no GCS in
long distance travelers (absolute effect: 0
fewer per 1000; 95% CI 1.5-1.5
The meta-analysis of 9 trials (total of 2637
participants) found moderate quality evidence
that did not rule out a reduction or an in-
crease in Symptomless DVT with the use of
GCS compared to no GCS in long distance
travelers (RR 0.1; 95% CI 0.04 to 0.25; abso-
lute effect: 32 fewer events per 1000; 95% CI
27-34).
The meta-analysis of 9 trials (total of 2637
participants) found moderate quality evidence
that did not rule out a reduction or an in-
crease in Symptomless PE with the use of GCS
compared to no GCS in long distance travelers
(RR 0.1; 95% CI 0.04 to 0.25; absolute effect:
32 fewer events per 1000; 95% CI 27-34).
Resource Use: The panel judged the cost of
GCS to probably not be small and probably
not be cost effective for VTE prophylaxis in
long distance travelers.
22
Feasibility, acceptability and equity considera-
tions: The panel judged the use of GCS to
probably not be feasible or acceptable. The
panel were uncertain about the impact of GCS
on health inequity in long distance travelers.
Balance between desirable and undesirable
consequences: The panel judged the harms of
GCS for prevention of VTE to probably out-
weigh the benefits in long distance high-risk
travelers. The certainty of the evidence was
considered to be very low. The panel judged
the intervention to be of high cost and proba-
bly not cost effective. The panel also judged
the intervention to be neither feasible nor
acceptable.
Recommendation 15:
In long distance high-risk travelers (>8hrs)
the panel suggests not using GCS for the
prophylaxis of VTE. (conditional recommen-
dation, very low evidence).
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
23

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Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
26

Appendices
1. Appendix 1: Evidence-to-Decision Frameworks
2. Appendix 2: Search Strategies and Results
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
27

Appendix 1: Evidence to Decision Frameworks

Guideline Question 1: Should heparin versus no heparin be used for prophylaxis of DVT in acutely ill medical patients?

Problem: Acutely ill medical patients Background and Objective: More than 50% of VTE cases occur among patients hospitalized in medical wards.23-25
Option: Heparin Prophylaxis using heparin has been shown to reduce the incidence of VTE in hospitalized medical patients, but in-
Comparison: No heparin crease the incidence of bleeding.23
Setting: Inpatient
Perspective: The KSA MoH

Additional considera-
Criteria Research evidence
Judgements tions

No evidence specific to KSA identified

○ No
○ Probably no
Problem
Is there a problem
priority?
○ Uncertain
● Probably yes
○ Yes
○ Varies
The relative importance or values of the main outcomes of interest:
Is there important
○ Important
uncertainty or
Benefits & uncertainty about
variability Relative im- Certainty of the evidence
harms of how much people Outcome
portance (GRADE)
the options value the main out- ○ Possibly im-
comes? portant uncer- DVT Critical Very low
tainty or variabil-
ity
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
28

● Probably no PE Critical low

important uncer-
Major bleeding Critical moderate
tainty of variabil-
ity Minor Bleeding Important moderate
○ No important Thrombocytopenia Important moderate
uncertainty of
variability Mortality Important low
○ No known
undesirable
Summary of findings:
○ No included
studies Relative
What is the overall
certainty of this evi-
● Very low Outcome
Without
Heparin
With Hepa-
rin
Difference
(95% CI)
effect
(OR)
dence? ○ Low (95% CI)

○ Moderate 112/2931
(3.8%)
○ High 0.3% 6.7%
2 fewer per
1000 (from 1
fewer to 2 OR 0.41
● No (low risk) DVT fewer) (0.25 to
62 fewer per 0.67)
○ Probably no 1000 (from 34
11%
Are the desirable an-
ticipated effects
○ Uncertain fewer to 80
fewer)
large? ○ Probably yes
● Yes (high 1 fewer per
1000 (from 0
risk)
fewer to 1
OR 0.46
○ Varies PE
0.15% fewer)
(0.2 to
3.9% 21 fewer per
1.07)
1000 (from 3
○ No more to 31
Are the undesirable
anticipated effects ○ Probably no fewer)
small?
○ Uncertain Major bleeding
24/6710
(0.4%)
44/7094
(0.6%)
2 more per
1000 (from 0
OR 1.65
(1.01 to
○ Probably yes
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
29

● Yes fewer to 6 2.71)

more)
○ Varies
9 more per
OR 1.61
98/6525 193/6909 1000 (from 4
Minor Bleeding (1.26 to
(1.5%) (2.8%) more to 16
● No (low risk) more)
2.08)

○ Probably no 0 fewer per

OR 1.05
Are the desirable ef- 27/6479 38/6870 1000 (from 1
fects large relative to ○ Uncertain Thrombocytopenia
(0.4%) (0.6%) fewer to 3
(0.64 to
undesirable effects? 1.74)
○ Probably yes more)

● Yes (high risk) 717/14011

1 fewer per
1000 (from 3
OR 0.97
Mortality 4.5% (0.87 to
○ Varies (5.1%) more to 6
1.08)
fewer)

No evidence specific to KSA identified Resources required in

○ No Saudi Arabia are very
○ Probably no minute

Are the resources

required small?
○ Uncertain
○ Probably yes
● Yes
○ Varies
Resource
use No evidence specific to KSA identified
○ No
● Probably no
(low risk)
Is the incremental
cost small relative to ○ Uncertain
the net benefits?
● Probably yes
(high risk)
○ Yes
○ Varies
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
30

No evidence specific to KSA identified

○ Increased
○ Probably in-
creased

Equity
What would be the
impact on health in-
● Unlikely to
equities? affect equity
○ Probably re-
duced
○ Reduced
○ Varies
No evidence specific to KSA identified Acceptable by all rele-
○ No vant stakeholder groups
○ Probably no because of patient safety
and compliance by JCI
Is the option ac-
Acceptability ceptable to key ○ Uncertain
stakeholders?
○ Probably yes
● Yes
○ Varies
No evidence specific to KSA identified
○ No
○ Probably no
Feasibility
Is the option feasible
to implement?
○ Uncertain
○ Probably yes
● Yes
○ Varies
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
31

Recommendation
Should heparin versus no heparin be used for prophylaxis of DVT in acutely ill medical patients?
Undesirable consequences Undesirable consequences The balance between desira- Desirable consequences
Desirable consequences clearly
Balance of con- clearly outweigh desirable probably outweigh desirable ble and undesirable conse- probably outweigh undesir-
outweigh undesirable conse-
sequences consequences in most set- consequences in most set- quences is closely balanced or able consequences in most
quences in most settings
tings tings uncertain settings

○ ● (low risk) ○ ○ ● (high risk)

We recommend against We suggest not offering this We suggest offering this op-
Type of recommendation We recommend offering this option
offering this option option tion

○ ● (for patients at low risk of ○ ● (for patients at low risk of VTE)

VTE)

In acutely ill hospitalized medical patients at high risk of VTE the panel recommends heparin (UFH/LMWH) versus no heparin for the prophy-
laxis of VTE (strong recommendation, moderate quality evidence).

In acutely ill hospitalized medical patients at low risk of VTE the panel suggests not using heparin for the prophylaxis of VTE (conditional
Recommendation recommendation, low quality evidence).

Remarks:
 Risk stratification should be based on a validated risk stratification tool (e.g., Padua Prediction score)
 Decision to provide thromboprophylaxis should account for patients’ risk of bleeding

The panel judged the benefits to clearly outweigh the harms in high-risk patients, but less clearly in low-risk patients. The certainty of the
Justification evidence was considered to be respectively moderate and low in high-risk and low-risk patients. The panel judged the intervention to be low-
cost, cost effective (in high-risk patients), feasible and acceptable.

Subgroup considerations Low risk and high risk acutely ill hospitalized medical patients for VTE

Implementation considera-
Consider having a risk stratification form
tions

1. Consider monitoring percentage of patients for whom the risk stratification form is completed
Monitoring and evaluation 2. Consider monitoring percentage of acutely ill low risk medical patients receiving heparin thromboprophylaxis
3. Consider monitoring percentage of acutely ill high risk medical patients receiving heparin thromboprophylaxis

There is a need for studies addressing the following research priorities in the KSA setting:
Research possibilities 1. Incidence of VTE in acutely ill hospitalized medical patients
2. Values and preferences for giving heparin in different subgroups of acutely ill medical patients
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
32

3. Impact of the implementation of guidelines on clinical practice

4. Economic evaluation, including cost effectiveness
5. Incidence of major bleeding in acutely ill hospitalized medical patients receiving heparin
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
33

Evidence Profile: Heparin compared to no heparin for Prophylaxis of DVT in acutely ill medical patients
Bibliography (systematic reviews): Alikhan R, Bedenis R, Cohen AT. Heparin for the prevention of venous thromboembolism in acutely ill hospitalized medical patients (ex-
cluding stroke and myocardial infarction). Cochrane Database of Systematic Reviews 2014, Issue 5. Art. No.: CD003747

Quality assessment № of patients Effect

Quality Importance
№ of stud- Risk of Other considera- Relative Absolute
Study design Inconsistency Indirectness Imprecision Heparin no heparin
ies bias tions (95% CI) (95% CI)

Deep venous thrombosis

1 6 7 4
6 randomised not seri- serious serious serious none 112/2931 0.15% OR 0.41 1 fewer per 1000 (from 0 ⨁◯◯◯ Critical
trials ous (3.8%) (0.25 to fewer to 1 fewer) VERY LOW
0.67)
4
6.7% 38 fewer per 1000 (from
21 fewer to 49 fewer)

Non-Fatal pulmonary embolism

6 27 4
7 randomised not seri- not serious serious serious none 6/2920 (0.2%) 0.15% OR 0.46 1 fewer per 1000 (from 0 ⨁⨁◯◯ Critical
trials ous (0.2 to fewer to 1 fewer) LOW
1.07)
4
3.9% 21 fewer per 1000 (from 3
more to 31 fewer)

All-cause mortality
6 27 5
8 randomised not seri- not serious serious serious none 717/14011 4.5% OR 0.97 1 fewer per 1000 (from 3 ⨁⨁◯◯ Critical
trials ous (5.1%) (0.87 to more to 6 fewer) LOW
1.08)

Major bleeding
3
8 randomised not seri- not serious not serious serious none 44/7094 (0.6%) 24/6710 OR 1.65 2 more per 1000 (from 0 ⨁⨁⨁◯ Important
trials ous (0.4%) (1.01 to fewer to 6 more) MODERATE
2.71)

Minor bleeding
3
6 randomised not seri- not serious not serious serious none 193/6909 98/6525 OR 1.61 9 more per 1000 (from 4 ⨁⨁⨁◯ Important
trials ous (2.8%) (1.5%) (1.26 to more to 16 more) MODERATE
2.08)
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
34

Thrombocytopenia
2
5 randomised not seri- not serious not serious serious none 38/6870 (0.6%) 27/6479 OR 1.05 0 fewer per 1000 (from 1 ⨁⨁⨁◯ Important
trials ous (0.4%) (0.64 to fewer to 3 more) MODERATE
1.74)
MD – mean difference, RR – relative risk

1. Serious inconsistency. Unexplained heterogeneity, with point estimates widely different and confidence intervals not overlapping and leading to different conclu-
sions (I2= 59%)
2. Serious imprecision. 95% CI includes both estimates suggesting important benefit and estimates suggesting important harm.
3. Serious imprecision related to a total number of events less than 300
4. The baseline risks for DVT and PE outcomes for the low-risk and high-risk subgroups are based on a risk assessment model by Barbar et al. (J Thromb Haemost .
2010 ; 8 ( 11 ): 2450 - 2457)
5. The baseline risk for mortality is based on the findings of a systematic review by Dentali et al (Ann Internal Med. 2007;146(4):278-288.)
6. Serious indirectness. Patients included in the CLOTS trial (only stroke patients) differ from the PICO for this recommendation.
7. Serious imprecision for low risk patients (Low quality evidence); we judged the quality of evidence to be moderate in high risk patients

References:

1. Heit J A, S ilverstein M D, M ohr D N, P etterson T M, O’Fallon W M, M elton L J I II. R isk factors for deep vein thrombosis and pulmonary embolism: a
population-based case-control study . Arch Intern Med . 2000 ; 160 ( 6 ): 809 - 815 .
2. Decousus H , Tapson VF , Bergmann JF , et al ; IMPROVE Investigators. F actors at admission associated with bleeding risk in medical patients: fi ndings from
the IMPROVE investigators . Chest . 2011 ; 139 ( 1 ): 69 - 79 .
3. Anderson FA Jr, Wheeler HB, Goldberg RJ, et al. A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and
pulmonary embolism: the Worcester DVT Study. Arch Intern Med 1991;151:933-938. 4.
4. Goldhaber SZ, Dunn K, MacDougall RC. New onset of venous thromboembolism among hospitalized patients at Brigham and Women’s Hospital is caused more
often by prophylaxis failure than by withholding treatment. Chest 2000;118:1680-1684.
5. Goldhaber SZ, Tapson VF. A prospective registry of 5,451 patients with ultrasound-confirmed deep vein thrombosis. Am J Cardiol 2004;93:259-262.
6. Ishi, S. V., Lakshmi, M., Kakde, S. T., Sabnis, K. C., Jagannati, M., Girish, T. S., . . . Cherian, A. M. (2013). Randomised controlled trial for efficacy of unfractionated
heparin (UFH) versus low molecular weight heparin (LMWH) in thrombo-prophylaxis. Journal of the Association of Physicians of India, 61(12), 882-886.
7. Alikhan R, Bedenis R, Cohen AT. Heparin for the prevention of venous thromboembolism in acutely ill hospitalized medical patients (excluding stroke and
myocardial infarction). Cochrane Database of Systematic Reviews 2014, Issue 5. Art. No.: CD003747. DOI: 10.1002/14651858.CD003747.pub4.
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
35

Guideline Question 2: Should low molecular weight heparin versus unfractionated heparin be used for prophylaxis of VTE in acutely ill
medical patients?

Problem: Acutely ill medical patients
Option: Low molecular weight heparin
Comparison: Unfractionated heparin
Setting: Inpatient or outpatient
Perspective: The KSA MoH
Background and Objective: More than 50% of VTE cases occur among patients hospitalized in medical wards.23-25
Prophylaxis using heparin has been shown to reduce the incidence of VTE in hospitalized medical patients, but in-
crease the incidence of bleeding.23

Additional considera-
Criteria Judgements Research evidence
tions

No evidence specific to KSA identified

○ No
○ Probably no
Problem
Is there a problem ○ Uncertain
priority?
● Probably yes
○ Yes
○ Varies

The relative importance or values of the main outcomes of interest:

○ Important
uncertainty or Relative im- Certainty of the evidence
Outcome
Is there important variability portance (GRADE)
Benefits & uncertainty about
harms of how much people ○ Possibly im- Deep venous thrombosis Critical Low
the options value the main portant uncer-
outcomes? tainty or varia- Non-fatal pulmonary em-
Critical Low
bility bolism

○ Probably no All-cause mortality Important Moderate

important un-
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
36

Additional considera-
Criteria Judgements Research evidence
tions

certainty of
Major bleeding Critical Moderate
variability
○ No important Minor bleeding Important Moderate
uncertainty of Thrombocytopenia Important Moderate
variability
○ No known Summary of findings:
undesirable
With Low Relative
With Unfrac-
molecular Difference effect
Outcome tionated hepa-
weight (95% CI) (OR)
rin
heparin (95% CI)

○ No included Deep venous 13/2981 12/3002

1 fewer per
1000 (from
OR 0.86
studies (0.39 to
thrombosis (0.4%) (0.4%) 3 fewer to 4
1.9)
What is the overall
○ Very low more)

certainty of this ● Low 3 fewer per

OR 0.46
evidence? Non-fatal pulmo- 14/2565 6/2920 1000 (from
○ Moderate nary embolism (0.5%) (0.2%) 0 fewer to 4
(0.2 to
1.07)
fewer)
○ High
5 fewer per
OR 0.79
49/2798 1000 (from
All-cause mortality 62/2807 (2.2%) (0.54 to
(1.8%) 3 more to 10
1.16)
○ No fewer)

● Probably no 33/3026 12/3002

7 fewer per
1000 (from
OR 0.39
Are the desirable (PE and DVT) Major bleeding (0.2 to
(1.1%) (0.4%) 3 fewer to 9
0.73)
anticipated effects
large?
○ Uncertain fewer)

○ Probably yes 13 fewer per

OR 0.66
79/1986 53/1976 1000 (from
○ Yes Minor bleeding
(4.0%) (2.7%) 2 fewer to
(0.47 to
0.95)
21 fewer)
○ Varies
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
37

Additional considera-
Criteria Judgements Research evidence
tions

2 fewer per
OR 0.34
1/1976 1000 (from
Thrombocytopenia 6/1986 (0.3%) (0.08 to
(0.1%) 1 more to 3
1.45)
○ No fewer)

○ Probably no
○ Uncertain
Are the undesira-
ble anticipated
● Probably yes
effects small? (bleeding ef-
fects)
○ Yes
○ Varies

○ No
○ Probably no
Are the desirable
effects large rela-
○ Uncertain
tive to undesirable ● Probably yes
effects?
○ Yes
○ Varies

No evidence specific to KSA identified Cost of all to administer

Resource Are the resources

○ No
(Dr. Hasan: 19.83 rl: 40
use required small? ○ Probably no
○ Uncertain 15.4 rl: vial= 1 dose
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
38

Additional considera-
Criteria Judgements Research evidence
tions

Dr. Yousef: 4 $ )
● Probably yes
(LMWH) Variation in cost across
○ Yes different hospital settings/
nursing costs is higher with
○ Varies unfractionated heparin be-
cause tid

Actual cost unknown ( no

evidence)

No evidence specific to KSA identified

○ No
○ Probably no
Is the incremental
cost small relative
○ Uncertain
to the net bene- ● Probably yes
fits?
○ Yes
○ Varies

Unlikely to have any effect

○ Increased on equity
○ Probably
What would be the increased
Equity impact on health
inequities? ●
Uncertain

○ Probably
reduced
○ Reduced
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
39

Additional considera-
Criteria Judgements Research evidence
tions

○ Varies

No evidence specific to KSA identified 1. Patients

○ No 2. Nurses
○ Probably no
Is the option ac-
Acceptability ceptable to key
○ Uncertain
stakeholders? ● Probably yes
○ Yes
○ Varies

No evidence specific to KSA identified

○ No
○ Probably no
Feasibility
Is the option fea-
sible to imple-
○ Uncertain
ment? ● Probably yes
○ Yes
○ Varies
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
40

Recommendation
Should low molecular weight heparin versus Unfractionated heparin be used for Prophylaxis of VTE in acutely ill
medical patients?
Undesirable consequences Undesirable consequences Desirable consequences Desirable consequences
The balance between desirable
Balance of con- clearly outweigh desirable probably outweigh desirable probably outweigh undesira- clearly outweigh undesirable
and undesirable consequences
sequences consequences in most set- consequences in most set- ble consequences in most consequences in most set-
is closely balanced or uncertain
tings tings settings tings

○ ○ ○ ● ○
We recommend against of- We suggest not offering this We recommend offering this
Type of recommendation We suggest offering this option
fering this option option option

○ ○ ● ○

In acutely ill hospitalized medical patients the panel suggests using low molecular weight heparin versus unfractionated heparin for the
prophylaxis of VTE (conditional recommendation, low quality evidence)
Recommendation
Remark: In case of renal failure, use of unfractionated heparin is preferred

The panel judged the benefits to probably outweigh the harms in acutely ill medical patients. The certainty of the evidence was considered to
Justification
be low. The panel judged low molecular weight heparin to be probably cost effective, feasible and acceptable.

Subgroup considerations None

Implementation considera-
Consider having anti-factor Xa for LMWH monitoring made available for pregnant and renal impairment subpopulations.
tions

Monitoring and evaluation None

Research possibilities Cost effectiveness studies

Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
41

Evidence Profile: Low molecular weight heparin compared to unfractionated heparin for prophylaxis of VTE in acutely ill medical patients

Bibliography (systematic reviews): Alikhan R, Bedenis R, Cohen AT. Heparin for the prevention of venous thromboembolism in acutely ill hospitalized medical patients (ex-
cluding stroke and myocardial infarction). Cochrane Database of Systematic Reviews 2014, Issue 5. Art. No.: CD003747 Ishi, S. V., Lakshmi, M., Kakde, S. T., Sabnis, K. C.,
Jagannati, M., Girish, T. S., Cherian, A. M. (2013). Randomized controlled trial for efficacy of unfractionated heparin (UFH) versus low molecular weight heparin (LMWH) in
thrombo-prophylaxis. Journal of the Association of Physicians of India, 61(12), 882-886.

