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Review article

Epidemiology, risk factors and sequelae of venous


thromboembolism

P Wong* and T Baglin†


*Freeman Hospital, Newcastle-upon-Tyne; †Addenbrooke’s Hospital, Cambridge, UK

Abstract
The aim of this review was to discuss the epidemiology, risk factors and sequelae of venous
thromboembolism (VTE). VTE has an incidence of 1– 2 per 1000 people annually. The risk of
VTE increases with age and is highest in Caucasians and African Americans. Combined oral
contraceptives (COC), especially the third-generation COCs, have been strongly implicated
in VTE. Hospitalized patients, especially patients with underlying malignancy and
undergoing surgery, have a host of risk factors for VTE. Thrombophilia can predispose an
individual to VTE but indiscriminate testing for thrombophilia in patients presenting with
VTE is not indicated. VTE can have serious chronic sequelae in the form of post-
thrombotic syndrome (PTS) and chronic thromboembolic pulmonary hypertension
(CTPH). The risk of PTS and CTPH is increased with recurrent deep vein thrombosis and
pulmonary embolism, respectively. Mortality from VTE can be as high as 21.6% at one
year. Patients who had an episode of VTE have a high risk of subsequent VTE and this
risk is highest in patients who had a first VTE event associated with malignancy. A good
understanding of the epidemiology and risk factors of VTE will enable the treating
medical practitioners to identify patients at risk and administer appropriate VTE
prophylaxis to prevent the long-term consequences of VTE.

Keywords: venous; thromboembolism; epidemiology; risk factors; sequelae

Introduction the immediate cause of up to 10% of hospital


deaths in postmortem studies.3,4
Deep vein thrombosis (DVT) and pulmonary embo-
lism (PE) are both manifestations of the same
disease process of venous thromboembolism Epidemiology
(VTE). DVT has been reported as the most Detailed annual incidence of VTE is hard to obtain
common preventable cause of hospital-related because VTE is often clinically silent and in many
death.1 The UK House of Commons Health Com- cases, the first sign of the disease is a sudden fatal
mittee reported that an estimated 25,000 patients PE.5,6 The overall incidence of VTE is estimated at
in England die each year from preventable 1 – 2 per 1000 annually.7 – 9 About two-thirds of
hospital-acquired VTE,2 more than the combined VTE episodes manifest as DVT and one-third as
deaths from breast cancer, AIDS and road traffic PE with or without DVT. Studies that include a
injuries, and more than 25 times the number of large number of VTE cases diagnosed by autopsy
deaths from methicillin-resistant Staphylococcus generally report a higher proportion of cases with
aureus (MRSA). In addition, VTE was found to be PE than DVT. The VTE Impact Assessment Group
in Europe (VITAE) highlighted that epidemiological
studies of diagnosed VTE underestimated the
Correspondence: P Wong MB ChB, Department of Vascular
Surgery, Freeman Hospital, High Heaton, Newcastle-upon- burden of disease as many cases are undiagnosed
Tyne NE7 7DN, UK. and studies do not include unrecognized
Email: pwong23@hotmail.com thrombosis-related deaths.10 Based on their statisti-
cal modelling, the annual mortality due to
Accepted 31 January 2012 hospital-acquired VTE is about one in 1150 of the

Phlebology 2012;27 Suppl 2:2–11. DOI: 10.1258/phleb.2012.012S31


P Wong and T Baglin. Epidemiology, risk factors and sequelae of VTE Review article