Quality assessment № of patients Effect

Quality Importance
№ of Risk of Other considera- Low molecular Unfractionated Relative Absolute
Study design Inconsistency Indirectness Imprecision
studies bias tions weight heparin heparin (95% CI) (95% CI)

Deep venous thrombosis

1 2
7 randomised not not serious serious serious none 12/3002 (0.4%) 13/2981 (0.4%) OR 0.86 1 fewer per 1000 (from 3 ⨁⨁◯◯ Critical
trials serious (0.39 to fewer to 4 more) LOW
1.9)

Non-fatal pulmonary embolism

1 2
7 randomised not not serious serious serious none 6/2920 (0.2%) 14/2565 (0.5%) OR 0.46 3 fewer per 1000 (from 0 ⨁⨁◯◯ Critical
trials serious (0.2 to fewer to 4 fewer) LOW
1.07)

All-cause mortality
2
randomised not not serious not serious serious none 49/2798 (1.8%) 62/2807 (2.2%) OR 0.79 5 fewer per 1000 (from 3 ⨁⨁⨁◯ Critical
trials serious (0.54 to more to 10 fewer) MODERATE
1.16)

Major bleeding
3
7 randomised not not serious not serious serious none 12/3002 (0.4%) 33/3026 (1.1%) OR 0.39 7 fewer per 1000 (from 3 ⨁⨁⨁◯ Important
trials serious (0.2 to fewer to 9 fewer) MODERATE
0.73)

Minor bleeding
3
4 randomised not not serious not serious serious none 53/1976 (2.7%) 79/1986 (4.0%) OR 0.66 13 fewer per 1000 (from 2 ⨁⨁⨁◯ Important
trials serious (0.47 to fewer to 21 fewer) MODERATE
0.95)
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
42

Thrombocytopenia
2
4 randomised not not serious not serious serious none 1/1976 (0.1%) 6/1986 (0.3%) OR 0.34 2 fewer per 1000 (from 1 ⨁⨁⨁◯ Important
trials serious (0.08 to more to 3 fewer) MODERATE
1.45)

MD – mean difference, RR – relative risk

1. Serious indirectness. Some of studies that contributed data for the pooled relative effect assessed asymptomatic events
2. Serious imprecision. 95% CI includes both estimates suggesting important benefit and estimates suggesting important harm.
3. Serious imprecision related to a total number of events less than 300

References:

1. Heit J A, S ilverstein M D, M ohr D N, P etterson T M, O’Fallon W M, M elton L J I II. R isk factors for deep vein thrombosis and pulmonary
embolism: a population-based case-control study . Arch Intern Med . 2000 ; 160 ( 6 ): 809 - 815 .
2. Decousus H , Tapson VF , Bergmann JF , et al ; IMPROVE Investigators. F actors at admission associated with bleeding risk in medical patients: fi
ndings from the IMPROVE investigators . Chest . 2011 ; 139 ( 1 ): 69 - 79 .
3. Anderson FA Jr, Wheeler HB, Goldberg RJ, et al. A population-based perspective of the hospital incidence and case-fatality rates of deep vein
thrombosis and pulmonary embolism: the Worcester DVT Study. Arch Intern Med 1991;151:933-938. 4.
4. Goldhaber SZ, Dunn K, MacDougall RC. New onset of venous thromboembolism among hospitalized patients at Brigham and Women’s Hospital is
caused more often by prophylaxis failure than by withholding treatment. Chest 2000;118:1680-1684.
5. Goldhaber SZ, Tapson VF. A prospective registry of 5,451 patients with ultrasound-confirmed deep vein thrombosis. Am J Cardiol 2004;93:259-262.
6. Ishi, S. V., Lakshmi, M., Kakde, S. T., Sabnis, K. C., Jagannati, M., Girish, T. S., . . . Cherian, A. M. (2013). Randomised controlled trial for efficacy of
unfractionated heparin (UFH) versus low molecular weight heparin (LMWH) in thrombo-prophylaxis. Journal of the Association of Physicians of India,
61(12), 882-886.
7. Alikhan R, Bedenis R, Cohen AT. Heparin for the prevention of venous thromboembolism in acutely ill hospitalized medical patients (excluding stroke
and myocardial infarction). Cochrane Database of Systematic Reviews 2014, Issue 5. Art. No.: CD003747. DOI: 10.1002/14651858.CD003747.pub4.
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
43

Guideline Question 3: Should extended duration (i.e., up to 30 or 40 days) versus a regular duration (i.e., up to 10 days) be used for the
thromboprophylaxis of VTE in acutely ill hospitalized medical patients?

Problem: Acutely ill hospitalized medical patients Background and Objective: Studies have shown an increased risk of venous thromboembolism in the first 30 days
Option: Extended duration of thromboprophylaxis (i.e., after patients’ discharge.9,26 It has been suggested that extended duration of thromboprophylaxis can reduce the risk
up to 30 or 40 days) of VTE after discharge.
Comparison: Regular duration of thromboprophy-
laxis (i.e., up to 10 days)
Setting: Inpatient or outpatient
Perspective: The KSA MoH

Additional con-
Criteria Judgements Research evidence
siderations

No evidence specific to KSA identified

○ No
○ Probably no
Problem
Is there a problem ○ Uncertain
priority?
● Probably yes
○ Yes
○ Varies
The relative importance or values of the main outcomes of interest:
○ Important
uncertainty or Outcome Relative importance Certainty of the evidence (GRADE)
Is there important variability
Benefits & uncertainty about Major bleeding Critical Moderate
harms of how much people ○ Possibly im-
portant uncer- PE Critical Moderate
the options value the main
outcomes? tainty or varia-
VTE-related mortality Critical Moderate
bility
● Probably no Symptomatic DVT Critical Moderate
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
44

Additional con-
Criteria Judgements Research evidence
siderations

important un-
All-cause mortality Important High
certainty of
variability
Summary of findings:
○ No important
uncertainty of Relative
no extended duration
variability Extended duration of Difference effect
Outcome of thromboprophy-
thromboprophylaxis (95% CI) (RR)
○ No known laxis
(95% CI)
undesirable
5 more per
RR 2.68
Major bleed- 1000 (from
○ No included ing
31/10206 (0.3%) 83/10156 (0.8%)
2 more to 9
(1.78 to
4.05)
studies more)
What is the over- ○ Very low 1 fewer per
all certainty of RR 0.72
this evidence? ○ Low PE 24/8838 (0.3%) 17/8704 (0.2%)
1000 (from
1 more to 2
(0.39 to
1.35)
● Moderate fewer)

○ High 2 fewer per

RR 0.65
VTE-related 1000 (from
30/6330 (0.5%) 19/6222 (0.3%) (0.37 to
mortality 1 more to 3
○ No fewer)
1.16)

● Probably no 3 fewer per

(DVT & PE) RR 0.45
Symptomatic 1000 (from
Are the desirable 42/8840 (0.5%) 20/8707 (0.2%) (0.17 to
anticipated effects ○ Uncertain DVT 1 more to 4
fewer)
1.2)
large?
○ Probably yes 3 more per
RR 1.07
○ Yes All-cause
357/8441 (4.2%) 379/8282 (4.6%)
1000 (from
(0.93 to
mortality 3 fewer to
○ Varies 10 more)
1.24)

Are the undesira-

○ No
ble anticipated ○ Probably no
effects small?
○ Uncertain
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
45

Additional con-
Criteria Judgements Research evidence
siderations

● Probably yes
○ Yes
○ Varies
● No
○ Probably no
Are the desirable
effects large rela- ○ Uncertain
tive to undesirable
effects? ○ Probably yes
○ Yes
○ Varies
No evidence specific to KSA identified Education on use
○ No and medication
● Probably no
Are the resources ○ Uncertain
required small?
○ Probably yes
○ Yes
Resource
○ Varies
use
No evidence specific to KSA identified
○ No
● Probably no
Is the incremental
cost small relative ○ Uncertain
to the net bene-
fits? ○ Probably yes
○ Yes
○ Varies
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
46

Additional con-
Criteria Judgements Research evidence
siderations

No evidence specific to KSA identified Opportunity cost/

○ Increased from pocket
● Probably
increased

Equity
What would be
the impact on
○ Uncertain
health inequities? ○ Probably
reduced
○ Reduced
○ Varies
No evidence specific to KSA identified
○ No
● Probably no
Is the option ac-
Acceptability ceptable to key
○ Uncertain
stakeholders? ○ Probably yes
○ Yes
○ Varies
No evidence specific to KSA identified Health educators
○ No
● Probably no
Feasibility
Is the option fea-
sible to imple-
○ Uncertain
ment? ○ Probably yes
○ Yes
○ Varies
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
47

Recommendation
Should extended duration (i.e., up to 30 or 40 days) versus a regular duration (i.e., up to 10 days) be used for the
thromboprophylaxis of VTE in acutely ill hospitalized medical patients?
Undesirable conse-
Undesirable conse- The balance between Desirable consequences
quences clearly out-
Balance of conse- quences probably out- desirable and undesirable probably outweigh un- Desirable consequences clearly outweigh
weigh desirable conse-
quences weigh desirable conse- consequences is closely desirable consequences undesirable consequences in most settings
quences in most set-
quences in most settings balanced or uncertain in most settings
tings

● ○ ○ ○ ○
We recommend against We suggest not offering We suggest offering this
Type of recommendation We recommend offering this option
offering this option this option option

● ○ ○ ○

In acutely ill hospitalized medical patients the panel recommends a regular duration (i.e., up to 10 days) versus an extended duration
Recommendation
(i.e., up to 30 or 40 days) for the thromboprophylaxis of VTE (strong recommendation, moderate quality evidence)

The panel judged the harms of extended duration of thromboprophylaxis to clearly outweigh its benefits in acutely ill hospitalized patients.
Justification The certainty of the evidence was considered to be moderate. The panel judged the intervention to be probably high-cost, not cost effec-
tive, not feasible and not acceptable.

Subgroup considerations None

Implementation considerations None

Monitoring and evaluation None

1. Identify the medical subpopulations that would benefit from extended thromboprophylaxis
Research possibilities
2. Identify a Risk stratification tool
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
48

Evidence Profile: Extended duration compared to regular duration for the thromboprophylaxis of VTE in acutely ill hospitalized medical patients

Bibliography (systematic reviews): Sharma A, Chatterjee S, Lichstein E, Mukherjee D. Extended thromboprophylaxis for medically ill patients with decreased mobility: does
it improve outcomes? J Thromb Haemost 2012; 10: 2053–60.

Quality assessment № of patients Effect

no extended duration Quality Importance

№ of Study de- Risk of Other consider- Extended duration of Relative Absolute
Inconsistency Indirectness Imprecision of thromboprophy-
studies sign bias ations thromboprophylaxis (95% CI) (95% CI)
laxis

Major bleeding
1
3 randomised not not serious not serious serious none 83/10156 (0.8%) 31/10206 (0.3%) RR 2.68 5 more per 1000 ⨁⨁⨁◯ Critical
trials serious (1.78 to (from 2 more to MODERATE
4.05) 9 more)

PE
1
3 randomised not not serious not serious serious none 17/8704 (0.2%) 24/8838 (0.3%) RR 0.72 1 fewer per ⨁⨁⨁◯ Critical
trials serious (0.39 to 1000 (from 1 MODERATE
1.35) more to 2 fewer)

VTE-related mortality
1
2 randomised not not serious not serious serious none 19/6222 (0.3%) 30/6330 (0.5%) RR 0.65 2 fewer per ⨁⨁⨁◯ Critical
trials serious (0.37 to 1000 (from 1 MODERATE
1.16) more to 3 fewer)

Symptomatic DVT
1
3 randomised not not serious not serious serious none 20/8707 (0.2%) 42/8840 (0.5%) RR 0.45 3 fewer per ⨁⨁⨁◯ Critical
trials serious (0.17 to 1000 (from 1 MODERATE
1.2) more to 4 fewer)

All-cause mortality

3 randomised not not serious not serious not serious none 379/8282 (4.6%) 357/8441 (4.2%) RR 1.07 3 more per 1000 ⨁⨁⨁⨁ Important
trials serious (0.93 to (from 3 fewer to HIGH
1.24) 10 more)

MD – mean difference, RR – relative risk

Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
49

1. Serious imprecision. 95% CI includes both estimates suggesting important benefit and estimates suggesting important harm; and a total number of events less
than 300.

References:

1. Heit J A, S ilverstein M D, M ohr D N, P etterson T M, O’Fallon W M, M elton L J I II. R isk factors for deep vein thrombosis and pulmonary
embolism: a population-based case-control study . Arch Intern Med . 2000 ; 160 ( 6 ): 809 - 815 .
2. Decousus H , Tapson VF , Bergmann JF , et al ; IMPROVE Investigators. F actors at admission associated with bleeding risk in medical patients: fi
ndings from the IMPROVE investigators . Chest . 2011 ; 139 ( 1 ): 69 - 79 .
3. Anderson FA Jr, Wheeler HB, Goldberg RJ, et al. A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis
and pulmonary embolism: the Worcester DVT Study. Arch Intern Med 1991;151:933-938. 4.
4. Goldhaber SZ, Dunn K, MacDougall RC. New onset of venous thromboembolism among hospitalized patients at Brigham and Women’s Hospital is caused
more often by prophylaxis failure than by withholding treatment. Chest 2000;118:1680-1684.
5. Goldhaber SZ, Tapson VF. A prospective registry of 5,451 patients with ultrasound-confirmed deep vein thrombosis. Am J Cardiol 2004;93:259-262.
6. Ishi, S. V., Lakshmi, M., Kakde, S. T., Sabnis, K. C., Jagannati, M., Girish, T. S., . . . Cherian, A. M. (2013). Randomised controlled trial for efficacy of
unfractionated heparin (UFH) versus low molecular weight heparin (LMWH) in thrombo-prophylaxis. Journal of the Association of Physicians of India,
61(12), 882-886.
7. Alikhan R, Bedenis R, Cohen AT. Heparin for the prevention of venous thromboembolism in acutely ill hospitalized medical patients (excluding stroke and
myocardial infarction). Cochrane Database of Systematic Reviews 2014, Issue 5. Art. No.: CD003747. DOI: 10.1002/14651858.CD003747.pub4.
8. Hull RD, Schellong SM, Tapson VF, Monreal M, Samama MM, Nicol P, Vicaut E, Turpie AG, Yusen RD. Extended-duration venous thromboembolism
prophylaxis in acutely ill hospitalized medical patients with recently reduced mobility: a randomized trial. Ann Intern Med 2010; 153: 8–18.
9. Rivaroxaban Compares Favorably with Enoxaparin in Preventing Venous Thromboembolism in Acutely Ill Patients Without Showing a Net Clinical Benefit.
Washington, DC: American College of Cardiology, 5 April 2011. http://www.cardiosource.org/News-Media/ Media-Center/News-
Releases/2011/04/MAGELLAN.aspx; accessed 15 January 2012.
10. Sharma, A., Chatterjee, S., Lichstein, E., & Mukherjee, D. (2012). Extended thromboprophylaxis for medically ill patients with decreased mobility:
does it improve outcomes?. Journal of Thrombosis and Haemostasis, 10(10), 2053-2060.
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
50

Guideline Question 4: Should GCS versus no GCS be used for hospitalized medical patients?

Problem: Hospitalized medical patients Background and Objective: Methods used for mechanical thromboprophylaxis include graduated compression
Option: GCS stockings (GCS), intermittent pneumatic compression (IPC) and venous foot pumps (VFPs). These methods work by
Comparison: No GCS increasing the velocity and volume of blood flow in the deep system by displacing blood from the superficial to the
Setting: Inpatient deep venous system through the perforating veins.27 These methods are of particular advantage for patients at high
Perspective: The KSA MoH risk of bleeding. However the evidence for using mechanical prophylaxis is derived mainly from trials conducted in
surgical patients.

Additional con-
Criteria Judgements Research evidence
siderations

No evidence specific to KSA identified

○ No
○ Probably no
Problem
Is there a problem ○ Uncertain
priority?
● Probably yes
○ Yes
○ Varies
The relative importance or values of the main outcomes of interest:
○ Important uncer-
tainty or variability Relative im- Certainty of the evi-
Outcome
portance dence (GRADE)
Is there important
○ Possibly im-
portant uncertainty Symptomatic DVT Critical low
Benefits & uncertainty about
or variability
harms of how much people PE Critical low
the options value the main out- ● Probably no im-
comes? portant uncertainty Mortality Important moderate
of variability
Skin breaks/ulcers/blisters/skin
Important Very low
○ No important necrosis
uncertainty of varia-
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
51

Additional con-
Criteria Judgements Research evidence
siderations

bility
Lower limb ischemia/amputation Important Very low
○ No known unde-
sirable
Summary of findings:
Relative
Difference effect
Outcome No GCS GCS
(95% CI) (RR)
○ No included stud- (95% CI)
ies
0 fewer per
What is the overall
certainty of this evi-
○ Very low 1000 (from
dence? ● Low 0 fewer to 1
fewer)
RR 0.91
○ Moderate Symptomatic DVT
0.15% 126/1256
(0.63 to
6.7% (10.0%) 6 fewer per
○ High 1000 (from
1.29)
19 more to
● No (low risk) 25 fewer)

○ Probably no 1 fewer per

Are the desirable

○ Uncertain 1000 (from
0 fewer to 1
anticipated effects ● Probably yes 0.15% 13/1256
fewer) RR 0.65
large? (high risk) PE (0.33 to
3.9% (1.0%)
14 fewer per 1.31)
○ Yes 1000 (from
○ Varies 12 more to
26 fewer)

3 more per RR 1.06

4.5%
○ No Mortality
131/1321 1000 (from (0.94 to
(9.9%) 3 fewer to 9 1.2)
Are the undesirable
anticipated effects
● Probably no more)
small? ○ Uncertain Skin 16/1262 64/1256 38 more per RR 4.02
breaks/ulcers/blisters/skin (1.3%) (5.1%) 1000 (from (2.34 to
○ Probably yes
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
52

Additional con-
Criteria Judgements Research evidence
siderations

○ Yes necrosis 17 more to 6.91)

75 more)
○ Varies
4 more per
RR 3.52
Lower limb ische- 2/1262 7/1256 1000 (from
● No (low risk) mia/amputation (0.2%) (0.6%) 0 fewer to
(0.73 to
16.9)
○ Probably no 25

Are the desirable

effects large relative
● Uncertain (high
risk)
to undesirable ef-
fects? ○ Probably yes
○ Yes
○ Varies
No evidence specific to KSA identified Low cost
○ No
○ Probably no
Are the resources ○ Uncertain
required small?
○ Probably yes
● Yes
Resource
○ Varies
use
No evidence specific to KSA identified
○ No
○ Probably no
Is the incremental
cost small relative to
● Uncertain
the net benefits? ○ Probably yes
○ Yes
○ Varies
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
53

Additional con-
Criteria Judgements Research evidence
siderations

No evidence specific to KSA identified

○ Increased
○ Probably in-
creased
What would be the
Equity impact on health in- ● Uncertain
equities?
○ Probably reduced
○ Reduced
○ Varies
No evidence specific to KSA identified
○ No
○ Probably no
Is the option ac-
Acceptability ceptable to key
○ Uncertain
stakeholders? ● Probably yes
○ Yes
○ Varies
No evidence specific to KSA identified
○ No
○ Probably no
Feasibility
Is the option feasible ○ Uncertain
to implement?
● Probably yes
○ Yes
○ Varies
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
54

Recommendation
Should GCS versus no GCS be used for prophylaxis of DVT in acutely ill medical patients?
Undesirable consequences Undesirable consequences The balance between desira- Desirable consequences
Desirable consequences clearly
Balance of con- clearly outweigh desirable probably outweigh desirable ble and undesirable conse- probably outweigh undesira-
outweigh undesirable conse-
sequences consequences in most set- consequences in most set- quences is closely balanced or ble consequences in most
quences in most settings
tings tings uncertain settings

● (low risk) ○ ● (high risk) ○ ○

We recommend against of- We suggest not offering this We suggest offering this op-
Type of recommendation We recommend offering this option
fering this option option tion

● (low risk) ○ ● (high risk) ○

In acutely ill hospitalized medical patients at low risk of VTE the panel recommends against using GCS for prophylaxis of VTE (strong recom-
mendation, low quality evidence).

In acutely ill hospitalized medical patients at high risk of VTE and bleeding (who should not receive pharmacological prophylaxis) the panel
Recommendation suggests using GCS for the prophylaxis of VTE (conditional recommendation, low quality evidence).

Remarks:
1. Consider monitoring for skin lesions and ischemia
2. Physician must ensure proper fitting

The panel judged the harms of GCS to outweigh the benefits in acutely ill hospitalized medical patients at low-risk of VTE. They judged this
Justification balance to be uncertain in in acutely ill hospitalized medical patients at high-risk of VTE. The certainty of the evidence was considered to be
low. The panel was uncertain about cost-effectiveness, and judged the intervention to be probably feasible and acceptable.

Subgroup considerations None

Implementation considera-  The hospital should acquire different sizes of compression stockings of high quality
tions

1. Consider hospitals monitoring adherence to GCS use

Monitoring and evaluation
2. Use similar to heparin considerations (monitor)

Research possibilities 1. More trials in non-stroke medical patients

Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
55

Evidence Profile: should GCS vs No GCS be used in hospitalized medical patients?

Bibliography (systematic reviews): Muir KW, Watt A, Baxter G, Grosset DG, Lees KR. Randomized trial of graded compression stocking for prevention of deep-vein throm-
bosis after acute stroke. QJM. 2000;93(6):359-364. Dennis M, Sandercock PA, Reid J, et al. The CLOTS Trials Collaboration. Effectiveness of thigh-length graduated compres-
sion stockings to reduce the risk of deep vein thrombosis after stroke (CLOTS trial 1): a multicenter, randomized controlled trial. Lancet . 2009;373(9679):1958-1965.

Quality assessment № of patients Effect

Quality Importance
№ of stud- Risk of Other considera- Relative Absolute
Study design Inconsistency Indirectness Imprecision GCS no GCS
ies bias tions (95% CI) (95% CI)

Symptomatic DVT (follow up: 1-30 days)

1 2 3
1 randomised not seri- not serious serious serious none 126/1256 0.15% RR 0.91 0 fewer per 1000 (from 0 ⨁⨁◯◯ Critical
trials ous (10.0%) (0.63 to 1.29) fewer to 1 fewer) LOW
3
6.7% 6 fewer per 1000 (from 19
more to 25 fewer)

PE (follow up: 1-30 days)

1 2 3
1 randomised not seri- not serious serious serious none 13/1256 0.15% RR 0.65 1 fewer per 1000 (from 0 ⨁⨁◯◯ Critical
trials ous (1.0%) (0.33 to 1.31) fewer to 1 fewer) LOW
3
3.9% 14 fewer per 1000 (from
12 more to 26 fewer)

Mortality (follow up: 30 days)

4 1 5
2 randomised not seri- not serious serious not serious none 131/1321 4.5% RR 1.06 3 more per 1000 (from 3 ⨁⨁⨁◯ Important
trials ous (9.9%) (0.94 to 1.2) fewer to 9 more) MODERATE

Skin breaks/ulcers/blisters/skin necrosis (follow up: 1-30 days)

6 1 7
1 randomised serious not serious serious serious none 64/1256 16/1262 RR 4.02 38 more per 1000 (from ⨁◯◯◯ Important
trials (5.1%) (1.3%) (2.34 to 6.91) 17 more to 75 more) VERY LOW

Lower limb ischemia/amputation (follow up: 1-30 days)

6 1 7
1 randomised serious not serious serious serious none 7/1256 2/1262 (0.2%) RR 3.52 4 more per 1000 (from 0 ⨁◯◯◯ Important
trials (0.6%) (0.73 to 16.9) fewer to 25 more) VERY LOW

MD – mean difference, RR – relative risk

Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
56

1. Serious indirectness. Patients included in the CLOTS trial (only stroke patients) differ from the PICO for this recommendation
2. Serious imprecision. 95% CI includes both estimates suggesting important benefit and estimates suggesting important harm
3. Baseline risk for DVT and PE subgroups (low-risk and high-risk populations) are derived from the risk assessment model by Barbar et al. (J Thromb Haemost . 2010 ;
8 ( 11 ): 2450 - 2457)
4. Data from CLOTS trial and Muir 2000
5. The baseline risks for DVT and PE outcomes for the low-risk and high-risk subgroups are based on a risk assessment model by Barbar et al. (J Thromb Haemost .
2010 ; 8 ( 11 ): 2450 - 2457)
6. Serious risk of bias. Studies that carried large weight for the overall effect estimate classified as high risk of bias due to lack of allocation concealment and lack of
blinding of outcome assessors
7. Serious imprecision. 95% CI includes both estimates suggesting important benefit and estimates suggesting important harm

References:

1. Heit J A, Silverstein M D, Mohr D N, Petterson T M, O’Fallon W M, Melton L J I II. Risk factors for deep vein thrombosis and pulmonary em-
bolism: a population-based case-control study . Arch Intern Med. 2000; 160 (6): 809 - 815.
2. Decousus H , Tapson VF , Bergmann JF , et al ; IMPROVE Investigators. F actors at admission associated with bleeding risk in medical patients:
findings from the IMPROVE investigators . Chest . 2011 ; 139 ( 1 ): 69 - 79 .
3. Anderson FA Jr, Wheeler HB, Goldberg RJ, et al. A population-based perspective of the hospital incidence and case-fatality rates of deep vein
thrombosis and pulmonary embolism: the Worcester DVT Study. Arch Intern Med 1991;151:933-938. 4.
4. Goldhaber SZ, Dunn K, MacDougall RC. New onset of venous thromboembolism among hospitalized patients at Brigham and Women’s Hospital is
caused more often by prophylaxis failure than by withholding treatment. Chest 2000;118:1680-1684.
5. Goldhaber SZ, Tapson VF. A prospective registry of 5,451 patients with ultrasound-confirmed deep vein thrombosis. Am J Cardiol 2004;93:259-262.
6. Ishi, S. V., Lakshmi, M., Kakde, S. T., Sabnis, K. C., Jagannati, M., Girish, T. S., Cherian, A. M. (2013). Randomised controlled trial for efficacy of un-
fractionated heparin (UFH) versus low molecular weight heparin (LMWH) in thrombo-prophylaxis. Journal of the Association of Physicians of India,
61(12), 882-886.
7. Benkö T , Cooke EA , McNally MA , Mollan RA . Graduated compression stockings: knee length or thigh length . Clin Orthop Relat Res .
2001 ; 383 ( 383 ): 197 - 203 .
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
57

Guideline Question 5: Should IPC versus no IPC be used for hospitalized medical patients?

Problem: Hospitalized medical patients Background and Objective: Methods used for mechanical thromboprophylaxis include graduated compression
Option: IPC stockings (GCS), intermittent pneumatic compression (IPC) and venous foot pumps (VFPs). These methods work by
Comparison: No IPC increasing the velocity and volume of blood flow in the deep system by displacing blood from the superficial to the
Setting: Inpatient deep venous system through the perforating veins.27 These methods are of particular advantage for patients at high
Perspective: The KSA MoH risk of bleeding. However the evidence for using mechanical prophylaxis is derived mainly from trials conducted in
surgical patients.

Additional con-
Criteria Judgements Research evidence
siderations

No evidence specific to KSA identified

○ No
○ Probably no
Is there a problem priori-
○ Uncertain
Problem
ty? ● Probably yes
○ Yes
○ Varies
The relative importance or values of the main outcomes of interest:
○ Important un-
certainty or varia- Relative im- Certainty of the evidence
Outcome
bility portance (GRADE)
Is there important uncer-
Benefits &
tainty about how much ○ Possibly im- Symptomatic
Critical Moderate
harms of portant uncertainty DVT
people value the main
the options or variability
outcomes?
PE Critical Low
● Probably no im-
portant uncertainty Death Important Low
of variability
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
58

Additional con-
Criteria Judgements Research evidence
siderations

○ No important Summary of findings:

uncertainty of vari-
ability Relative ef-
Difference (95%
Outcome No IPC IPC fect (RR)
○ No known unde- CI)
(95% CI)
sirable
1 fewer per
1000 (from 1
○ No included fewer to 1 few-
studies RR 0.43
Symptomatic 0.15% 112/1108 er)
(0.32 to
○ Very low DVT 6.7% (10.1%) 2 38 fewer per
1000 (from 28
0.58)
What is the overall cer-
tainty of this evidence? ● Low fewer to 46
fewer)
○ Moderate
0 fewer per
○ High 1000 (from 1
fewer to 1
RR 0.82
0.15% 22/1149 more)
PE (0.41 to
● No (low risk) 3.9% (1.9%) 7 fewer per
1000 (from 23
1.62)

○ Probably no fewer to 24
more)

Are the desirable antici-

○ Uncertain not esti- not estima- not estima-
pated effects large? ● Probably yes Death
mable ble
not estimable
ble
(high risk)
○ Yes
○ Varies
○ No
Are the undesirable an- ○ Probably no
ticipated effects small?
● Uncertain
○ Probably yes
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
59

Additional con-
Criteria Judgements Research evidence
siderations

○ Yes
○ Varies
○ No
● Probably no (low
risk)

Are the desirable effects ● Uncertain (high

large relative to undesir- risk)
able effects?
○ Probably yes
○ Yes
○ Varies
No evidence specific to KSA identified
○ No
● Probably no
Are the resources re- ○ Uncertain
quired small?
○ Probably yes
○ Yes
Resource
use
○ Varies
No evidence specific to KSA identified
○ No
Is the incremental cost
○ Probably no
small relative to the net ● Uncertain
benefits?
○ Probably yes
○ Yes
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
60

Additional con-
Criteria Judgements Research evidence
siderations

○ Varies
No evidence specific to KSA identified Consider availability
○ Increased & cost
● Probably in-
creased

Equity
What would be the im- ○ Uncertain
pact on health inequities?
○ Probably re-
duced
○ Reduced
○ Varies
No evidence specific to KSA identified Less acceptable for
○ No patients
○ Probably no
Acceptability
Is the option acceptable ● Uncertain
to key stakeholders?
○ Probably yes
○ Yes
○ Varies
No evidence specific to KSA identified Probably feasible
○ No may vary by hospi-
○ Probably no tals

Feasibility
Is the option feasible to ○ Uncertain
implement?
● Probably yes
○ Yes
○ Varies
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
61

Recommendation
Should IPC versus no IPC be used for prophylaxis of DVT in acutely ill medical patients?
Undesirable consequences Undesirable consequences The balance between desira- Desirable consequences
Desirable consequences clearly
Balance of con- clearly outweigh desirable probably outweigh desirable ble and undesirable conse- probably outweigh undesira-
outweigh undesirable conse-
sequences consequences in most set- consequences in most set- quences is closely balanced or ble consequences in most
quences in most settings
tings tings uncertain settings

● (low risk) ○ ● (high risk) ○ ○

We recommend against of- We suggest not offering this We suggest offering this op-
Type of recommendation We recommend offering this option
fering this option option tion

● (low risk) ○ ● (high risk) ○

In acutely ill hospitalized medical patients at low risk of VTE the panel recommends against using IPC/SCD for prophylaxis of VTE (condi-
tional recommendation, low quality evidence).

In acutely ill hospitalized medical patients at high risk of VTE and bleeding (who should not receive pharmacological prophylaxis) the panel
Recommendation
suggests using IPC/ SCD for the prophylaxis of VTE (conditional recommendation based on low quality evidence).

Remarks: The choice between mechanical prophylaxis options (GCS versus IPC/SCD) will depend on the local availability and patience pref-
erence

The panel judged the harms of IPC/SCD to probably outweigh the benefits in acutely ill hospitalized medical patients at low-risk of VTE. The
balance was uncertain in patients at high-risk of VTE. The certainty of the evidence was considered to be low. The panel was uncertain about
Justification
the cost effectiveness and the acceptability of the intervention. It judged the intervention to probably increase inequity and to be probably
feasible.

Subgroup considerations None

Implementation considera-
Administrators considering the use of SCD, need to take into account for both its capital and operational costs
tions

1. Consider introducing the risk stratification form for acutely ill medical patients
2. Consider monitoring percentage of patients getting the risk stratification form completed
Monitoring and evaluation
3. Consider monitoring percentage of acutely ill low risk medical patients using IPC
4. Consider monitoring percentage of acutely ill high risk medical patients using IPC

1. Better evidence for benefits and harms of IPC

Research possibilities
2. Evidence regarding the need for screening
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
62

Evidence Profile: IPC compared to no IPC for hospitalized medical patients

Bibliography (systematic reviews): Systematic review in surgical patients: Roderick P, Ferris G, Wilson K, et al. Toward evidence-based guidelines for the prevention of ve-
nous thromboembolism: systematic reviews of mechanical methods, oral anticoagulation, dextran and regional anesthesia as thromboprophylaxis. Health Technol Assess.
2005;9(49):1-78. Barbar S, Noventa F, Rossetto V, et al. A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism:
The Padua Prediction Score. J Thromb Haemost. 2010;8(11):2450-2457.

Quality assessment № of patients Effect

Quality Importance
№ of Risk of Other considera- Relative Absolute
Study design Inconsistency Indirectness Imprecision IPC no IPC
studies bias tions (95% CI) (95% CI)

Symptomatic DVT (follow up: 30 days)

1 2
19 randomised not seri- not serious serious not serious none 112/1108 0.15% RR 0.43 1 fewer per 1000 (from 1 ⨁⨁⨁◯ Critical
trials ous (10.1%) (0.32 to fewer to 1 fewer) MODERATE
0.58) 4
2
6.7% 38 fewer per 1000 (from
28 fewer to 46 fewer)

PE (follow up: 30 days)

4 5 2
8 randomised not seri- not serious serious serious none 22/1149 (1.9%) 0.15% RR 0.82 0 fewer per 1000 (from 1 ⨁⨁◯◯ Critical
trials ous (0.41 to fewer to 1 more) LOW
1.62) 3
2
3.9% 7 fewer per 1000 (from 23
fewer to 24 more)

Death
6 5
2 randomised not seri- not serious serious serious none not estima- not estimable ⨁⨁◯◯ Important
trials ous ble 7 LOW

Skin breaks/ulcers/blisters/skin necrosis - not reported

- - - - - - - - see com- not estimable see comment -

ment

MD – mean difference, RR – relative risk

1. Serious indirectness, given the RR for DVT is derived from studies of surgical patients (Roderick et al), which differ from the PICO for this recommendation
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
63

2. The baseline risks for DVT and PE outcomes for the low-risk and high-risk subgroups are based on a risk assessment model by Barbar et al. (J Thromb Haemost .
2010 ; 8 ( 11 ): 2450 - 2457)
3. Systematic review in surgical patients: Roderick P. Health Technol Assess. 2005;9(49):1-78. Systematic review in stroke patients: Naccarato M, Cochrane Database
Syst Rev. 2010;(8): Barbar 2010;8(11):2450-2457.
4. Serious indirectness, given the RR for PE is derived from studies of surgical patients (Roderick et al), which differ from the PICO for this recommendation. If IPCs
are used alone or as adjunct to anticoagulant/antiplatelet therapy, RR is 0.77 (0.41-1.43). This does not change the conclusions of this evidence profile.
5. Serious imprecision. 95% CI includes both estimates suggesting important benefit and estimates suggesting important harm.
6. Serious indirectness given the RR is derived from RCTs in stroke.
7. Naccarato M. Cochrane Database Syst Rev. 2010;(8): CD001922

References:

1. Heit J A, Silverstein M D, Mohr D N, Petterson T M, O’Fallon W M, Melton L J I II. Risk factors for deep vein thrombosis and pulmonary em-
bolism: a population-based case-control study . Arch Intern Med . 2000; 160 (6): 809 - 815.
2. Decousus H , Tapson VF , Bergmann JF , et al ; IMPROVE Investigators. F actors at admission associated with bleeding risk in medical patients:
findings from the IMPROVE investigators . Chest . 2011; 139 (1): 69 - 79.
3. Anderson FA Jr, Wheeler HB, Goldberg RJ, et al. A population-based perspective of the hospital incidence and case-fatality rates of deep vein
thrombosis and pulmonary embolism: the Worcester DVT Study. Arch Intern Med 1991;151:933-938. 4.
4. Goldhaber SZ, Dunn K, MacDougall RC. New onset of venous thromboembolism among hospitalized patients at Brigham and Women’s Hospital is
caused more often by prophylaxis failure than by withholding treatment. Chest 2000;118:1680-1684.
5. Goldhaber SZ, Tapson VF. A prospective registry of 5,451 patients with ultrasound-confirmed deep vein thrombosis. Am J Cardiol 2004;93:259-262.
6. Ishi, S. V., Lakshmi, M., Kakde, S. T., Sabnis, K. C., Jagannati, M., Girish, T. S., . . . Cherian, A. M. (2013). Randomised controlled trial for efficacy of un-
fractionated heparin (UFH) versus low molecular weight heparin (LMWH) in thrombo-prophylaxis. Journal of the Association of Physicians of India,
61(12), 882-886.
7. Benkö T , Cooke EA , McNally MA , Mollan RA . Graduated compression stockings: knee length or thigh length. Clin Orthop Relat Res. 2001;
383 (383): 197 - 203.
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
64

Guideline Question 6: Should Heparin versus Placebo be used for critically ill patients?

Problem: Critically ill patients Background and Objective: Hospitalized critically ill patients, especially ICU patients have several risk factors in-
Option: Heparin cluding sedating medications, the invasive procedures associated with their severe illness. Critically ill patients are
Comparison: Placebo also at high risk of bleeding.28 Studies suggest thromboprophylaxis with low molecular weight heparin or unfractionat-
Setting: ed heparin.29
Perspective: The KSA MoH

Additional con-
Criteria Judgements Research evidence
siderations

No evidence specific to KSA identified

○ No
○ Probably no
Is there a problem priori-
○ Uncertain
Problem
ty? ● Probably yes
○ Yes
○ Varies
The relative importance or values of the main outcomes of interest:
○ Important uncer-
tainty or variability Outcome Relative importance Certainty of the evidence (GRADE)

○ Possibly im- DVT Critical Moderate

portant uncertainty
Is there important uncer- PE Critical Moderate
Benefits & or variability
tainty about how much
harms of
the options
people value the main ● Probably no im- Major bleeding Critical Low
outcomes? portant uncertainty
ICU mortality Important Moderate
of variability
○ No important
uncertainty of vari-
ability
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
65

Additional con-
Criteria Judgements Research evidence
siderations

Summary of findings:
○ No known unde-
sirable
Relative ef-
Without With Hepa- Difference (95%
Outcome fect (RR)
Heparin rin CI)
(95% CI)
○ No included
studies 8 fewer per 1000 RR 0.86
56/959 49/976
DVT (from 15 more to (0.59 to
○ Very low (5.8%) (5.0%)
24 fewer) 1.25)
What is the overall cer-
tainty of this evidence? ● Low 9 fewer per 1000 RR 0.52
28/1434 15/1461
○ Moderate PE
(2.0%) (1.0%)
(from 1 fewer to
14 fewer)
(0.28 to
0.97)
○ High 9 fewer per 1000 RR 0.82
Major 53/1072 44/1084
(from 10 more to (0.56 to
bleeding (4.9%) (4.1%)
22 fewer) 1.21)
○ No
32 fewer per 1000 RR 0.89
○ Probably no ICU mor-
tality
313/1068
(29.3%)
283/1080
(26.2%)
(from 6 more to (0.78 to
64 fewer) 1.02)
Are the desirable antici-
○ Uncertain
pated effects large? ● Probably yes
○ Yes
○ Varies

○ No
○ Probably no
Are the undesirable antic- ○ Uncertain
ipated effects small?
● Probably yes
○ Yes
○ Varies
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
66

Additional con-
Criteria Judgements Research evidence
siderations

○ No
○ Probably no
Are the desirable effects ○ Uncertain
large relative to undesira-
ble effects?
● Probably yes
○ Yes
○ Varies
No evidence specific to KSA identified
○ No
○ Probably no
Are the resources re-
○ Uncertain
quired small? ○ Probably yes
● Yes
○ Varies
Resource
use
Appropriate prophylaxis provides better value in terms of costs and health gains
○ No than routine screening for DVT. Resources should be targeted at optimizing throm-
○ Probably no boprophylaxis.

Is the incremental cost ○ Uncertain

small relative to the net
benefits?
● Probably yes
○ Yes
○ Varies
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
67

Additional con-
Criteria Judgements Research evidence
siderations

No evidence specific to KSA identified

○ Increased
○ Probably in-
creased

Equity
What would be the impact
on health inequities?
● Uncertain
○ Probably reduced
○ Reduced
○ Varies
No evidence specific to KSA identified
○ No
○ Probably no
Acceptability
Is the option acceptable ○ Uncertain
to key stakeholders?
○ Probably yes
● Yes
○ Varies
No evidence specific to KSA identified
○ No
○ Probably no
Feasibility
Is the option feasible to ○ Uncertain
implement?
○ Probably yes
● Yes
○ Varies
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
68

Recommendation
Should heparin versus no heparin be used for critically ill patients?
Undesirable consequences Undesirable consequences Desirable consequences Desirable consequences
The balance between desirable
Balance of con- clearly outweigh desirable probably outweigh desirable probably outweigh undesira- clearly outweigh undesirable
and undesirable consequences
sequences consequences in most set- consequences in most set- ble consequences in most consequences in most set-
is closely balanced or uncertain
tings tings settings tings

● ○ ○ ○ ○
We recommend against of- We suggest not offering this We suggest offering this op-
Type of recommendation We recommend offering this option
fering this option option tion

● ○ ○ ○
Majority (3/4) of non-conflicted panelists voted for a strong recommendation

In critically ill medical patients the panel recommends heparin versus no heparin for the prophylaxis of VTE (strong recommendation, low
Recommendation quality evidence)

Remark: Decision to provide thromboprophylaxis should consider the patients’ risk of bleeding

The panel judged the benefits of heparin to probably outweigh the harms in critically ill medical patients. The certainty of the evidence was
Justification
considered to be low. The panel judged the intervention to be low-cost, probably cost effective, feasible and acceptable.

Subgroup considerations None

Implementation considera-
None
tions

1. Consider introducing the risk stratification form for acutely ill medical patients
2. Consider monitoring percentage of patients getting the risk stratification form completed
Monitoring and evaluation
3. Consider monitoring percentage of acutely ill low risk medical patients getting heparin
4. Consider monitoring percentage of acutely ill high risk medical patients getting heparin

Research possibilities 1. More research on this population

Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
69

Evidence Profile: Heparin compared to placebo for critically ill patients

Bibliography (systematic reviews): Alhazzani, W., Lim, W., Jaeschke, R. Z., Murad, M. H., Cade, J., & Cook, D. J. (2013). Heparin Thromboprophylaxis in Medical-Surgical
Critically Ill Patients: A Systematic Review and Meta-Analysis of Randomized Trials*. Critical care medicine, 41(9), 2088-2098.