population in six of the European countries studied. with a thousand-fold increase in risk from the
When compared with the annual incidence of VTE very young to the very old.8,18 – 20 It is extremely
of 1– 2 per 1000, the VITAE calculations suggest that uncommon in childhood (1 in 100,000 per year),
almost as many patients die of VTE as are diag- increases to one per 10,000 annually before the
nosed, with about 85% of these deaths occurring fourth decade of life and rises to nearly 1% per
without the diagnosis being suspected in life.10 year in old age.8,9,18,19 The risk increases signifi-
This estimate is compatible with the finding of post- cantly after age 45 years and approaches 5 – 6 per
mortem studies that showed that about 85% of 1000 annually by age 80.15 In fact, the eight-year
deaths in hospital due to hospital-acquired VTE rate among those aged 85 years and older at
occur without a diagnosis of VTE before death baseline was 13 times greater than in those aged
(Table 1).3 – 5,11,12 Studies of VTE with autopsy data 45– 55.21
have to be interpreted with caution as they often The reason for this is unclear but may be attribu-
include cases with asymptomatic PE, failing to ted to several factors such as decreased mobility, an
take into account other causes of death, thereby increased presence of other illnesses predisposing
overestimating the incidence.13 Conversely, studies to thrombosis, increase in coagulation potential or
that rely on clinical diagnosis often underestimate a combination of these factors.22
the incidence.
The average annual incidence of in-hospital DVT
was reported to range from 48 per 100,000 to 87 per Gender
100,000.8,10,14,15 In a retrospective review, the
Men and women are affected about equally by VTE
average annual age- and sex-adjusted incidence of
with slightly higher rates among women in the
in-hospital VTE was noted to be 100 times greater
younger age groups due to the increased thrombo-
than the incidence among community residents.16
sis effects of oral contraceptives, pregnancy and
Combined with community-acquired DVT, the
puerperium.8,9,15,19 The relative risks of VTE
annual incidence of total DVT in the European
among women using oral contraceptives or
Union (EU) was estimated to be 148 per 100,000 and
hormone replacement therapy is around 2 – 4 com-
this translates into 684,019 DVT events in the EU
pared with non-users.23 – 25
per annum.10 The annual in-hospital PE was reported
to range between 23 per 100,000 and 69 per
100,000.8,14,15 The VITAE study estimated that up to
Race
434,723 PE events and up to 543,454 VTE-related
deaths occur per annum. In the USA, it was estimated There are variations in the incidence of diagnosed
that more than 900,000 incident or recurrent, fatal and VTE among ethnic groups. Compared with Cauca-
non-fatal VTE events occur annually, with up to a sians, African Americans have an incidence of
third resulting in fatality.17 In the UK, this equates to VTE approximately 25% higher,21,26 while Asians,
approximately 59,000 new cases of DVT and 29,500 Native Americans, Pacific Islanders and Hispanics
new cases of non-fatal PE per year.2 have an incidence almost 70% lower.26 – 28 A poss-
ible explanation for the lower rates of VTE in
Asian populations is due to the lower prevalence
Age
of genetic factors predisposing to VTE such as
The risk of VTE increases exponentially with factor V Leiden or prothrombin F2G20210A
age14,15 and is the strongest risk factor for VTE mutation.29 – 31 The higher incidence of VTE in

Table 1 Postmortem (PM) studies recording deaths due to pulmonary embolism (PE)

Author (year) Number of PMs (rate) Total PE at PM Deaths attributable Proportion of fatal cases with venous
to PE at PM thrombosis not suspected in life

Sandler (1989)3 2388 (47%) 313 (13%) 239 (10%) 95%


Lindblad (1991)4 994 (77% in final year 260 (26%) 93 (9.4%) –
of study)
Stein (1995)5 404 (–) 59 (15%) 20 (5.0%) 70%
Baglin (1997)12 400 (–) 45 (11.25%) 29 (7.25%) 90%
Alikhan (2004)11 5107 (42%) – 265 (5.2%) –
Total 9293 – 646
7% (95% CI 6.4– 7.5)

CI, confidence interval

Phlebology 2012;27 Suppl 2:2–11 3


Review article P Wong and T Baglin. Epidemiology, risk factors and sequelae of VTE