Quality assessment № of patients Effect

Quality Importance
№ of Risk of Other considera- Relative Absolute
Study design Inconsistency Indirectness Imprecision Heparin Placebo
studies bias tions (95% CI) (95% CI)

Symptomatic DVT
4 12
1 randomised not seri- not serious not serious serious none 49/976 (5.0%) 56/959 (5.8%) RR 0.86 8 fewer per 1000 (from 15 ⨁⨁⨁◯ Critical
trials ous (0.59 to more to 24 fewer) MODERATE
1.25)

PE
12
3 randomised not seri- not serious not serious serious none 15/1461 28/1434 RR 0.52 9 fewer per 1000 (from 1 ⨁⨁⨁◯ Critical
trials ous (1.0%) (2.0%) (0.28 to fewer to 14 fewer) MODERATE
0.97)

Major bleeding
3 12
2 randomised not seri- serious not serious serious none 44/1084 53/1072 RR 0.82 9 fewer per 1000 (from 10 ⨁⨁◯◯ Critical
trials ous (4.1%) (4.9%) (0.56 to more to 22 fewer) LOW
1.21)

ICU mortality
2
2 randomised not seri- not serious not serious serious none 283/1080 313/1068 RR 0.89 32 fewer per 1000 (from 6 ⨁⨁⨁◯ Important
trials ous (26.2%) (29.3%) (0.78 to more to 64 fewer) MODERATE
1.02)

MD – mean difference, RR – relative risk

1. Serious imprecision related to a total number of events less than 300

2. Serious imprecision. 95% CI includes both estimates suggesting important benefit and estimates suggesting important harm
3. Serious inconsistency. Unexplained heterogeneity, with point estimates widely different and confidence intervals not overlapping and leading to different conclu-
sions (I2=50%)
4. Based on data from Shorr et al 2008
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
70

References:

1. Heit J A, Silverstein M D, Mohr D N, Petterson T M, O’Fallon W M, Melton L J I II. Risk factors for deep vein thrombosis and pulmonary em-
bolism: a population-based case-control study. Arch Intern Med . 2000; 160 (6): 809 - 815.
2. Decousus H , Tapson VF , Bergmann JF , et al ; IMPROVE Investigators. F actors at admission associated with bleeding risk in medical patients:
findings from the IMPROVE investigators . Chest . 2011 ; 139 ( 1 ): 69 - 79 .
3. Anderson FA Jr, Wheeler HB, Goldberg RJ, et al. A population-based perspective of the hospital incidence and case-fatality rates of deep vein
thrombosis and pulmonary embolism: the Worcester DVT Study. Arch Intern Med 1991;151:933-938. 4.
4. Goldhaber SZ, Dunn K, MacDougall RC. New onset of venous thromboembolism among hospitalized patients at Brigham and Women’s Hospital is
caused more often by prophylaxis failure than by withholding treatment. Chest 2000;118:1680-1684.
5. Goldhaber SZ, Tapson VF. A prospective registry of 5,451 patients with ultrasound-confirmed deep vein thrombosis. Am J Cardiol 2004;93:259-262.
6. Ishi, S. V., Lakshmi, M., Kakde, S. T., Sabnis, K. C., Jagannati, M., Girish, T. S., . . . Cherian, A. M. (2013). Randomised controlled trial for efficacy of un-
fractionated heparin (UFH) versus low molecular weight heparin (LMWH) in thrombo-prophylaxis. Journal of the Association of Physicians of India,
61(12), 882-886.
7. Hirsch DR, Ingenito EP, Goldhaber SZ: Prevalence of deep venous thrombosis among patients in medical intensive care. JAMA 1995;274:335–337.
8. Moser KM, LeMoine JR, Nachtwey FJ, et al: Deep venous thrombosis and pulmonary embolism. Frequency in a respiratory intensive care unit. JAMA
1981; 246:1422–1424.
9. Alhazzani, W., Lim, W., Jaeschke, R. Z., Murad, M. H., Cade, J., & Cook, D. J. (2013). Heparin Thromboprophylaxis in Medical-Surgical Critically Ill Pa-
tients: A Systematic Review and Meta-Analysis of Randomized Trials*. Critical care medicine, 41(9), 2088-2098.
10. Arnold DM, Donahoe L, Clarke FJ, et al: Bleeding during critical illness: A prospective cohort study using a new measurement tool. Clin Invest Med
2007; 30:E93–102.
11. Goldhaber SZ: Venous thromboembolism in the intensive care unit: The last frontier for prophylaxis. Chest 1998; 113:5–7
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
71

Guideline Question 7: Should LMWH versus UFH be used for critically ill patients?

Problem: Critically ill patients Background and Objective: Hospitalized critically ill patients, especially ICU patients have several risk factors in-
Option: LMWH cluding sedating medications, the invasive procedures associated with their severe illness. Critically ill patients are
Comparison: UFH also at high risk of bleeding.28 Studies suggest thromboprophylaxis with low molecular weight heparin or unfractionat-
Setting: ed heparin.29
Perspective: The KSA MoH

Additional consid-
Criteria Judgements Research evidence
erations

○ No No evidence specific to KSA identified

○ Probably no
Is there a problem pri- ○ Uncertain
Problem
ority?
● Probably yes
○ Yes
○ Varies
The relative importance or values of the main outcomes of interest:
○ Important uncer-
Relative im- Certainty of the evidence
tainty or variability Outcome
portance (GRADE)
Benefits &
Is there important un- ○ Possibly important
certainty about how Symptomatic
harms of uncertainty or varia- Critical Moderate
much people value the DVT
the options bility
main outcomes?
● Probably no im- PE Critical Low

portant uncertainty of Major bleeding Critical Moderate

variability
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
72

Additional consid-
Criteria Judgements Research evidence
erations

○ No important un- ICU mortality Important Moderate

certainty of variability

○ No known unde- Summary of findings:

sirable Relative
With Hepa- Difference
Outcome UFH effect (RR)
○ No included stud- rin (95% CI)
(95% CI)
ies
3 fewer per
RR 0.87
What is the overall cer-
○ Very low Symptomatic 60/2371 51/2351 1000 (from 6
(0.6 to
DVT (2.5%) (2.2%) more to 10 few-
tainty of this evidence? ● Low er)
1.25)

○ Moderate 7 fewer per

45/2371 28/2351 1000 (from 0 RR 0.62
○ High PE
(1.9%) (1.2%) fewer to 12 (0.39 to 1)
fewer)
○ No 2 fewer per
RR 0.97
○ Probably no Major bleed- 110/2102 107/2110 1000 (from 13
(0.75 to
ing (5.2%) (5.1%) fewer to 14
Are the desirable antic- ○ Uncertain more)
1.26)

ipated effects large?

● Probably yes 12 fewer per
RR 0.93
463/2597 424/2587 1000 (from 7
○ Yes ICU mortality
(17.8%) (16.4%) more to 32 few-
(0.82 to
1.04)
er)
○ Varies

Are the undesirable

○ No
anticipated effects ○ Probably no
small?
○ Uncertain
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
73

Additional consid-
Criteria Judgements Research evidence
erations

● Probably yes
○ Yes
○ Varies
○ No
○ Probably no
Are the desirable ef- ○ Uncertain
fects large relative to
undesirable effects? ● Probably yes
○ Yes
○ Varies
○ No No evidence specific to KSA identified

○ Probably no
Are the resources re- ○ Uncertain
quired small?
○ Probably yes
Resource ● Yes
use
○ Varies
Appropriate prophylaxis provides better value in terms of costs and health gains
Is the incremental cost
○ No than routine screening for DVT. Resources should be targeted at optimizing
Ref JAMA article
thromboprophylaxis. Fawler et al. (PRO-
small relative to the net ○ Probably no TECT)
benefits?
○ Uncertain
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
74

Additional consid-
Criteria Judgements Research evidence
erations

● Probably yes
○ Yes
○ Varies
○ Increased No evidence specific to KSA identified

○ Probably increased
What would be the im- ● Uncertain
Equity pact on health inequi-
ties? ○ Probably reduced
○ Reduced
○ Varies
○ No No evidence specific to KSA identified

○ Probably no
Is the option accepta- ○ Uncertain
Acceptability ble to key stakehold-
ers? ○ Probably yes
● Yes
○ Varies
○ No No evidence specific to KSA identified
Is the option feasible to
Feasibility
implement?
○ Probably no
○ Uncertain
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
75

Additional consid-
Criteria Judgements Research evidence
erations

○ Probably yes
● Yes
○ Varies
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
76

Recommendation
Should LMWH versus UFH be used for critically ill patients?
Undesirable consequences Undesirable consequences Desirable consequences Desirable consequences
The balance between desirable
Balance of con- clearly outweigh desirable probably outweigh desirable probably outweigh undesira- clearly outweigh undesirable
and undesirable consequences
sequences consequences in most set- consequences in most set- ble consequences in most consequences in most set-
is closely balanced or uncertain
tings tings settings tings

○ ○ ○ ● ○
We recommend against of- We suggest not offering this We suggest offering this op-
Type of recommendation We recommend offering this option
fering this option option tion

○ ○ ● ○
In critically ill medical patients the panel suggests LMWH versus UFH for the prophylaxis of VTE (conditional recommendation, low quality
evidence)
Recommendation
Remark: In case of renal failure, use of UFH is preferred

The panel judged the benefits of LMWH to probably outweigh the harms in critically ill medical patients. The certainty of the evidence was
Justification
considered to be low. The panel judged the intervention to be low-cost, probably cost effective, feasible and acceptable.

Subgroup considerations None

Implementation considera-
Consider having anti-factor Xa for LMWH monitoring made available for pregnant and renal impairment subpopulations.
tions

Monitoring and evaluation None

Research possibilities 1. Cost effectiveness

Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
77

Evidence Profile: LMWH compared to UFH for critically ill patients

Bibliography (systematic reviews): Alhazzani, W., Lim, W., Jaeschke, R. Z., Murad, M. H., Cade, J., & Cook, D. J. (2013). Heparin Thromboprophylaxis in Medical-Surgical
Critically Ill Patients: A Systematic Review and Meta-Analysis of Randomized Trials*. Critical care medicine, 41(9), 2088-2098.

Quality assessment № of patients Effect

Quality Importance
№ of Risk of Other considera- Relative Absolute
Study design Inconsistency Indirectness Imprecision LMWH UFH
studies bias tions (95% CI) (95% CI)

Symptomatic DVT
1
2 randomised not seri- not serious not serious serious none 51/2351 60/2371 RR 0.87 3 fewer per 1000 (from 6 ⨁⨁⨁◯ Critical
trials ous (2.2%) (2.5%) (0.6 to more to 10 fewer) MODERATE
1.25)

PE
2 1
2 randomised not seri- serious not serious serious none 28/2351 45/2371 RR 0.62 7 fewer per 1000 (from 0 ⨁⨁◯◯ Critical
trials ous (1.2%) (1.9%) (0.39 to 1) fewer to 12 fewer) LOW

Major bleeding
1
3 randomised not seri- not serious not serious serious none 107/2110 110/2102 RR 0.97 2 fewer per 1000 (from 13 ⨁⨁⨁◯ Critical
trials ous (5.1%) (5.2%) (0.75 to fewer to 14 more) MODERATE
1.26)

ICU mortality
1
4 randomised not seri- not serious not serious serious none 424/2587 463/2597 RR 0.93 12 fewer per 1000 (from 7 ⨁⨁⨁◯ Important
trials ous (16.4%) (17.8%) (0.82 to more to 32 fewer) MODERATE
1.04)

MD – mean difference, RR – relative risk

1. Serious imprecision. 95% CI includes both estimates suggesting important benefit and estimates suggesting important harm
2. Serious inconsistency. Unexplained heterogeneity, with point estimates widely different and confidence intervals not overlapping and leading to different conclu-
sions (I2=53%)
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
78

References:
1. Heit J A, Silverstein M D, Mohr D N, Petterson T M, O’Fallon W M, Melton L J I II. Risk factors for deep vein thrombosis and pulmonary em-
bolism: a population-based case-control study. Arch Intern Med . 2000; 160 (6): 809 - 815.
2. Decousus H, Tapson VF, Bergmann JF, et al ; IMPROVE Investigators. F actors at admission associated with bleeding risk in medical patients:
findings from the IMPROVE investigators. Chest. 2011; 139 (1): 69 - 79.
3. Anderson FA Jr, Wheeler HB, Goldberg RJ, et al. A population-based perspective of the hospital incidence and case-fatality rates of deep vein
thrombosis and pulmonary embolism: the Worcester DVT Study. Arch Intern Med 1991;151:933-938.
4. Goldhaber SZ, Dunn K, MacDougall RC. New onset of venous thromboembolism among hospitalized patients at Brigham and Women’s Hospital is
caused more often by prophylaxis failure than by withholding treatment. Chest 2000;118:1680-1684.
5. Goldhaber SZ, Tapson VF. A prospective registry of 5,451 patients with ultrasound-confirmed deep vein thrombosis. Am J Cardiol 2004;93:259-262.
6. Ishi, S. V., Lakshmi, M., Kakde, S. T., Sabnis, K. C., Jagannati, M., Girish, T. S., . . . Cherian, A. M. (2013). Randomised controlled trial for efficacy of un-
fractionated heparin (UFH) versus low molecular weight heparin (LMWH) in thrombo-prophylaxis. Journal of the Association of Physicians of India,
61(12), 882-886.
7. Hirsch DR, Ingenito EP, Goldhaber SZ: Prevalence of deep venous thrombosis among patients in medical intensive care. JAMA 1995;274:335–337.
8. Moser KM, LeMoine JR, Nachtwey FJ, et al: Deep venous thrombosis and pulmonary embolism. Frequency in a respiratory intensive care unit. JAMA
1981; 246:1422–1424.
9. Alhazzani, W., Lim, W., Jaeschke, R. Z., Murad, M. H., Cade, J., & Cook, D. J. (2013). Heparin Thromboprophylaxis in Medical-Surgical Critically Ill Pa-
tients: A Systematic Review and Meta-Analysis of Randomized Trials*. Critical care medicine, 41(9), 2088-2098.
10. Arnold DM, Donahoe L, Clarke FJ, et al: Bleeding during critical illness: A prospective cohort study using a new measurement tool. Clin Invest Med
2007; 30:E93–102.
11. Goldhaber SZ: Venous thromboembolism in the intensive care unit: The last frontier for prophylaxis. Chest 1998; 113:5–7
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
79

Guideline Question 8: Should GCS versus no GCS be used for critically ill patients?

Problem: Critically ill patients Background and Objective: Many trials have recommended the use of pharmacologic prophylaxis for critically ill
Option: GCS patients.29,30 However limited data exists on the use of mechanical thromboprophylaxis including IPC and GCS.4,31,32
Comparison: GCS
Setting:
Perspective: The KSA MoH

Additional con-
Criteria Judgements Research evidence
siderations

○ No No evidence specific to KSA identified

○ Probably no
Is there a problem ○ Uncertain
Problem
priority?
● Probably yes
○ Yes
○ Varies

The relative importance or values of the main outcomes of interest:

○ Important
Is there important
uncertainty or
Benefits & uncertainty about Relative im- Certainty of the evi-
variability Outcome
harms of how much people portance dence (GRADE)
the options value the main out- ○ Possibly im-
comes? portant uncer-
VTE Critical Very Low
tainty or variabil-
ity
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
80

Additional con-
Criteria Judgements Research evidence
siderations

● Probably no Hospital mortality Important Very Low

important uncer-
tainty of variabil-
Skin
ity Important Very Low
breaks/ulcers/blisters/skin necrosis
○ No important
uncertainty of Lower limb ischemia/amputation Important Very Low
variability

○ No known
undesirable
Summary of findings:

○ No included Relative
Without Difference effect
studies Outcome With GCS
GCS (95% CI) (RR)
What is the overall ● Very low (95% CI)
certainty of this evi-
dence? ○ Low
3 more per HR 1.04
○ Moderate 28/389 18/180 1000 (from
VTE
○ High (7.2%) (10.0%) 29 fewer to
69 more)
(0.59 to
2.04)

○ No 1 fewer per HR 0.86

Not esti- Not esti- 1000 (from 0
Hospital mortality
Are the desirable ● Probably no mated mated fewer to 0 (0.62 to
anticipated effects fewer) 1.21)
large? ○ Uncertain
○ Probably yes Skin 1 more per RR 1.06
16/1262 64/1256
breaks/ulcers/blisters/skin 1000 (from 1
○ Yes
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
81

Additional con-
Criteria Judgements Research evidence
siderations

○ Varies necrosis (1.3%) (5.1%) fewer to 3 (0.94 to

more) 1.2)

○ No 4 more per RR 3.52

Lower limb ische- 2/1262 7/1256 1000 (from 0
● Probably no mia/amputation (0.2%) (0.6%) fewer to 25 (0.73 to
Are the undesirable ○ Uncertain more) 16.9)
anticipated effects
small? ○ Probably yes
○ Yes
○ Varies

○ No
● Probably no
Are the desirable
effects large relative ○ Uncertain
to undesirable ef-
fects?
○ Probably yes
○ Yes
○ Varies

Resource Are the resources

○ No No evidence specific to KSA identified
use required small? ○ Probably no
○ Uncertain
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
82

Additional con-
Criteria Judgements Research evidence
siderations

○ Probably yes
● Yes
○ Varies

Appropriate prophylaxis provides better value in terms of costs and health gains than routine
○ No screening for DVT. Resources should be targeted at optimizing thromboprophylaxis.
● Probably no
Is the incremental ○ Uncertain
cost small relative to
the net benefits? ○ Probably yes
○ Yes
○ Varies

○ Increased No evidence specific to KSA identified

○ Probably in-
creased
What would be the ● Uncertain
Equity impact on health in-
equities? ○ Probably re-
duced

○ Reduced
○ Varies
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
83

Additional con-
Criteria Judgements Research evidence
siderations

○ No No evidence specific to KSA identified

○ Probably no
Is the option ac- ○ Uncertain
Acceptability ceptable to key
stakeholders? ● Probably yes
○ Yes
○ Varies

○ No No evidence specific to KSA identified

○ Probably no
Is the option feasible ○ Uncertain
Feasibility
to implement?
● Probably yes
○ Yes
○ Varies
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
84

Recommendation
Should GCS versus no GCS be used for critically ill patients?
Undesirable consequences Undesirable consequences Desirable consequences Desirable consequences
The balance between desirable
Balance of con- clearly outweigh desirable probably outweigh desirable probably outweigh undesira- clearly outweigh undesirable
and undesirable consequences
sequences consequences in most set- consequences in most set- ble consequences in most consequences in most set-
is closely balanced or uncertain
tings tings settings tings

○ ● ○ ○ ○
We recommend against of- We suggest not offering this We suggest offering this op-
Type of recommendation We recommend offering this option
fering this option option tion

○ ● ○ ○
In critically ill medical patients the panel suggests not using GCS for prophylaxis of VTE (conditional recommendation, very low quality evi-
dence)

In critically ill medical patients at high risk of bleeding and in whom pharmacological prophylaxis is not feasible and in settings where IPC is
not available the panel suggests using GCS for prophylaxis of VTE (conditional recommendation, very low quality evidence)
Recommendation
Remarks:
1. Consider monitoring for skin lesions and ischemia
2. Physician must ensure proper fitting
3. Ensure appropriate use of GCS (thigh length vs. knee length)

The panel judged the harms of GCS for prophylaxis of VTE to probably outweigh the benefits in critically ill medical patients. The certainty of
Justification
the evidence was considered to be low. The panel judged the intervention to be low-cost, probably cost effective, feasible and acceptable.

Subgroup considerations None

Implementation considera-
 The hospital should acquire different sizes of GCS of high quality
tions

1. Consider introducing the risk stratification form for critically ill medical patients
Monitoring and evaluation 2. Consider monitoring percentage of patients getting the risk stratification form completed
3. Consider monitoring percentage of critically ill patients using GCS

1. Benefits and harms in ICU populations

Research possibilities
2. Cost effectiveness
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
85

Evidence Profile: GCS compared to no GCS for critically ill patients

Bibliography (systematic reviews): Arabi, Y. M., Khedr, M., Dara, S. I., Dhar, G. S., Bhat, S. A., Tamim, H. M., & Afesh, L. Y. (2013). Use of intermittent pneumatic compres-
sion and not graduated compression stockings is associated with lower incident VTE in critically ill patients: a multiple propensity scores adjusted analysis. Chest, 144(1),
152-159.

Quality assessment № of patients Effect

Quality Importance
№ of stud- Risk of Other considera- Relative Absolute
Study design Inconsistency Indirectness Imprecision GCS no GCS
ies bias tions (95% CI) (95% CI)

VTE
1 34
1 observational stud- not seri- not serious not serious serious none 18/180 28/389 HR 1.04 3 more per 1000 (from 29 ⨁◯◯ Critical
ies 2 ous (10.0%) (7.2%) (0.59 to fewer to 69 more) ◯
2.04) VERY
LOW

Hospital mortality
1 34
1 observational stud- not seri- not serious not serious serious none HR 0.86 1 fewer per 1000 (from 0 ⨁◯◯ Important
ies 2 ous (0.62 to fewer to 0 fewer) ◯
1.21) VERY
LOW

Skin breaks/ulcers/blisters/skin necrosis (follow up: 30 days)

5 6 7 3
1 randomised trials serious not serious serious serious none 64/1256 16/1262 RR 1.06 1 more per 1000 (from 1 ⨁◯◯ Important
(5.1%) (1.3%) (0.94 to fewer to 3 more) ◯
1.2) VERY
LOW

Lower limb ischemia/amputation (follow up: 30 days)

5 6 7 3
1 randomised trials serious not serious serious serious none 7/1256 2/1262 RR 3.52 4 more per 1000 (from 0 ⨁◯◯ Important
(0.6%) (0.2%) (0.73 to fewer to 25 more) ◯
16.9) VERY
LOW

MD – mean difference, RR – relative risk

1. Arabi et al. 2013
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
86

2. The observational study used the Multiple Propensity Scores Adjusted Analysis
3. Serious imprecision. 95% CI includes both estimates suggesting important benefit and estimates suggesting important harm
4. Serious imprecision related to a total number of events less than 300
5. CLOTS trial
6. Serious risk of bias. Studies that carried large weight for the overall effect estimate classified as high risk of bias due to lack of blinding to treatment allocation and
assessment of outcomes was based on case note review
7. Serious indirectness. Patients included in the CLOTS trial (only stroke patients) differ from the PICO for this recommendation

References:

1. Heit J A, Silverstein M D, Mohr D N, Petterson T M, O’Fallon W M, Melton L J I II. Risk factors for deep vein thrombosis and pulmonary em-
bolism: a population-based case-control study. Arch Intern Med . 2000; 160 (6): 809 - 815.
2. Decousus H, Tapson VF, Bergmann JF, et al; IMPROVE Investigators. Factors at admission associated with bleeding risk in medical patients: find-
ings from the IMPROVE investigators. Chest. 2011; 139 (1): 69 - 79.
3. Anderson FA Jr, Wheeler HB, Goldberg RJ, et al. A population-based perspective of the hospital incidence and case-fatality rates of deep vein
thrombosis and pulmonary embolism: the Worcester DVT Study. Arch Intern Med 1991;151:933-938. 4.
4. Goldhaber SZ, Dunn K, MacDougall RC. New onset of venous thromboembolism among hospitalized patients at Brigham and Women’s Hospital is
caused more often by prophylaxis failure than by withholding treatment. Chest 2000;118:1680-1684.
5. Goldhaber SZ, Tapson VF. A prospective registry of 5,451 patients with ultrasound-confirmed deep vein thrombosis. Am J Cardiol 2004;93:259-262.
6. Ishi, S. V., Lakshmi, M., Kakde, S. T., Sabnis, K. C., Jagannati, M., Girish, T. S., . . . Cherian, A. M. (2013). Randomised controlled trial for efficacy of un-
fractionated heparin (UFH) versus low molecular weight heparin (LMWH) in thrombo-prophylaxis. Journal of the Association of Physicians of India,
61(12), 882-886.
7. Hirsch DR, Ingenito EP, Goldhaber SZ: Prevalence of deep venous thrombosis among patients in medical intensive care. JAMA 1995;274:335–337.
8. Moser KM, LeMoine JR, Nachtwey FJ, et al: Deep venous thrombosis and pulmonary embolism. Frequency in a respiratory intensive care unit. JAMA
1981; 246:1422–1424.
9. Alhazzani, W., Lim, W., Jaeschke, R. Z., Murad, M. H., Cade, J., & Cook, D. J. (2013). Heparin Thromboprophylaxis in Medical-Surgical Critically Ill Pa-
tients: A Systematic Review and Meta-Analysis of Randomized Trials*. Critical care medicine, 41(9), 2088-2098.
10. Arnold DM, Donahoe L, Clarke FJ, et al: Bleeding during critical illness: A prospective cohort study using a new measurement tool. Clin Invest Med
2007; 30:E93–102.
11. Goldhaber SZ: Venous thromboembolism in the intensive care unit: The last frontier for prophylaxis. Chest 1998; 113:5–7
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
87

12. Cook D, Meade M, Guyatt G, et al; PROTECT Investigators for the Canadian Critical Care Trials Group and the Australian and New Zealand Intensive
Care Society Clinical Trials Group. Dalteparin versus unfractionated heparin in critically ill patients . N Engl J Med . 2011 ; 364 ( 14 ): 1305 - 1314 .
13. Qaseem A , Chou R , Humphrey LL , Starkey M , Shekelle P ;Clinical Guidelines Committee of the American College of Physicians . Venous thrombo-
embolism prophylaxis in hospitalized patients: a clinical practice guideline from the American College of Physicians . Ann Intern Med . 2011; 155( 9):
625- 632.
14. Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ ; American College of Chest Physicians. Executive summary: antithrombotic ther-
apy and prevention of thrombosis, 9th ed:
American College of Chest Physicians evidence-based clinical practice guidelines. Chest . 2012 141(2)(suppl):7S-47S.
15. Arabi, Y. M., Khedr, M., Dara, S. I., Dhar, G. S., Bhat, S. A., Tamim, H. M., & Afesh, L. Y. (2013). Use of intermittent pneumatic compression and not
graduated compression stockings is associated with lower incident VTE in critically ill patients: a multiple propensity scores adjusted analysis. Chest,
144(1), 152-159.
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
88

Guideline Question 9: Should IPC versus no IPC be used for critically ill patients?

Problem: Critically ill patients Background and Objective: Many trials have recommended the use of pharmacologic prophylaxis for critically ill
Option: IPC patients.29,30 However limited data exists on the use of mechanical thromboprophylaxis including IPC and GCS.4,31,32
Comparison: No IPC
Setting:
Perspective: The KSA MoH

Additional con-
Criteria Judgements Research evidence
siderations

○ No No evidence specific to KSA identified

○ Probably no
Is there a problem priori- ○ Uncertain
Problem
ty?
● Probably yes
○ Yes
○ Varies

The relative importance or values of the main outcomes of interest:

○ Important uncer-
tainty or variability
Is there important uncer- Relative im- Certainty of the evidence
Benefits & Outcome
harms of
tainty about how much ○ Possibly im- portance (GRADE)
people value the main
the options portant uncertainty
outcomes? VTE Critical Very Low
or variability

● Probably no im- Hospital mortali-

Important Very Low
ty
portant uncertainty
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
89

Additional con-
Criteria Judgements Research evidence
siderations

of variability

○ No important
uncertainty of vari-
ability Summary of findings:

○ No known unde-
Relative ef-
sirable Without Difference (95%
Outcome With IPC fect (RR)
IPC CI)
(95% CI)

○ No included 28/389 11/229

39 fewer per 1000 HR 0.45
studies VTE (from 3 fewer to (0.22 to
(7.2%) (4.8%)
56 fewer) 0.95)
● Very low
What is the overall cer- 1 fewer per 1000 HR 0.92
tainty of this evidence? ○ Low Hospital
mortality
Not esti-
mated
Not esti-
mated
(from 0 fewer to 0 (0.68 to
fewer) 1.24)
○ Moderate
○ High

○ No
○ Probably no
Are the desirable antici- ○ Uncertain
pated effects large?
● Probably yes
○ Yes
○ Varies
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
90

Additional con-
Criteria Judgements Research evidence
siderations

○ No
○ Probably no
Are the undesirable antic- ● Uncertain
ipated effects small?
○ Probably yes
○ Yes
○ Varies

○ No
○ Probably no
Are the desirable effects ●Uncertain
large relative to undesira-
ble effects? ○ Probably yes
○ Yes
○ Varies

○ No No evidence specific to KSA identified

● Probably no
Resource Are the resources re-
use quired small? ○ Uncertain
○ Probably yes
○ Yes
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
91

Additional con-
Criteria Judgements Research evidence
siderations

○ Varies

Appropriate prophylaxis provides better value in terms of costs and health gains
○ No than routine screening for DVT. Resources should be targeted at optimizing throm-
boprophylaxis.
○ Probably no
Is the incremental cost ● Uncertain
small relative to the net
benefits? ○ Probably yes
○ Yes
○ Varies

○ Increased No evidence specific to KSA identified Cost and availa-

bility
● Probably in-
creased

Equity
What would be the impact ○ Uncertain
on health inequities?
○ Probably reduced
○ Reduced
○ Varies

Acceptability
Is the option acceptable ○ No No evidence specific to KSA identified
to key stakeholders?
○ Probably no
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
92

Additional con-
Criteria Judgements Research evidence
siderations

○ Uncertain
● Probably yes
○ Yes
○ Varies

○ No No evidence specific to KSA identified May vary among

hospitals
○ Probably no
Is the option feasible to ○ Uncertain
Feasibility
implement?
● Probably yes
○ Yes
○ Varies
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
93

Recommendation
Should IPC versus no IPC be used for critically ill patients?
Undesirable consequences Undesirable consequences Desirable consequences Desirable consequences
The balance between desirable
Balance of con- clearly outweigh desirable probably outweigh desirable probably outweigh undesira- clearly outweigh undesirable
and undesirable consequences
sequences consequences in most set- consequences in most set- ble consequences in most consequences in most set-
is closely balanced or uncertain
tings tings settings tings

○ ○ ○ ● ○
We recommend against of- We suggest not offering this We suggest offering this op-
Type of recommendation We recommend offering this option
fering this option option tion

○ ○ ● ○
In critically ill medical patients who are bleeding or at high risk of bleeding, the panel suggests using IPC/ SCD for the prophylaxis of VTE
(conditional recommendation, very low quality evidence).
Recommendation
In critically ill medical patients at high risk of VTE receiving pharmacological prophylaxis the panel suggests adding IPC/ SCD for the prophy-
laxis of VTE (conditional recommendation, very low quality evidence).

The panel judged the benefits of IPC/SCD for the prophylaxis of VTE to probably outweigh the harms in critically ill medical patients who are
Justification bleeding, at high risk of bleeding or at high risk of VTE receiving pharmacological prophylaxis. The certainty of the evidence was considered
to be very low. The panel judged the intervention to be low-cost, probably cost effective and probably acceptable

Subgroup considerations None

1. Consider introducing the risk stratification form for critically ill medical patients
Implementation considera-
2. Consider monitoring percentage of patients getting the risk stratification form completed
tions
3. Consider monitoring percentage of critically ill medical patients using IPC

Monitoring and evaluation None

1. Effectiveness
Research possibilities
2. Test for Combination of interventions
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
94

Evidence Profile: IPC compared to no IPC for critically ill patients

Bibliography (systematic reviews): Arabi, Y. M., Khedr, M., Dara, S. I., Dhar, G. S., Bhat, S. A., Tamim, H. M., & Afesh, L. Y. (2013). Use of intermittent pneumatic compres-
sion and not graduated compression stockings is associated with lower incident VTE in critically ill patients: a multiple propensity scores adjusted analysis. Chest, 144(1),
152-159.

Quality assessment № of patients Effect

Quality Importance
№ of stud- Risk of Other considera- Relative Absolute
Study design Inconsistency Indirectness Imprecision IPC no IPC
ies bias tions (95% CI) (95% CI)

VTE
3
1 observational not seri- not serious not serious serious none 11/229 28/389 HR 0.45 39 fewer per 1000 (from ⨁◯◯◯ Critical
studies ous (4.8%) (7.2%) (0.22 to 0.95) 3 fewer to 56 fewer) VERY LOW

Hospital mortality
123
1 observational not seri- not serious not serious serious none HR 0.92 1 fewer per 1000 (from 0 ⨁◯◯◯ Important
studies ous (0.68 to 1.24) fewer to 0 fewer) VERY LOW

Skin breaks/ulcers/blisters/skin necrosis - not reported

- - - - - - - - see com- not estimable see comment -

ment

MD – mean difference, RR – relative risk

1. Arabi 2013
2. Serious imprecision. 95% CI includes both estimates suggesting important benefit and estimates suggesting important harm
3. Serious imprecision related to a total number of events less than 300

References:

1. Heit J A, Silverstein M D, Mohr D N, Petterson T M, O’Fallon W M, Melton L J I II. Risk factors for deep vein thrombosis and pulmonary em-
bolism: a population-based case-control study . Arch Intern Med . 2000 ; 160 ( 6 ): 809 - 815 .
2. Decousus H , Tapson VF , Bergmann JF , et al ; IMPROVE Investigators. F actors at admission associated with bleeding risk in medical patients:
findings from the IMPROVE investigators . Chest . 2011 ; 139 ( 1 ): 69 - 79 .
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
95

3. Anderson FA Jr, Wheeler HB, Goldberg RJ, et al. A population-based perspective of the hospital incidence and case-fatality rates of deep vein
thrombosis and pulmonary embolism: the Worcester DVT Study. Arch Intern Med 1991;151:933-938. 4.
4. Goldhaber SZ, Dunn K, MacDougall RC. New onset of venous thromboembolism among hospitalized patients at Brigham and Women’s Hospital is
caused more often by prophylaxis failure than by withholding treatment. Chest 2000;118:1680-1684.
5. Goldhaber SZ, Tapson VF. A prospective registry of 5,451 patients with ultrasound-confirmed deep vein thrombosis. Am J Cardiol 2004;93:259-262.
6. Ishi, S. V., Lakshmi, M., Kakde, S. T., Sabnis, K. C., Jagannati, M., Girish, T. S., . . . Cherian, A. M. (2013). Randomised controlled trial for efficacy of un-
fractionated heparin (UFH) versus low molecular weight heparin (LMWH) in thrombo-prophylaxis. Journal of the Association of Physicians of India,
61(12), 882-886.
7. Hirsch DR, Ingenito EP, Goldhaber SZ: Prevalence of deep venous thrombosis among patients in medical intensive care. JAMA 1995;274:335–337.
8. Moser KM, LeMoine JR, Nachtwey FJ, et al: Deep venous thrombosis and pulmonary embolism. Frequency in a respiratory intensive care unit. JAMA
1981; 246:1422–1424.
9. Alhazzani, W., Lim, W., Jaeschke, R. Z., Murad, M. H., Cade, J., & Cook, D. J. (2013). Heparin Thromboprophylaxis in Medical-Surgical Critically Ill Pa-
tients: A Systematic Review and Meta-Analysis of Randomized Trials*. Critical care medicine, 41(9), 2088-2098.
10. Arnold DM, Donahoe L, Clarke FJ, et al: Bleeding during critical illness: A prospective cohort study using a new measurement tool. Clin Invest Med
2007; 30:E93–102.
11. Goldhaber SZ: Venous thromboembolism in the intensive care unit: The last frontier for prophylaxis. Chest 1998; 113:5–7
12. Cook D, Meade M, Guyatt G, et al; PROTECT Investigators for the Canadian Critical Care Trials Group and the Australian and New Zealand Intensive
Care Society Clinical Trials Group. Dalteparin versus unfractionated heparin in critically ill patients . N Engl J Med . 2011 ; 364 ( 14 ): 1305 - 1314 .
13. Qaseem A , Chou R , Humphrey LL , Starkey M , Shekelle P ;Clinical Guidelines Committee of the American College of Physicians . Venous thrombo-
embolism prophylaxis in hospitalized
patients: a clinical practice guideline from the American College of Physicians . Ann Intern Med . 2011; 155( 9): 625- 632.
14. Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ ; American College of Chest Physicians. Executive summary: antithrombotic ther-
apy and prevention of thrombosis, 9th ed:
American College of Chest Physicians evidence-based clinical practice guidelines. Chest . 2012 141(2)(suppl):7S-47S.
15. Arabi, Y. M., Khedr, M., Dara, S. I., Dhar, G. S., Bhat, S. A., Tamim, H. M., & Afesh, L. Y. (2013). Use of intermittent pneumatic compression and not
graduated compression stockings is associated with lower incident VTE in critically ill patients: a multiple propensity scores adjusted analysis. Chest,
144(1), 152-159.
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
96

Guideline Question 10: Should thromboprophylaxis be used for prophylaxis of DVT in chronically ill medical patients?

Problem: Chronically ill medical patients Background and Objective: The chronically population who is immobile includes homebound
Option: Prophylactic thromboprophylaxis patients, and residents of nursing homes and post-acute care facilities. One study of nursing
Comparison: No prophylaxis home residents found a symptomatic VTE incidence of 0.91 per 100 person-years.
Setting:
Perspective: The KSA MoH

Additional
Criteria Research evidence
Judgements considerations

No evidence specific to KSA identified

○ No
○ Probably no
Problem
Is there a prob-
lem priority?
○ Uncertain
● Probably yes
○ Yes
○ Varies
The relative importance or values of the main outcomes of interest:
○ Important
uncertainty or
variability Outcome Relative importance Certainty of the evidence (GRADE)
Is there im-
Benefits &
portant uncertain-
ty about how
○
Possibly DVT Critical Very low (expert based)
harms of important un-
much people val- PE Critical Very low (expert based)
the options certainty or
ue the main out-
variability
comes? Major bleeding Critical Very low (expert based)
●
Probably no
important un- Minor Bleeding Important Very low (expert based)
certainty of
variability
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
97

Additional
Criteria Research evidence
Judgements considerations

○ No im- Thrombocytopenia Important Very low (expert based)

portant uncer-
Mortality Important Very low (expert based)
tainty of varia-
bility
○ No known Summary of findings:
undesirable

● No included Relative
effect
studies Without thrombo- With thrombo- Difference
Outcome (OR)
prophylaxis prophylaxis (95% CI)
What is the over-
all certainty of
○ Very low (95%
CI)
this evidence? ○ Low
○ Moderate
○ High
DVT
○ No
○ Probably no
Are the desirable
anticipated ef- ● Uncertain
fects large? PE
○ Probably yes
Major bleeding
○ Yes
Minor Bleeding
○ Varies
Thrombocytopenia
○ No Mortality
Are the undesira-
ble anticipated ○ Probably no
effects small?
● Uncertain
○ Probably yes
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
98

Additional
Criteria Research evidence
Judgements considerations

○ Yes
○ Varies
○ No
Are the desirable ○ Probably no
effects large rela-
tive to undesira-
● Uncertain
ble effects? ○ Probably yes
○ Yes
○ Varies
No evidence specific to KSA identified
○ No
○ Probably no
Are the resources ● Uncertain
required small?
○ Probably yes
○ Yes
Resource
○ Varies
use
No evidence specific to KSA identified
○ No
Is the incremental ○ Probably no
cost small relative
to the net bene-
● Uncertain
fits? ○ Probably yes
○ Yes
○ Varies
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
99

Additional
Criteria Research evidence
Judgements considerations

No evidence specific to KSA identified

○ Increased
○ Probably
increased
What would be
Equity the impact on ● Uncertain
health inequities?
○ Probably
reduced
○ Reduced
○ Varies
No evidence specific to KSA identified
○ No
● Probably no
Is the option ac-
Acceptability ceptable to key ○ Uncertain
stakeholders?
○ Probably yes
○ Yes
○ Varies
No evidence specific to KSA identified
○ No
● Probably no
Is the option fea-
Feasibility sible to imple- ○ Uncertain
ment?
○ Probably yes
○ Yes
○ Varies
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
100

Recommendation
Should thromboprophylaxis versus no thromboprophylaxis be used for Prophylaxis of DVT in chronically ill medical
patients?
Undesirable consequences Undesirable consequences The balance between desir- Desirable consequences
Desirable consequences clearly out-
Balance of conse- clearly outweigh desirable probably outweigh desira- able and undesirable conse- probably outweigh unde-
weigh undesirable consequences in
quences consequences in most ble consequences in most quences is closely balanced sirable consequences in
most settings
settings settings or uncertain most settings

○ ● ○ ○ ○
We recommend against We suggest not offering We suggest offering this
Type of recommendation We recommend offering this option
offering this option this option option

○ ● ○ ○
In chronically ill medical patients the panel suggests not using versus using prophylaxis for VTE (conditional recommendation, very low
Recommendation
quality evidence)

The panel judged the harms of prophylaxis to probably outweigh its benefits in chronically ill medical patients. The certainty of the evidence
Justification was considered to be very low. The panel members were uncertain regarding the cost and cost effectiveness of the intervention and judged
it to probably be neither feasible nor acceptable.

Subgroup considerations None

Implementation considerations None

Monitoring and evaluation None

Research possibilities Trials testing the efficacy and safety of thromboprophylaxis in chronically ill patients
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
101

Guideline Question 11: Should frequent ambulation be used for long-distance travelers at increased risk of VTE?