African Americans could be explained by the Table 2 Risk factors for venous thromboembolism
higher levels of haemostatic markers of thrombosis Inherited Acquired
risk, including factor VIII, von Willebrand factor
and D-dimer.32 Antithrombin deficiency Immobilization
Protein C deficiency Surgery
Protein S deficiency Trauma
Factor V Leiden Acute medical illness
Seasonal variation Prothrombin G20210A Increasing age
Various studies and meta-analyses have demon- Elevated factor VIII levels Pregnancy and puerperium
Factor XIII 34val Oestrogen containing oral contra-
strated an increased incidence of VTE of 14%33 Fibrinogen (G) 10034T ceptive or hormonal replacement
and fatal PE during the winter months.34,35 The Dysfibrinogenaemia therapy
mechanism is still unclear but may possibly be Previous VTE
due to a decrease in physical activity during the Malignancy
winter months. Cancer therapies (hormonal, che-
motherapy or radiotherapy)
Antiphospholipid syndrome
Myeloproliferative disorders
Risk factors Polycythaemia rubra vera
Heart or respiratory failure
Virchow’s triad described in the 1860s remains a Inflammatory bowel disease
valid concept in the aetiology of VTE. Any altera- Stroke
tions in the blood flow (stasis), composition Nephrotic syndrome
Haemoglobinopathies
of blood (hypercoagulability) and vessel wall Paroxysmal nocturnal
(venous injury) could lead to thrombosis. VTE is haemoglobinuria
therefore a multifactorial disorder and could arise Paraproteinaemia
due to either inherited conditions or acquired pre- Obesity
dispositions (see Table 2). Smoking
Varicose veins
Central venous lines
Obesity VTE, venous thromboembolism
Obesity, defined as body mass index (BMI) more
than 30 kg/m2 is associated with a two-to-threefold ation.41 The risk of VTE is not increased with use
increased risk of VTE.21,36 Severe obesity (BMI . of progestogen-only pills or hormone-releasing
40 kg/m2) has an even higher associated risk of intrauterine devices.42 Users of hormone replace-
VTE.22 The mechanism of the increased risk is not ment therapy have been shown to have an
well defined but may be due to impaired venous increased risk of VTE compared with non-users.43
return due to the physical aspects of body size; Similarly, men receiving oestrogen therapy for pros-
and that biochemical parameters associated with tate cancer should also be warned of the increased
obesity, for example, increased coagulation and risks of VTE.44
inflammation, may play a role.22

Hormone therapy Hospitalization


Oral contraceptives have been associated with an Most patients admitted to hospital have risk factors
increased risk of VTE. In one study performed in for venous thrombosis such as immobility, infec-
the Netherlands, the incidence of VTE was noted tion, cancer and surgery. Compared with popu-
to be eight per 100,000 annually.37 Pregnancy, lations in the community, hospitalized patients
however, is associated with a higher risk of VTE have a more than 100-fold increase in the incidence
with a rate of 85 per 100,000.38 It is therefore vital of VTE.16 In addition, approximately half of all hos-
to consider the increased risk of VTE with oral con- pitalized patients are considered to be at risk of VTE
traceptives against that related to pregnancy. by conventional criteria.45 Among seven million
Studies have shown a 3 – 6-fold increase in risk of patients discharged from nearly 1000 American
VTE with third-generation combined oral contra- acute care hospitals, postoperative VTE was the
ceptives (COC) compared with a 2 – 3-fold increased second most common complication, the second
risk in those taking second-generation COCs.39,40 most common cause of excess length of stay and
This represents a 2 – 3-fold increased risk with third- the third most common cause of excess mortality
generation COC compared with the second gener- and cost. At least 50% of episodes of VTE in

4 Phlebology 2012;27 Suppl 2:2–11


P Wong and T Baglin. Epidemiology, risk factors and sequelae of VTE Review article