Problem: Long-distance travelers at increased risk of Background and Objective: Long distance travelling is a risk factor for venous thromboembolism
VTE especially among individuals who have any of the known risk factors as previous VTE, recent
Option: frequent ambulation surgery or trauma, active malignancy, pregnancy, estrogen use, advanced age, limited mobility,
Comparison: No frequent ambulation severe obesity or thromboembolic disorder.32-37 Some studies suggested that the risk is highest
for flights more than 8 hours long.20,21,35,38-40 Protective measures suggested include frequent
Setting: Outpatient
ambulation, sitting in aisle seat, hydration and light compression stocking. 33
Perspective: The KSA MoH

Additional con-
Criteria Research evidence
Judgements siderations

No evidence specific to KSA identified

○ No
○ Probably no
Problem Is there a problem priority? ○ Uncertain
● Probably yes
○ Yes
○ Varies
The relative importance or values of the main outcomes of interest:
○ Important uncer-
tainty or variability
Relative im- Certainty of the evidence
Benefits &
Is there important uncer- ○ Possibly im- Outcome
portance (GRADE)
tainty about how much portant uncertainty
harms of
people value the main out- or variability Symptomatic
the options Critical Very low
comes? DVT
● Probably no im-
portant uncertainty PE Critical Very low
of variability
○ No important
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
102

Additional con-
Criteria Research evidence
Judgements siderations

uncertainty of varia- Summary of findings:

bility
○ No known unde- The Multiple Environmental and Genetic Assessment of risk factors for venous
thrombosis study found an adjusted odds ratio for the association between exer-
sirable cising during flight and the risk of thrombosis of 1.2 (95% CI 0.6-2.6).

● No included stud-
ies
What is the overall certain- ○ Very low
ty of this evidence?
○ Low
○ Moderate
○ High
○ No
○ Probably no
Are the desirable anticipat-
ed effects large?
● Uncertain
○ Probably yes
○ Yes
○ Varies
○ No
○ Probably no
Are the undesirable antici-
pated effects small?
● Uncertain
○ Probably yes
○ Yes
○ Varies
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
103

Additional con-
Criteria Research evidence
Judgements siderations

○ No
○ Probably no
Are the desirable effects
large relative to undesira- ● Uncertain
ble effects?
○ Probably yes
○ Yes
○ Varies
No evidence specific to KSA identified
○ No
○ Probably no
Are the resources required
small?
○ Uncertain
○ Probably yes
● Yes
Resource ○ Varies
use
No evidence specific to KSA identified
○ No
○ Probably no
Is the incremental cost
small relative to the net ○ Uncertain
benefits?
● Probably yes
○ Yes
○ Varies
No evidence specific to KSA identified
Equity
What would be the impact ○ Increased
on health inequities?
○ Probably in-
creased
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
104

Additional con-
Criteria Research evidence
Judgements siderations

● Uncertain
○ Probably reduced
○ Reduced
○ Varies
No evidence specific to KSA identified
○ No
○ Probably no
Acceptability
Is the option acceptable to
key stakeholders?
○ Uncertain
● Probably yes
○ Yes
○ Varies
No evidence specific to KSA identified
○ No
○ Probably no
Feasibility
Is the option feasible to
implement?
○ Uncertain
● Probably yes
○ Yes
○ Varies
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
105

Recommendation
Should frequent ambulation versus no frequent ambulation be used for VTE in long distance travelers?
Undesirable consequences Undesirable consequences Desirable consequences Desirable consequences
The balance between desirable
Balance of con- clearly outweigh desirable probably outweigh desirable probably outweigh undesira- clearly outweigh undesirable
and undesirable consequences
sequences consequences in most set- consequences in most set- ble consequences in most consequences in most set-
is closely balanced or uncertain
tings tings settings tings

○ ○ ○ ● ○
We recommend against of- We suggest not offering this We recommend offering this
Type of recommendation We suggest offering this option
fering this option option option

○ ○ ● ○
In long distance high-risk travelers (>8hrs) the panel suggests frequent ambulation for the prophylaxis of VTE (conditional recommendation,
Recommendation
very low quality evidence)

The panel judged the benefits of frequent ambulation for the prophylaxis of VTE to probably outweigh the harms in long distance travelers
Justification (>8hrs). The certainty of the evidence was considered to be very low. The panel judged the intervention to be low-cost, probably cost effec-
tive, feasible and acceptable.

Subgroup considerations None

Implementation considera-
None
tions

Monitoring and evaluation None

Research possibilities None

References:

1. Kesteven P , Robinson B . Incidence of symptomatic thrombosis in a stable population of 650,000: travel and other risk factors . Aviat Space Environ
Med . 2002 ; 73 ( 6 ): 593 - 596 .
2. Cannegieter SC , Doggen CJ , van Houwelingen HC , Rosendaal FR . Travel-related venous thrombosis: results from a large population-based case con-
trol study (MEGAstudy) . PLoS Med . 2006 ; 3 ( 8 ): e307 .
3. Schwarz T , Siegert G , Oettler W , et al . Venous thrombosis after long-haul flights. Arch Intern Med . 2003 ; 163 ( 22 ):2759 - 2764 .
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
106

4. Arfvidsson B , Eklof B , Kistner RL , Masuda EM , Sato DT .Risk factors for venous thromboembolism following prolonged air travel. Coach class throm-
bosis. Hematol Oncol Clin North Am . 2000 ; 14 ( 2 ): 391 - 400; ix .
5. Martinelli I , Taioli E , Battaglioli T , et al . Risk of venous thromboembolism after air travel: interaction with thrombophilia and oral contraceptives .
Arch Intern Med . 2003 ; 163 ( 22 ): 2771 - 2774 .
6. Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ ; American College of Chest Physicians. Executive summary: antithrombotic therapy
and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest . 2012 141(2)(suppl):7S-
47S.
7. Lapostolle F , Surget V , Borron SW , et al . Severe pulmonary embolism associated with air travel . N Engl J Med . 2001 ; 345 ( 11 ): 779 - 783 .
8. Hughes RJ , Hopkins RJ , Hill S , et al . Frequency of venous thromboembolism in low to moderate risk long distance air travellers: the New Zealand Air
Traveller’s Thrombosis
9. Hughes RJ1, Hopkins RJ, Hill S, Weatherall M, Van de Water N, Nowitz M, Milne D, Ayling J, Wilsher M, Beasley R. Frequency of venous thromboembo-
lism in low to moderate risk long distance air travellers: the New Zealand Air Traveller's Thrombosis (NZATT) study. Lancet. 2003 Dec
20;362(9401):2039-44.
10. Philbrick JT , Shumate R , Siadaty MS , Becker DM . Air travel and venous thromboembolism: a systematic review . J Gen Intern Med . 2007 ; 22 ( 1 ):
107 - 114 .
11. Schwarz T , Siegert G , Oettler W , et al . Venous thrombosis after long-haul flights . Arch Intern Med . 2003 ; 163 ( 22 ): 2759 - 2764 .
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
107

Guideline Question 12: Should calf muscle exercise versus no calf muscle exercise be used for VTE in long distance travelers?

Problem: Long distance travelers
Option: Calf muscle exercise
Comparison: No calf exercise
Setting: Outpatient
Perspective: The KSA MoH
Background and Objective: Long distance travelling is a risk factor for venous thromboembolism
especially among individuals who have any of the known risk factors as previous VTE, recent
surgery or trauma, active malignancy, pregnancy, estrogen use, advanced age, limited mobility,
severe obesity or thromboembolic disorder.32-37 Some studies suggested that the risk is highest
for flights more than 8 hours long.20,21,35,38-40 Protective measures suggested include frequent
ambulation, sitting in aisle seat, hydration and light compression stocking.32

Additional con-
Criteria Judgements Research evidence
siderations

No evidence specific to KSA identified

○ No
○ Probably no
Problem Is there a problem priority?
○ Uncertain
● Probably yes
○ Yes
○ Varies
The relative importance or values of the main outcomes of interest:
○ Important uncer-
tainty or variability Relative im- Certainty of the evidence
Outcome
portance (GRADE)
○ Possibly im-
portant uncertainty Symptomatic Very low
Is there important uncer- Critical
Benefits & or variability DVT
tainty about how much
harms of
the options
people value the main out- ● Probably no im- PE Critical Very low
comes? portant uncertainty
of variability Summary of findings:
○ No important The Multiple Environmental and Genetic Assessment of risk factors for venous
thrombosis study found an adjusted odds ratio for the association between exer-
uncertainty of varia-
cising during flight and the risk of thrombosis of 1.2 (95% CI 0.6-2.6).
bility
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
108

Additional con-
Criteria Judgements Research evidence
siderations

○ No known unde-
sirable

● No included stud-
ies

What is the overall certain-

○ Very low
ty of this evidence? ○ Low
○ Moderate
○ High
○ No
○ Probably no
Are the desirable anticipat- ● Uncertain
ed effects large?
○ Probably yes
○ Yes
○ Varies
○ No
○ Probably no
Are the undesirable antici- ● Uncertain
pated effects small?
○ Probably yes
○ Yes
○ Varies
Are the desirable effects
large relative to undesira- ○ No
ble effects?
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
109

Additional con-
Criteria Judgements Research evidence
siderations

○ Probably no
● Uncertain
○ Probably yes
○ Yes
○ Varies
No evidence specific to KSA identified
○ No
○ Probably no
Are the resources required ○ Uncertain
small?
○ Probably yes
● Yes
Resource
○ Varies
use
No evidence specific to KSA identified
○ No
○ Probably no
Is the incremental cost
small relative to the net
○ Uncertain
benefits? ● Probably yes
○ Yes
○ Varies
No evidence specific to KSA identified
○ Increased
Equity
What would be the impact ○ Probably in-
on health inequities? creased
● Uncertain
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
110

Additional con-
Criteria Judgements Research evidence
siderations

○ Probably reduced
○ Reduced
○ Varies
No evidence specific to KSA identified
○ No
○ Probably no
Acceptability
Is the option acceptable to ○ Uncertain
key stakeholders?
● Probably yes
○ Yes
○ Varies
No evidence specific to KSA identified
○ No
○ Probably no
Feasibility
Is the option feasible to ○ Uncertain
implement?
● Probably yes
○ Yes
○ Varies
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
111

Recommendation
Should calf muscle exercise versus no calf muscle exercise be used for VTE in long distance travelers?
Undesirable consequences Undesirable consequences Desirable consequences Desirable consequences
The balance between desirable
Balance of con- clearly outweigh desirable probably outweigh desirable probably outweigh undesira- clearly outweigh undesirable
and undesirable consequences
sequences consequences in most set- consequences in most set- ble consequences in most consequences in most set-
is closely balanced or uncertain
tings tings settings tings

○ ○ ○ ● ○
We recommend against of- We suggest not offering this We recommend offering this
Type of recommendation We suggest offering this option
fering this option option option

○ ○ ● ○
In long distance high-risk travelers (>8hrs) the panel suggests calf muscle exercise for the prophylaxis of VTE (conditional recommendation,
Recommendation
very low quality evidence).

The panel judged the benefits of calf muscle exercise for prophylaxis of VTE to probably outweigh the harms in long distance travelers. The
Justification
certainty of the evidence was considered to be very low. The panel judged the intervention to be feasible and acceptable.

Subgroup considerations None

Implementation considera-
None
tions

Monitoring and evaluation None

Research possibilities None

References:

1. Kesteven P , Robinson B . Incidence of symptomatic thrombosis in a stable population of 650,000: travel and other risk factors . Aviat Space Environ
Med . 2002 ; 73 ( 6 ): 593 - 596 .
2. Cannegieter SC , Doggen CJ , van Houwelingen HC , Rosendaal FR . Travel-related venous thrombosis: results from a large population-based case con-
trol study (MEGAstudy) . PLoS Med . 2006 ; 3 ( 8 ): e307 .
3. Schwarz T , Siegert G , Oettler W , et al . Venous thrombosis after long-haul flights . Arch Intern Med . 2003 ; 163 ( 22 ):2759 - 2764 .
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
112

4. Arfvidsson B , Eklof B , Kistner RL , Masuda EM , Sato DT .Risk factors for venous thromboembolism following prolonged air travel. Coach class throm-
bosis . Hematol Oncol Clin North Am . 2000 ; 14 ( 2 ): 391 - 400; ix .
5. Martinelli I , Taioli E , Battaglioli T , et al . Risk of venous thromboembolism after air travel: interaction with thrombophilia and oral contraceptives .
Arch Intern Med . 2003 ; 163 ( 22 ): 2771 - 2774 .
6. Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ ; American College of Chest Physicians. Executive summary: antithrombotic therapy
and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest . 2012 141(2)(suppl):7S-
47S.
7. Lapostolle F , Surget V , Borron SW , et al . Severe pulmonary embolism associated with air travel . N Engl J Med . 2001 ; 345 ( 11 ): 779 - 783 .
8. Hughes RJ , Hopkins RJ , Hill S , et al . Frequency of venous thromboembolism in low to moderate risk long distance air travellers: the New Zealand Air
Traveller’s Thrombosis
9. Hughes RJ, Hopkins RJ, Hill S, Weatherall M, Van de Water N, Nowitz M, Milne D, Ayling J, Wilsher M, Beasley R. Frequency of venous thromboembo-
lism in low to moderate risk long distance air travellers: the New Zealand Air Traveller's Thrombosis (NZATT) study. Lancet. 2003 Dec
20;362(9401):2039-44.
10. Philbrick JT , Shumate R , Siadaty MS , Becker DM . Air travel and venous thromboembolism: a systematic review . J Gen Intern Med . 2007 ; 22 ( 1 ):
107 - 114 .
11. Schwarz T , Siegert G , Oettler W , et al . Venous thrombosis after long-haul flights . Arch Intern Med . 2003 ; 163 ( 22 ): 2759 - 2764 .
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
113

Guideline Question 13: Should sitting in an aisle seat versus no sitting in an aisle seat be used for VTE in long distance travelers?

Problem: Long distance travelers
Option: Sitting in aisle seat
Comparison: No sitting in aisle seat
Setting: Outpatient
Perspective: The KSA MoH
Background and Objective: Long distance travelling is a risk factor for venous thromboembolism
especially among individuals who have any of the known risk factors as previous VTE, recent
surgery or trauma, active malignancy, pregnancy, estrogen use, advanced age, limited mobility,
severe obesity or thromboembolic disorder.32-37 Some studies suggested that the risk is highest
for flights more than 8 hours long.20,21,35,38-40 Protective measures suggested include frequent
ambulation, sitting in aisle seat, hydration and light compression stocking.32

Additional con-
Criteria Research evidence
Judgements siderations

No evidence specific to KSA identified

○ No
○ Probably no
Problem
Is there a problem priori-
ty?
○ Uncertain
● Probably yes
○ Yes
○ Varies
The relative importance or values of the main outcomes of interest:
○ Important uncer-
tainty or variability
Relative im- Certainty of the evidence
Is there important uncer-
○ Possibly im- Outcome
portance (GRADE)
Benefits & portant uncertainty
tainty about how much
harms of or variability Symptomatic Very low
people value the main out- Critical
the options DVT
comes? ● Probably no im-
portant uncertainty PE Critical Very low
of variability
○ No important
uncertainty of vari-
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
114

Additional con-
Criteria Research evidence
Judgements siderations

ability Summary of findings:

○ No known unde-
sirable The Multiple Environmental and Genetic Assessment of risk factors for
venous thrombosis case–control study found that window seating com-
● No included stud- pared to aisle seating was associated with thrombosis (OR= 2.2; 95% CI
ies 1.1-4.4).
What is the overall certain- ○ Very low
ty of this evidence?
○ Low
○ Moderate
○ High
○ No
○ Probably no
Are the desirable antici-
pated effects large?
● Uncertain
○ Probably yes
○ Yes
○ Varies
○ No
○ Probably no
Are the undesirable antici-
pated effects small?
● Uncertain
○ Probably yes
○ Yes
○ Varies
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
115

Additional con-
Criteria Research evidence
Judgements siderations

○ No
○ Probably no
Are the desirable effects ● Uncertain
large relative to undesira-
ble effects? ○ Probably yes
○ Yes
○ Varies
No evidence specific to KSA identified
○ No
○ Probably no
Are the resources required
small?
○ Uncertain
○ Probably yes
● Yes
Resource
○ Varies
use
No evidence specific to KSA identified
○ No
○ Probably no
Is the incremental cost
small relative to the net
○ Uncertain
benefits? ● Probably yes
○ Yes
○ Varies
No evidence specific to KSA identified

What would be the impact ○ Increased

Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
116

Additional con-
Criteria Research evidence
Judgements siderations

Equity on health inequities?

○ Probably in-
creased
● Uncertain
○ Probably reduced
○ Reduced
○ Varies
No evidence specific to KSA identified
○ No
○ Probably no
Acceptability
Is the option acceptable to
key stakeholders?
○ Uncertain
● Probably yes
○ Yes
○ Varies
No evidence specific to KSA identified
○ No
○ Probably no
Feasibility
Is the option feasible to
implement?
○ Uncertain
● Probably yes
○ Yes
○ Varies
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
117

Recommendation
Should sitting in an aisle seat versus no sitting in an aisle seat be used for VTE in long distance travelers?
Undesirable conse-
Undesirable conse- The balance between de- Desirable consequences Desirable consequences
quences clearly out-
Balance of con- quences probably out- sirable and undesirable probably outweigh un- clearly outweigh unde-
weigh desirable conse-
sequences weigh desirable conse- consequences is closely desirable consequences sirable consequences in
quences in most set-
quences in most settings balanced or uncertain in most settings most settings
tings

○ ○ ○ ● ○
We recommend against We suggest not offering We recommend offering
Type of recommendation We suggest offering this option
offering this option this option this option

○ ○ ● ○
In long distance high-risk travelers (>8hrs) the panel suggests sitting in an aisle seat for the prophylaxis of VTE (conditional recom-
Recommendation
mendation, very low quality evidence)

The panel judged the benefits of sitting in the aisle seat for the prophylaxis of VTE to probably outweigh the harms in long distance
Justification travelers. The certainty of the evidence was considered to be very low. The panel judged the intervention to be feasible and accepta-
ble.

Subgroup considerations None

Implementation considera-
None
tions

Monitoring and evaluation None

Research possibilities None

References:

1. Kesteven P , Robinson B . Incidence of symptomatic thrombosis in a stable population of 650,000: travel and other risk factors . Aviat Space Environ
Med . 2002 ; 73 ( 6 ): 593 - 596 .
2. Cannegieter SC , Doggen CJ , van Houwelingen HC , Rosendaal FR . Travel-related venous thrombosis: results from a large population-based case con-
trol study (MEGAstudy) . PLoS Med . 2006 ; 3 ( 8 ): e307 .
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
118

3. Schwarz T , Siegert G , Oettler W , et al . Venous thrombosis after long-haul flights . Arch Intern Med . 2003 ; 163 ( 22 ):2759 - 2764 .
4. Arfvidsson B , Eklof B , Kistner RL , Masuda EM , Sato DT .Risk factors for venous thromboembolism following prolonged air travel. Coach class throm-
bosis . Hematol Oncol Clin North Am . 2000 ; 14 ( 2 ): 391 - 400; ix .
5. Martinelli I , Taioli E , Battaglioli T , et al . Risk of venous thromboembolism after air travel: interaction with thrombophilia and oral contraceptives .
Arch Intern Med . 2003 ; 163 ( 22 ): 2771 - 2774 .
6. Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ ; American College of Chest Physicians. Executive summary: antithrombotic therapy
and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest . 2012 141(2)(suppl):7S-
47S.
7. Lapostolle F , Surget V , Borron SW , et al . Severe pulmonary embolism associated with air travel . N Engl J Med . 2001 ; 345 ( 11 ): 779 - 783 .
8. Hughes RJ , Hopkins RJ , Hill S , et al . Frequency of venous thromboembolism in low to moderate risk long distance air travellers: the New Zealand Air
Traveller’s Thrombosis
9. Hughes RJ1, Hopkins RJ, Hill S, Weatherall M, Van de Water N, Nowitz M, Milne D, Ayling J, Wilsher M, Beasley R. Frequency of venous thromboembo-
lism in low to moderate risk long distance air travellers: the New Zealand Air Traveller's Thrombosis (NZATT) study. Lancet. 2003 Dec
20;362(9401):2039-44.
10. Philbrick JT , Shumate R , Siadaty MS , Becker DM . Air travel and venous thromboembolism: a systematic review . J Gen Intern Med . 2007 ; 22 ( 1 ):
107 - 114 .
11. Schwarz T , Siegert G , Oettler W , et al . Venous thrombosis after long-haul flights . Arch Intern Med . 2003 ; 163 ( 22 ): 2759 - 2764 .
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
119

Guideline Question 14: Should anticoagulants versus no anticoagulants be used for VTE in long distance travelers?

Problem: Long distance travelers
Option: Use anticoagulants
Comparison: Not use anticoagulants
Setting: Outpatient
Perspective: The KSA MoH
Background and Objective: Long distance travelling is a risk factor for venous thromboembolism
especially among individuals who have any of the known risk factors as previous VTE, recent
surgery or trauma, active malignancy, pregnancy, estrogen use, advanced age, limited mobility,
severe obesity or thromboembolic disorder.32-37 Some studies suggested that the risk is highest
for flights more than 8 hours long.20,21,35,38-40 Protective measures suggested include frequent
ambulation, sitting in aisle seat, hydration and light compression stocking.32

Additional con-
Criteria Research evidence
Judgements siderations

No evidence specific to KSA identified

○ No
○ Probably no
Problem
Is there a problem ○ Uncertain
priority?
● Probably yes
○ Yes
○ Varies
The relative importance or values of the main outcomes of interest:
○ Important un-
certainty or vari-
ability Outcome Relative importance Certainty of the evidence (GRADE)
Is there important
Benefits &
harms of
uncertainty about how ○ Possibly im-
much people value the portant uncertain- Symptomatic DVT Critical Very low
the options
main outcomes? ty or variability
● Probably no PE Critical Very low
important uncer-
tainty of variabil-
ity
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
120

Additional con-
Criteria Research evidence
Judgements siderations

○ No important
uncertainty of Summary of findings:
variability
○ No known un- One trial compared LMWH, aspirin and no drug intervention in 300 “high-risk” air
desirable travelers (LONFLIT3 study). Participants were scanned for asymptomatic DVT, and
there were 0 events in 82 individuals receiving LMWH, 3 events in 84 receiving
● No included aspirin, and 4 events in 83 individuals in the control group. None of the reported
studies
events was a symptomatic VTE.
What is the overall
certainty of this evi-
○ Very low
dence? ○ Low
○ Moderate
○ High
○ No
○ Probably no
Are the desirable an-
ticipated effects large?
● Uncertain
○ Probably yes
○ Yes
○ Varies
○ No
Are the undesirable ○ Probably no
anticipated effects
small? ● Uncertain
○ Probably yes
○ Yes
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
121

Additional con-
Criteria Research evidence
Judgements siderations

○ Varies
○ No
○ Probably no
Are the desirable ef-
fects large relative to ● Uncertain
undesirable effects?
○ Probably yes
○ Yes
○ Varies
No evidence specific to KSA identified
○ No
● Probably no
Are the resources re-
quired small?
○ Uncertain
○ Probably yes
○ Yes
Resource ○ Varies
use
No evidence specific to KSA identified
○ No
● Probably no
Is the incremental
cost small relative to ○ Uncertain
the net benefits?
○ Probably yes
○ Yes
○ Varies
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
122

Additional con-
Criteria Research evidence
Judgements siderations

No evidence specific to KSA identified

○ Increased
○ Probably in-
creased
What would be the
Equity impact on health in- ● Uncertain
equities?
○ Probably re-
duced
○ Reduced
○ Varies
No evidence specific to KSA identified
○ No
● Probably no
Is the option accepta-
Acceptability ble to key stakehold- ○ Uncertain
ers?
○ Probably yes
○ Yes
○ Varies
No evidence specific to KSA identified
○ No
● Probably no
Feasibility
Is the option feasible
to implement?
○ Uncertain
○ Probably yes
○ Yes
○ Varies
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
123

Recommendation
Should anticoagulants versus no anticoagulants be used for VTE in long distance travelers at increased risk of VTE?
Undesirable consequences Undesirable consequences Desirable consequences Desirable consequences
The balance between desirable
Balance of con- clearly outweigh desirable probably outweigh desirable probably outweigh undesira- clearly outweigh undesirable
and undesirable consequences
sequences consequences in most set- consequences in most set- ble consequences in most consequences in most set-
is closely balanced or uncertain
tings tings settings tings

○ ○ ● ○ ○
We recommend against of- We suggest not offering this We recommend offering this
Type of recommendation We suggest offering this option
fering this option option option

○ ○ ● ○
In long distance travelers (>8hrs) at increased risk of VTE, the panel suggests using anticoagulants (conditional recommendation, very low
Recommendation
quality evidence)

The panel judged the benefits of offering pharmacological thromboprophylaxis to probably outweigh the harms in long distance travelers at
Justification increased risk of VTE. The certainty of the evidence was considered to be very low. The panel, however, judged the intervention to be neither
low-cost nor cost effective. The panel also noted the intervention may not be feasible or acceptable.

Subgroup considerations None

Implementation considera-
None
tions

Monitoring and evaluation None

Research possibilities Efficacy and safety

References:

1. Kesteven P , Robinson B . Incidence of symptomatic thrombosis in a stable population of 650,000: travel and other risk factors . Aviat Space Environ
Med . 2002 ; 73 ( 6 ): 593 - 596 .
2. Cannegieter SC , Doggen CJ , van Houwelingen HC , Rosendaal FR . Travel-related venous thrombosis: results from a large population-based case con-
trol study (MEGAstudy) . PLoS Med . 2006 ; 3 ( 8 ): e307 .
3. Schwarz T , Siegert G , Oettler W , et al . Venous thrombosis after long-haul flights . Arch Intern Med . 2003 ; 163 ( 22 ):2759 - 2764 .
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
124

4. Arfvidsson B , Eklof B , Kistner RL , Masuda EM , Sato DT .Risk factors for venous thromboembolism following prolonged air travel. Coach class throm-
bosis . Hematol Oncol Clin North Am . 2000 ; 14 ( 2 ): 391 - 400; ix .
5. Martinelli I , Taioli E , Battaglioli T , et al . Risk of venous thromboembolism after air travel: interaction with thrombophilia and oral contraceptives .
Arch Intern Med . 2003 ; 163 ( 22 ): 2771 - 2774 .
6. Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ ; American College of Chest Physicians. Executive summary: antithrombotic therapy
and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest . 2012 141(2)(suppl):7S-
47S.
7. Lapostolle F , Surget V , Borron SW , et al . Severe pulmonary embolism associated with air travel . N Engl J Med . 2001 ; 345 ( 11 ): 779 - 783 .
8. Hughes RJ , Hopkins RJ , Hill S , et al . Frequency of venous thromboembolism in low to moderate risk long distance air travellers: the New Zealand Air
Traveller’s Thrombosis
9. Hughes RJ1, Hopkins RJ, Hill S, Weatherall M, Van de Water N, Nowitz M, Milne D, Ayling J, Wilsher M, Beasley R. Frequency of venous thromboembo-
lism in low to moderate risk long distance air travellers: the New Zealand Air Traveller's Thrombosis (NZATT) study. Lancet. 2003 Dec
20;362(9401):2039-44.
10. Philbrick JT , Shumate R , Siadaty MS , Becker DM . Air travel and venous thromboembolism: a systematic review . J Gen Intern Med . 2007 ; 22 ( 1 ):
107 - 114 .
11. Schwarz T , Siegert G , Oettler W , et al . Venous thrombosis after long-haul flights. Arch Intern Med. 2003; 163 ( 22 ): 2759 - 2764 .
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
125

Guideline Question 15: Should GCS versus no GCS be used for VTE in long distance travelers?

Problem: Long distance travelers Background and Objective: Long distance travelling is a risk factor for venous thromboembolism
Option: GCS especially among individuals who have any of the known risk factors as previous VTE, recent
Comparison: No GCS surgery or trauma, active malignancy, pregnancy, estrogen use, advanced age, limited mobility,
Setting: severe obesity or thromboembolic disorder.32-37 Some studies suggested that the risk is highest
for flights more than 8 hours long.20,21,35,38-40 Protective measures suggested include frequent
Perspective: The KSA MoH
ambulation, sitting in aisle seat, hydration and light compression stocking.32

Additional con-
Criteria Research evidence
Judgements siderations

No evidence specific to KSA identified

○ No
○ Probably no
Problem Is there a problem priority? ○ Uncertain
● Probably yes
○ Yes
○ Varies
The relative importance or values of the main outcomes of interest:
○ Important uncer-
tainty or variability
Relative im- Certainty of the evidence
Is there important uncer-
○ Possibly im- Outcome
portance (GRADE)
Benefits & portant uncertainty
tainty about how much
harms of or variability Symptomatic
people value the main out- Critical Low
the options DVT
comes? ● Probably no im-
portant uncertainty PE Critical Moderate
of variability
○ No important
uncertainty of varia-
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
126

Additional con-
Criteria Research evidence
Judgements siderations

bility Summary of findings:

○ No known unde-
sirable Relative ef-
Without With Difference (95%
Outcome fect (RR)
GCS GCS CI)
(95% CI)
○ No included stud-
ies
What is the overall certain- ○ Very low Symptomatic 0/1323 0/1314
0 fewer per 1000
(from 1.5 more not estimable
ty of this evidence? DVT (0.0%) (0.0%)
● Low to 1.5 fewer)

○ Moderate
0 fewer per 1000
○ High PE
0/1323 0/1314
(from 1.5 more not estimable
(0.0%) (0.0%)
to 1.5 fewer)
○ No
● Probably no
Are the desirable anticipat-
ed effects large?
○ Uncertain
○ Probably yes
○ Yes
○ Varies
○ No
○ Probably no
Are the undesirable antici-
pated effects small?
● Uncertain
○ Probably yes
○ Yes
○ Varies
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
127

Additional con-
Criteria Research evidence
Judgements siderations

○ No
○ Probably no
Are the desirable effects
large relative to undesira- ● Uncertain
ble effects?
○ Probably yes
○ Yes
○ Varies
No evidence specific to KSA identified
○ No
● Probably no
Are the resources required
small?
○ Uncertain
○ Probably yes
○ Yes
Resource ○ Varies
use
No evidence specific to KSA identified
○ No
● Probably no
Is the incremental cost
small relative to the net ○ Uncertain
benefits?
○ Probably yes
○ Yes
○ Varies
No evidence specific to KSA identified
Equity
What would be the impact ○ Increased
on health inequities?
○ Probably in-
creased
Prophylaxis of VTE in Medical Patients and
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128

Additional con-
Criteria Research evidence
Judgements siderations

● Uncertain
○ Probably reduced
○ Reduced
○ Varies
No evidence specific to KSA identified
○ No
● Probably no
Acceptability
Is the option acceptable to
key stakeholders?
○ Uncertain
○ Probably yes
○ Yes
○ Varies
No evidence specific to KSA identified
○ No
● Probably no
Feasibility
Is the option feasible to
implement?
○ Uncertain
○ Probably yes
○ Yes
○ Varies
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
129

Recommendation
Should GCS versus no GCS be used for VTE in long distance travelers?
Undesirable consequences Undesirable consequences Desirable consequences Desirable consequences
The balance between desirable
Balance of con- clearly outweigh desirable probably outweigh desirable probably outweigh undesira- clearly outweigh undesirable
and undesirable consequences
sequences consequences in most set- consequences in most set- ble consequences in most consequences in most set-
is closely balanced or uncertain
tings tings settings tings

○ ○ ● ○ ○
We recommend against of- We suggest not offering this We recommend offering this
Type of recommendation We suggest offering this option
fering this option option option

○ ● ○ ○

In long distance high-risk travelers (>8hrs) the panel suggests not using GCS for the prevention of VTE (conditional recommendation, very
Recommendation
low quality evidence)

The panel judged the harms of GCS for prevention of VTE to probably outweigh the benefits in long distance high-risk travelers. The certainty
Justification of the evidence was considered to be very low. The panel judged the intervention to be of high cost and probably not cost effective. The panel
also judged the intervention to be neither feasible nor acceptable.

Subgroup considerations None

Implementation considera-
None
tions

Monitoring and evaluation None

Research possibilities None

Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
130

Evidence Profile: GCS compared to no GCS for VTE in long distance travelers
Bibliography (systematic reviews): Clarke M, Hopewell S, Juszczak E, Eisinga A, Kjeldstrom M. Compression stockings for preventing deep vein thrombosis in airline pas-
sengers. Cochrane Database Syst Rev . 2006; (2):CD004002.

Quality assessment № of patients Effect

Quality Importance
№ of stud- Risk of Other considera- Relative Absolute
Study design Inconsistency Indirectness Imprecision GCS no GCS
ies bias tions (95% CI) (95% CI)

Symptomatic DVT
2 1
9 randomised serious not serious not serious serious none 0/1314 0/1323 not estima- 0 fewer per 1000 (from ⨁⨁◯◯ Critical
trials (0.0%) (0.0%) ble 1.5 more to 1.5 fewer) LOW

PE
2
9 randomised serious not serious not seri- not serious none 0/1314 0/1323 not estima- 0 fewer per 1000 (from ⨁⨁⨁◯ Critical
trials ous 3 (0.0%) (0.0%) ble 1.5 more to 1.5 fewer) MODERATE

Symptomless DVT
3
9 randomised not seri- not serious serious not serious none 3/1314 47/1323 RR 0.1 32 fewer per 1000 (from ⨁⨁⨁◯ Critical
trials ous (0.2%) (3.6%) (0.04 to 27 fewer to 34 fewer) MODERATE
0.25)

Symptomless PE
4
9 randomised not seri- not serious serious not serious none 3/1314 47/1323 RR 0.1 32 fewer per 1000 (from ⨁⨁⨁◯ Critical
trials ous (0.2%) (3.6%) (0.04 to 27 fewer to 34 fewer) MODERATE
0.25)

MD – mean difference, RR – relative risk

1. Serious imprecision. Judgment made considering the absolute measures, given the relative measures were not available
2. Serious risk of bias. Studies that carried large weight for the overall effect estimate classified as high risk of bias due to lack of adequate blinding and concealment
3. Serious indirectness given the RR estimates are derived from those of a surrogate, and given the uncertainty about the baseline risks
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
131

References:

1. Kesteven P , Robinson B . Incidence of symptomatic thrombosis in a stable population of 650,000: travel and other risk factors . Aviat Space Environ
Med . 2002 ; 73 ( 6 ): 593 – 596.
2. Cannegieter SC , Doggen CJ , van Houwelingen HC , Rosendaal FR . Travel-related venous thrombosis: results from a large population-based case con-
trol study (MEGAstudy) . PLoS Med . 2006 ; 3 ( 8 ): e307 .
3. Schwarz T , Siegert G , Oettler W , et al . Venous thrombosis after long-haul flights . Arch Intern Med . 2003 ; 163 ( 22 ):2759 - 2764 .
4. Arfvidsson B , Eklof B , Kistner RL , Masuda EM , Sato DT .Risk factors for venous thromboembolism following prolonged air travel. Coach class throm-
bosis . Hematol Oncol Clin North Am . 2000 ; 14 ( 2 ): 391 - 400; ix .
5. Martinelli I , Taioli E , Battaglioli T , et al . Risk of venous thromboembolism after air travel: interaction with thrombophilia and oral contraceptives .
Arch Intern Med . 2003 ; 163 ( 22 ): 2771 - 2774 .
6. Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ ; American College of Chest Physicians. Executive summary: antithrombotic therapy
and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest . 2012 141(2)(suppl):7S-
47S.
7. Lapostolle F , Surget V , Borron SW , et al . Severe pulmonary embolism associated with air travel . N Engl J Med . 2001 ; 345 ( 11 ): 779 - 783 .
8. Hughes RJ , Hopkins RJ , Hill S , et al . Frequency of venous thromboembolism in low to moderate risk long distance air travellers: the New Zealand Air
Traveller’s Thrombosis
9. Hughes RJ1, Hopkins RJ, Hill S, Weatherall M, Van de Water N, Nowitz M, Milne D, Ayling J, Wilsher M, Beasley R. Frequency of venous thromboembo-
lism in low to moderate risk long distance air travellers: the New Zealand Air Traveller's Thrombosis (NZATT) study. Lancet. 2003 Dec
20;362(9401):2039-44.
10. Philbrick JT , Shumate R , Siadaty MS , Becker DM . Air travel and venous thromboembolism: a systematic review . J Gen Intern Med . 2007 ; 22 ( 1 ):
107 - 114 .
11. Schwarz T , Siegert G , Oettler W , et al . Venous thrombosis after long-haul flights . Arch Intern Med . 2003 ; 163 ( 22 ): 2759 - 2764 .
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
132

Appendix 2: Search Strategies and Results

Benefits & Harms Searches:

Data base: Medline

Search strategy: VTE in long distance travelers Date of search: February 2015
1. exp Venous Thrombosis/
2. deep venous thromb$.mp.
3. Venous Thromboembolism/
4. Pulmonary embolism/
5. (PE or DVT or VTE:ti,ab,kw).mp. [mp=title, abstract, original title, name of substance word, subject
heading word, keyword heading word, protocol supplementary concept word, rare disease supplemen-
tary concept word, unique identifier]
6. ((Pulmon$ or vein or venous) adj3 (Emboli$ or thromb$)).mp.
7. (thromboprophyla* or thrombus* or thrombotic* or throm- bolic* or thromboemboli* or thrombos*
or embol*).mp. [mp=title, abstract, original title, name of substance word, subject heading word, key-
word heading word, protocol supplementary concept word, rare disease supplementary concept word,
unique identifier]
8. 1 or 2 or 3 or 4 or 5 or 6 or 7
9. (air adj3 travel).mp.
10. flight.mp.
11. flying.mp.
12. aircraft.mp.
13. aerospace medicine.mp.
14. 9 or 10 or 11 or 12 or 13
15. 8 and 14
16. limit 15 to yr="2009 -Current"
Records Retrieved 268

Benefits & Harms Searches:

Data base: Medline

Search strategy: General VTE Date of search: February 2015
1. exp Venous Thrombosis/
2. deep venous thromb$.mp.
3. Venous Thromboembolism/
4. Pulmonary embolism/
5. (PE or DVT or VTE:ti,ab,kw).mp. [mp=title, abstract, original title, name of substance word, subject
heading word, keyword heading word, protocol supplementary concept word, rare disease supplemen-
tary concept word, unique identifier]
6. ((Pulmon$ or vein or venous) adj3 (Emboli$ or thromb$)).mp.
7. (thromboprophyla* or thrombus* or thrombotic* or throm- bolic* or thromboemboli* or thrombos*
or embol*).mp. [mp=title, abstract, original title, name of substance word, subject heading word, key-
word heading word, protocol supplementary concept word, rare disease supplementary concept word,
unique identifier]
8. 1 or 2 or 3 or 4 or 5 or 6 or 7
9. Primary prevention.mp. or primary prevention/
10. Thromboprophylaxis$.mp.
11. prophylax$.mp.
12. prevent*.mp.
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
133

13. or/9-12
14. anticoagulant$.mp. or exp Anticoagulants/
15. exp Heparin/ or heparin.mp.
16. exp Heparin, Low-Molecular-Weight/
17. (LMW or low molecular weight heparin or nadroparin or fraxiparin or enoxaparin or clexane or love-
nox or dalteparin or fragmin or ardeparin or normiflo or tinzaparin or logiparin or innohep or certoparin
or sandoparin or reviparin or clivarin or danaproid or orgaran).mp.
18. 14 or 15 or 16 or 17
19. pneumatic compression.mp.
20. mechanical compression.mp.
21. mechanical thromboprophylaxis.mp.
22. Mechanical Thrombolysis.mp. or Mechanical Thrombolysis/
23. (intermittent pneumatic compression device or Intermittent Pneumatic Compression Devices or Com-
pression or stocking$).mp. [mp=title, abstract, original title, name of substance word, subject heading
word, keyword heading word, protocol supplementary concept word, rare disease supplementary con-
cept word, unique identifier]
24. 19 or 20 or 21 or 22 or 23
25. 18 or 24
26. randomized controlled trial.pt.
27. controlled clinical trial.pt.
28. randomized.ab.
29. placebo.ab.
30. clinical trials as topic.sh.
31. randomly.ab.
32. trial.ti.
33. 26 or 27 or 28 or 29 or 30 or 31 or 32
34. exp animals/ not humans.sh.
35. 33 not 34
36. 8 and 13 and 25 and 33 and 35
37. limit 36 to yr="2009 -Current"
Records Retrieved 1036

Data base: Embase

Search strategy: VTE in long distance travelers Date of search: February 2014
1. 'deep vein thrombosis'/
2. deep venous thromb$.mp.
3. Venous Thromboembolism/
4. 'lung embolism'/
5. (PE or DVT or VTE:ti,ab,kw).mp. [mp=title, abstract, subject headings, heading word, drug trade name,
original title, device manufacturer, drug manufacturer, device trade name, keyword]
6. ((Pulmon$ or vein or venous) adj3 (Emboli$ or thromb$)).mp.
7. (thromboprophyla* or thrombus* or thrombotic* or throm- bolic* or thromboemboli* or thrombos*
or embol*).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, de-
vice manufacturer, drug manufacturer, device trade name, keyword]
8. 1 or 2 or 3 or 4 or 5 or 6 or 7
9. (air adj3 travel).mp.
10. flight.mp.
11. flying.mp.
12. aircraft.mp.
13. aerospace medicine.mp.
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
134

14. 9 or 10 or 11 or 12 or 13
15. Primary prevention.mp. or 'primary prevention'/
16. Thromboprophylaxis$.mp.
17. prophylax$.mp.
18. prevent*.mp.
19. 15 or 16 or 17 or 18
20. 8 and 14 and 19
21. limit 20 to yr="2009 -Current"
Records Retrieved 38

Data base: Embase

Search strategy: General VTE Date of search: February 2015
1. exp deep vein thrombosis/
2. deep venous thromb$.mp.
3. Venous Thromboembolism/
4. 'lung embolism'/
5. (PE or DVT or VTE:ti,ab,kw).mp. [mp=title, abstract, subject headings, heading word, drug trade name,
original title, device manufacturer, drug manufacturer, device trade name, keyword]
6. ((Pulmon$ or vein or venous) adj3 (Emboli$ or thromb$)).mp.
7. (thromboprophyla* or thrombus* or thrombotic* or throm- bolic* or thromboemboli* or thrombos*
or embol*).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, de-
vice manufacturer, drug manufacturer, device trade name, keyword]
8. or/1-7
9. Primary prevention.mp. or 'primary prevention'/
10. Thromboprophylaxis$.mp.
11. prophylax$.mp.
12. prevent*.mp.
13. or/9-12
14. anticoagulant$.mp. or exp 'anticoagulant agent'/
15. 'heparin'/exp or heparin.mp.
16. 'low molecular weight heparin'/
17. (LMW or low molecular weight heparin or nadroparin or fraxiparin or enoxaparin or clexane or love-
nox or dalteparin or fragmin or ardeparin or normiflo or tinzaparin or logiparin or innohep or certoparin
or sandoparin or reviparin or clivarin or danaproid or orgaran).mp.
18. 14 or 15 or 16 or 17
19. pneumatic compression.mp.
20. mechanical compression.mp.
21. mechanical thromboprophylaxis.mp.
22. Mechanical Thrombolysis.mp. or 'mechanical thrombectomy'/
23. (intermittent pneumatic compression device or Intermittent Pneumatic Compression Devices or
stocking or stocking$).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original
title, device manufacturer, drug manufacturer, device trade name, keyword]
24. (intermittent pneumatic compression device or Intermittent Pneumatic Compression Devices or
stocking or stocking$).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original
title, device manufacturer, drug manufacturer, device trade name, keyword]
25. or/19-24
26. 18 or 25
27. Clinical trial/
28. Randomized controlled trial/
29. Randomization/
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
135

30. Single blind procedure/

31. Double blind procedure/
32. Crossover procedure/
33. Placebo/
34. Randomi?ed controlled trial$.tw.
35. Rct.tw.
36. Random allocation.tw.
37. Randomly allocated.tw.
38. Allocated randomly.tw.
39. (allocated adj2 random).tw.
40. Single blind$.tw.
41. Double blind$.tw.
42. ((treble or triple) adj blind$).tw.
43. Placebo$.tw.
44. Prospective study/
45. or/27-44
46. Case study/
47. Case report.tw.
48. Abstract report/ or letter/
49. 46 or 47 or 48
50. 45 not 49
51. exp animals/ not humans.sh.
52. 50 not 51
53. 8 and 13 and 26 and 45 and 52
54. limit 53 to yr="2009 -Current"
Records Retrieved 898

Data base: Central

Search strategy: VTE in long distance travelers Date of search: February 2015
#1 MeSH descriptor: [Venous Thrombosis] explode all trees
#2 deep venous thromb*
#3 MeSH descriptor: [Venous Thromboembolism] explode all trees
#4 MeSH descriptor: [Pulmonary Embolism] explode all trees
#5 PE or DVT or VTE
#6 ((Pulmon$ or vein or venous) adj3 (Emboli$ or thromb$))
#7 (thromboprophyla* or thrombus* or thrombotic* or throm- bolic* or thromboemboli* or throm-
bos* or embol*)
#8 #1 or #2 or #3 or #4 or #5 or #6 or #7
#9 MeSH descriptor: [Primary Prevention] explode all trees
#10 Thromboprophylaxis
#11 prophylax*
#12 prevent*
#13 #9 or #10 or #11 or #12
#14 (air adj3 travel)
#15 flight
#16 flying
#17 aircraft
#18 aerospace medicine
#19 #14 or #15 or #16 or #17 or #18
#20 #8 and #13 and #19 Publication Year from 2009 to 2014
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
136

Records Retrieved 28

Data base: Central

Search strategy: VTE in general Date of search: February 2015
#1 MeSH descriptor: [Venous Thrombosis] explode all trees
#2 deep venous thromb*
#3 MeSH descriptor: [Venous Thromboembolism] explode all trees
#4 MeSH descriptor: [Pulmonary Embolism] explode all trees
#5 PE or DVT or VTE
#6 ((Pulmon$ or vein or venous) adj3 (Emboli$ or thromb$))
#7 (thromboprophyla* or thrombus* or thrombotic* or throm- bolic* or thromboemboli* or throm-
bos* or embol*)
#8 #1 or #2 or #3 or #4 or #5 or #6 or #7
#9 MeSH descriptor: [Primary Prevention] explode all trees
#10 Thromboprophylaxis
#11 prophylax*
#12 prevent*
#13 #9 or #10 or #11 or #12
#14 MeSH descriptor: [Anticoagulants] explode all trees
#15 MeSH descriptor: [Heparin] explode all trees
#16 MeSH descriptor: [Heparin, Low-Molecular-Weight] explode all trees
#17 (LMW or low molecular weight heparin or nadroparin or fraxiparin or enoxaparin or clexane or
lovenox or dalteparin or fragmin or ardeparin or normiflo or tinzaparin or logiparin or innohep or
certoparin or sandoparin or reviparin or clivarin or danaproid or orgaran)
#18 #14 or #15 or #16 or #17
#19 pneumatic compression
#20 mechanical compression
#21 MeSH descriptor: [Mechanical Thrombolysis] explode all trees
#22 intermittent pneumatic compression device or Intermittent Pneumatic Compression Devices or
stocking
#23 #19 or #20 or #21 or #22
#24 #8 and #13 and #18 and #23 Publication Year from 2009 to 2014
Records Retrieved 73

Summary of Searches: Benefits & Harms

Total No. Retrieved: 2007

Medline: 1304
Embase: 936
Cochrane: 101
Duplicates: 946
Title & abstract 1395
without duplicates:
Full text: 716
Included: 38
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
137

Patients’ Values and Preferences Searches

Data base: Medline

Search strategy: Date of search: December 2014

1. exp Venous Thrombosis/

2. deep venous thromb$.mp.
3. Venous Thromboembolism/
4. Pulmonary embolism/
5. ((Pulmon$ or vein or venous) adj3 (Emboli$ or thromb$)).mp.
6. 1 or 2 or 3 or 4 or 5
7. Primary Prevention.mp. or Primary Prevention/
8. Thromboprophylax$.mp.
9. prophylax$.mp.
10. 7 or 8 or 9
11. 6 and 10
12. Stocking$, Compression/ or stocking.mp.
13. pneumatic compression.mp.
14. mechanical compression.mp.
15. mechanical thromboprophylaxis.mp.
16. Mechanical Thrombolysis.mp. or Mechanical Thrombolysis/
17. intermittent pneumatic compression device.mp. or Intermittent Pneumatic Compression Devices/
18. 12 or 13 or 14 or 15 or 16 or 17
19. anticoagulant$.mp. or exp Anticoagulants/
20. exp Heparin/ or heparin.mp.
21. exp Heparin, Low-Molecular-Weight/
22. (LMW or low molecular weight heparin or nadroparin or fraxiparin or enoxaparin or clexane or love-
nox or dalteparin or fragmin or ardeparin or normiflo or tinzaparin or logiparin or innohep or certoparin
or sandoparin or reviparin or clivarin or danaproid or orgaran).mp.
23. 19 or 20 or 21 or 22
24. 18 or 23
25. 11 and 24
26. patient$ participation.mp. or exp patient participation/
27. patient$ satisfaction.mp. or exp patient satisfaction/
28. attitude to health.mp. or exp Attitude to health/
29. (patient$ preference$ or patient$ perception$ or patient$ decision$ or patient$ perspective$ or user$
view$ or patient$ view$ or patient$ value$).mp.
30. health related quality of life.mp. or exp "quality of life"/
31. (health stat$ utilit$ or health stat$ indicator$ or (health stat$ adj 2 valu$)).mp. or exp Health Status
Indicators/
32. 26 or 27 or 28 or 29 or 30 or 31
33. 25 and 32
34. Saudi Arab$.mp,in. or Saudi Arabia/
35. Riyadh.mp,in.
36. Jeddah.mp,in.
37. Saudi Arab$.mp,in. or Saudi Arabia/
38. Riyadh.mp,in.
39. Jeddah.mp,in.
40. Kh*bar.mp,in.
41. Dammam.mp,in.
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
138

42. 37 or 38 or 39 or 40 or 41
43. Kuwait$.mp,in. or Kuwait/
44. United Arab Emirates.mp,in. or United Arab Emirates/
45. Qatar$.mp,in. or Qatar/
46. Oman$.mp,in. or Oman/
47. Yemen$.mp,in. or Yemen/
48. Bahr*in$.mp,in. or Bahrain/
49. 43 or 44 or 45 or 46 or 47 or 48
50. Middle East$.mp,in. or Middle East/
51. Jordan$.mp,in. or Jordan/
52. Libya$.mp,in. or Libya/
53. Egypt$.mp,in. or Egypt/
54. Syria$.mp,in. or Syria/
55. Iraq$/ or Iraq.mp,in.
56. Morocc$.mp,in. or Morocco/
57. Tunisia$.mp,in. or Tunisia/
58. Leban$.mp,in. or Lebanon/
59. West Bank.mp,in.
60. Iran$.mp,in. or Iran/
61. Turkey/ or (Turkey or Turkish).mp,in.
62. Algeria$.mp,in. or Algeria/
63. Arab$.mp,in. or Arabs/
64. 50 or 51 or 52 or 53 or 54 or 55 or 56 or 57 or 58 or 59 or 60 or 61 or 62
65. 63 or 64
66. 42 or 49 or 65
67. 33 and 66
68. limit 67 to yr="2009 - 2014"
69. remove duplicates from 68

Records Retrieved 180

Data base: Embase

Search strategy: Date of search: December 2014
1. Saudi Arab$.mp,in. or Saudi Arabia/
2. Riyadh.mp,in.
3. Jeddah.mp,in.
4. Saudi Arab$.mp,in. or Saudi Arabia/
5. Riyadh.mp,in.
6. Jeddah.mp,in.
7. Kh*bar.mp,in.
8. Dammam.mp,in.
9. 4 or 5 or 6 or 7 or 8
10. Kuwait$.mp,in. or Kuwait/
11. United Arab Emirates.mp,in. or United Arab Emirates/
12. Qatar$.mp,in. or Qatar/
13. Oman$.mp,in. or Oman/
14. Yemen$.mp,in. or Yemen/
15. Bahr*in$.mp,in. or Bahrain/
16. 10 or 11 or 12 or 13 or 14 or 15
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
139

17. Middle East$.mp,in. or Middle East/

18. Jordan$.mp,in. or Jordan/
19. Libya$.mp,in. or Libya/
20. Egypt$.mp,in. or Egypt/
21. Syria$.mp,in. or Syria/
22. Iraq$/ or Iraq.mp,in.
23. Morocc$.mp,in. or Morocco/
24. Tunisia$.mp,in. or Tunisia/
25. Leban$.mp,in. or Lebanon/
26. West Bank.mp,in.
27. Iran$.mp,in. or Iran/
28. Turkey/ or (Turkey or Turkish).mp,in.
29. Algeria$.mp,in. or Algeria/
30. Arab$.mp,in. or Arabs/
31. 17 or 18 or 19 or 20 or 21 or 22 or 23 or 24 or 25 or 26 or 27 or 28 or 29
32. 30 or 31
33. 9 or 16 or 32
34. patient$ participation.mp. or exp patient participation/
35. patient$ satisfaction.mp. or exp patient satisfaction/
36. attitude to health.mp. or exp Attitude to health/
37. (patient$ preference$ or patient$ perception$ or patient$ decision$ or patient$ perspective$ or user$
view$ or patient$ view$ or patient$ value$).mp.
38. (patient$ utilit$ or health utilit$).mp.
39. health related quality of life.mp. or exp "quality of life"/
40. (health stat$ utilit$ or health stat$ indicator$ or (health stat$ adj 2 valu$)).mp. or exp Health Status
Indicators/
41. 34 or 35 or 36 or 37 or 38 or 39 or 40
42. Venous Thromboembol$.mp. or venous thromboembolism/
43. deep vein thrombosis/ or (deep adj (venous or vein) adj thromb$).mp.
44. lung embolism/
45. ((Pulmon$ or lung or vein or venous) adj3 (Emboli$ or thromb$)).mp.
46. exp vein thrombosis/
47. 42 or 43 or 44 or 45 or 46
48. Primary Prevention.mp. or primary prevention/
49. prophylaxis/ or thrombosis prevention/
50. (prophyla$ or thromb$ prevention).mp.
51. 48 or 49 or 50
52. compression stocking/ or Stocking$.mp. or exp compression therapy/
53. pneumatic compression.mp.
54. intermittent pneumatic compression device/
55. (Mechanical adj (thrombectomy or Thrombolysis)).mp. or mechanical thrombectomy/
56. 52 or 53 or 54 or 55
57. anticoagulant$.mp. or anticoagulant agent/
58. low molecular weight heparin/ or heparin/ or Heparin$.mp.
59. (LMW or low molecular weight heparin or nadroparin or fraxiparin or enoxaparin or clexane or love-
nox or dalteparin or fragmin or ardeparin or normiflo or tinzaparin or logiparin or innohep or certoparin
or sandoparin or reviparin or clivarin or danaproid or orgaran).mp.
60. 57 or 58 or 59
61. 56 or 60
62. 47 and 51 and 61
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
140

63. 33 and 41 and 62

64. limit 63 to yr="2009 - 2014"
65. remove duplicates from 64

Records Retrieved 204

Summary of Searches: Patients’ Values and Preferences

Total No. Retrieved: 384
Medline: 180
Embase: 204
Duplicates: 199
Title & Abstract 185
without duplicates:
Full text: 51

Included: 4

Cost-Effectiveness Search:

Data base: Medline

Search strategy: Date of search: December 2014

1. Saudi Arab$.mp,in. or Saudi Arabia/

2. Riyadh.mp,in.
3. Jeddah.mp,in.
4. Kh*bar.mp,in.
5. Dammam.mp,in.
6. 1 or 2 or 3 or 4 or 5
7. Kuwait$.mp,in. or Kuwait/
8. Saudi Arab$.mp,in. or Saudi Arabia/
9. Riyadh.mp,in.
10. Jeddah.mp,in.
11. Kh*bar.mp,in.
12. Dammam.mp,in.
13. 8 or 9 or 10 or 11 or 12
14. Kuwait$.mp,in. or Kuwait/
15. United Arab Emirates.mp,in. or United Arab Emirates/
16. Qatar$.mp,in. or Qatar/
17. Oman$.mp,in. or Oman/
18. Yemen$.mp,in. or Yemen/
19. Bahr*in$.mp,in. or Bahrain/
20. 14 or 15 or 16 or 17 or 18 or 19
21. Middle East$.mp,in. or Middle East/
22. Jordan$.mp,in. or Jordan/
23. Libya$.mp,in. or Libya/
24. Egypt$.mp,in. or Egypt/
25. Syria$.mp,in. or Syria/
26. Iraq$/ or Iraq.mp,in.
27. Morocc$.mp,in. or Morocco/
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
141

28. Tunisia$.mp,in. or Tunisia/

29. Leban$.mp,in. or Lebanon/
30. West Bank.mp,in.
31. Iran$.mp,in. or Iran/
32. Turkey/ or (Turkey or Turkish).mp,in.
33. Algeria$.mp,in. or Algeria/
34. Arab$.mp,in. or Arabs/
35. 21 or 22 or 23 or 24 or 25 or 26 or 27 or 28 or 29 or 30 or 31 or 32 or 33
36. 34 or 35
37. 13 or 20 or 36
38. exp Venous Thrombosis/
39. deep venous thromb$.mp.
40. Venous Thromboembolism/
41. Pulmonary embolism/
42. ((Pulmon$ or vein or venous) adj3 (Emboli$ or thromb$)).mp.
43. 38 or 39 or 40 or 41 or 42
44. Primary Prevention.mp. or Primary Prevention/
45. Thromboprophylax$.mp.
46. prophylax$.mp.
47. 44 or 45 or 46
48. 43 and 47
49. Stocking$, Compression/ or stocking.mp.
50. pneumatic compression.mp.
51. mechanical compression.mp.
52. mechanical thromboprophylaxis.mp.
53. Mechanical Thrombolysis.mp. or Mechanical Thrombolysis/
54. intermittent pneumatic compression device.mp. or Intermittent Pneumatic Compression Devices/
55. 49 or 50 or 51 or 52 or 53 or 54
56. anticoagulant$.mp. or exp Anticoagulants/
57. exp Heparin/ or heparin.mp.
58. exp Heparin, Low-Molecular-Weight/
59. (LMW or low molecular weight heparin or nadroparin or fraxiparin or enoxaparin or clexane or love-
nox or dalteparin or fragmin or ardeparin or normiflo or tinzaparin or logiparin or innohep or certoparin
or sandoparin or reviparin or clivarin or danaproid or orgaran).mp.
60. 56 or 57 or 58 or 59
61. 55 or 60
62. 48 and 61
63. economics/ or exp economics, hospital/ or exp economics, medical/ or economics, nursing/ or eco-
nomics, pharmaceutical/
64. exp "Costs and Cost Analysis"/
65. Value-Based Purchasing/
66. exp "Fees and Charges"/
67. budget$.mp. or Budgets/
68. (low adj cost).mp.
69. (high adj cost).mp.
70. (health?care adj cost$).mp.
71. (cost adj estimate$).mp.
72. (cost adj variable$).mp.
73. (unit adj cost$).mp.
74. (fiscal or funding or financial or finance).tw.
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
142

75. (economic$ or pharmacoeconomic$ or price$ or pricing).tw.

76. 63 or 64 or 65 or 66 or 67 or 68 or 69 or 70 or 71 or 72 or 73 or 74 or 75
77. 37 and 62 and 76
78. limit 77 to yr="2009 - 2014"
79. remove duplicates from 78
Records Retrieved 347

Data base: Embase

Search strategy: Date of search: December 2014

1. Saudi Arab$.mp,in. or Saudi Arabia/

2. Riyadh.mp,in.
3. Jeddah.mp,in.
4. Saudi Arab$.mp,in. or Saudi Arabia/
5. Riyadh.mp,in.
6. Jeddah.mp,in.
7. Kh*bar.mp,in.
8. Dammam.mp,in.
9. 4 or 5 or 6 or 7 or 8
10. Kuwait$.mp,in. or Kuwait/
11. United Arab Emirates.mp,in. or United Arab Emirates/
12. Qatar$.mp,in. or Qatar/
13. Oman$.mp,in. or Oman/
14. Yemen$.mp,in. or Yemen/
15. Bahr*in$.mp,in. or Bahrain/
16. 10 or 11 or 12 or 13 or 14 or 15
17. Middle East$.mp,in. or Middle East/
18. Jordan$.mp,in. or Jordan/
19. Libya$.mp,in. or Libya/
20. Egypt$.mp,in. or Egypt/
21. Syria$.mp,in. or Syria/
22. Iraq$/ or Iraq.mp,in.
23. Morocc$.mp,in. or Morocco/
24. Tunisia$.mp,in. or Tunisia/
25. Leban$.mp,in. or Lebanon/
26. West Bank.mp,in.
27. Iran$.mp,in. or Iran/
28. Turkey/ or (Turkey or Turkish).mp,in.
29. Algeria$.mp,in. or Algeria/
30. Arab$.mp,in. or Arabs/
31. 17 or 18 or 19 or 20 or 21 or 22 or 23 or 24 or 25 or 26 or 27 or 28 or 29
32. 30 or 31
33. 9 or 16 or 32
34. patient$ participation.mp. or exp patient participation/
35. patient$ satisfaction.mp. or exp patient satisfaction/
36. attitude to health.mp. or exp Attitude to health/
37. (patient$ preference$ or patient$ perception$ or patient$ decision$ or patient$ perspective$ or user$
view$ or patient$ view$ or patient$ value$).mp.
38. (patient$ utilit$ or health utilit$).mp.
39. health related quality of life.mp. or exp "quality of life"/
Prophylaxis of VTE in Medical Patients and
Long Distance Travelers
143

40. (health stat$ utilit$ or health stat$ indicator$ or (health stat$ adj 2 valu$)).mp. or exp Health Status
Indicators/
41. 34 or 35 or 36 or 37 or 38 or 39 or 40
42. Venous Thromboembol$.mp. or venous thromboembolism/
43. deep vein thrombosis/ or (deep adj (venous or vein) adj thromb$).mp.
44. lung embolism/
45. ((Pulmon$ or lung or vein or venous) adj3 (Emboli$ or thromb$)).mp.
46. exp vein thrombosis/
47. 42 or 43 or 44 or 45 or 46
48. Primary Prevention.mp. or primary prevention/
49. prophylaxis/ or thrombosis prevention/
50. (prophyla$ or thromb$ prevention).mp.
51. 48 or 49 or 50
52. compression stocking/ or Stocking$.mp. or exp compression therapy/
53. pneumatic compression.mp.
54. intermittent pneumatic compression device/
55. (Mechanical adj (thrombectomy or Thrombolysis)).mp. or mechanical thrombectomy/
56. 52 or 53 or 54 or 55
57. anticoagulant$.mp. or anticoagulant agent/
58. low molecular weight heparin/ or heparin/ or Heparin$.mp.
59. (LMW or low molecular weight heparin or nadroparin or fraxiparin or enoxaparin or clexane or love-
nox or dalteparin or fragmin or ardeparin or normiflo or tinzaparin or logiparin or innohep or certoparin
or sandoparin or reviparin or clivarin or danaproid or orgaran).mp.
60. 57 or 58 or 59
61. 56 or 60
62. 47 and 51 and 61
63. 33 and 41 and 62
64. limit 63 to yr="2009 - 2014"
65. remove duplicates from 64

Records Retrieved 600

Summary of Searches: Cost-Effectiveness

Total No. Retrieved: 947

Medline: 347
Embase: 600
Duplicates: 580
Title and abstract 362
without duplicates:
Full text: 51
Included: 8