adults attributable to hospitalization are diagnosed mately 0.4%.2 The incidence of fatal PE in trauma
following discharge from hospital and presentation patients is high, accounting for 14% of deaths fol-
may occur up to three months after discharge.46 – 48 lowing hip fracture surgery.60
Up to 20% of patients admitted to a medical service Asymptomatic VTE has been reported in 15– 25%
and up to 40% admitted to a surgical service will of patients after vascular surgery if specific throm-
have thrombosis.22 However, an increasing pro- boprophylaxis is not used.61 Symptomatic VTE
portion of patients with hospital-acquired VTE are was noted in 0.9% of patients within 30 days after
medical patients.49,50 This is probably related to lower-limb bypass surgery or abdominal aortic
increasing use of thromboprophylaxis in surgical aneurysm (AAA) repair.62 The incidence of sympto-
patients over the last 30 years and a relative matic VTE within three months of major vascular
reduction of DVT in this population of patients. Fur- surgery ranges from 1.7% to 2.8% in a population-
thermore, postmortem studies indicate that the based study of 1.6 million surgical patients, with
majority of patients dying due to VTE acquired AAA repair or aorto-femoral bypass appearing to
during hospitalization are medical patients.3 – 5,11,12 have a higher risk of DVT than femoro-distal
It is therefore imperative that all patients admitted bypass.63 – 66 Even though varicose vein surgery
to hospital be risk assessed for VTE and prophy- has a low perceived risk of DVT, the incidence of
laxis commenced balancing the benefit against the DVT following varicose vein surgery has been
risk of bleeding. reported to be around 5.3%.67 These DVTs,
however, had minimal short- or long-term clinical
significance. The risk of DVT following major
Surgery
lower-limb amputation on the other hand is sub-
Immobility associated with surgery and general stantial, and can range up to 14.3%.64,68
anaesthesia carries a significant risk of VTE due to
the changes in all three elements of Virchow’s
Cancer
triad. Surgery induces damage to vessel walls and
a hypercoagulable state. Prolonged immobility The annual incidence of VTE in a population of
during the perioperative phase results in venous cancer patients is estimated at one in 200 and
stasis in the deep veins of the legs due to loss of cancer is associated with a 4.1-fold increased risk
calf muscle pump activity. In addition, general of thrombosis.6,69 Substances within the tumour
anaesthesia decreases vascular tone and distends cells such as proteases and tissue factor have pro-
veins resulting in more venous endothelial coagulant effects and the interaction between the
damage. The risk of VTE varies with the types tumour cells and macrophages lead to the acti-
and duration of surgery and patient characteristics. vation of platelet and coagulation network. Che-
The risk of VTE without thromboprophylaxis in motherapy is associated with a 6.5-fold increased
patients undergoing general surgical procedures risk of thrombosis, and this is thought to be due
varies between 15% and 30%, while the rates of to vascular damage and release of tumour necrosis
fatal PE range between 0.2% and 0.9%.51,52 Most factor and interleukins.6,70 Cancers involving the
day case surgery patients such as hernia repairs bone, ovary, brain, pancreas and lymphomas are
have a low risk of VTE.53 associated with the highest incidence of thrombosis
The risk of VTE appears to be lower following within six months of cancer diagnosis: 37.2, 32.6,
spinal or epidural anaesthesia.54 Coronary artery 32.1, 22.7 and 17– 20 per 1000, respectively.22
bypass surgery, major urological surgery, surgery Cancers of the ovary, pancreas, lung, stomach and
for gynaecological malignancies and major ortho- haematological malignancies have a high incidence
paedics surgery are all associated with a high risk of VTE in the year before the cancer diagnosis,
of VTE.55 – 57 Orthopaedic surgery and trauma are suggesting the possible role of occult cancer in
associated with multiple pro-thrombotic processes. causing thrombosis or a commonality of risk
Bone and muscle injury causes extensive endo- factors for both diseases.71
thelial damage and thrombin generation. Further-
more, patients are exposed to vasodilatory
Thrombophilia
anaesthetic agents, vessel trauma from the pro-
cedure and perioperative immobility.58 Asympto- Thrombophilic disorders can be classified into
matic DVT is common after major orthopaedic severe and mild. Severe thrombophilia disorders
surgery, which includes total hip, knee replacement include deficiencies of the endogenous anticoagu-
or hip fracture surgery.59 The rate of fatality from PE lants – antithrombin, protein C and protein S.
following hip and knee replacement is approxi- They are less common but may be more potent

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Review article P Wong and T Baglin. Epidemiology, risk factors and sequelae of VTE

risk factors for thrombosis.22 Mild thrombophilia recurrence.83 Increased D-dimer levels following
disorders include factor V Leiden, F2G20210A the completion of anticoagulant therapy after DVT
variant and possibly elevation of pro-coagulant is associated with residual venous thrombosis.84,85
factors such as factor VIII, von Willebrand factor, Both elevated D-dimer and residual venous throm-
and factors V, VII, IX and XI. bosis are associated with an increased risk of recur-
A high D-dimer is also a risk factor for first VTE rent DVT, with the former factor being more
in healthy individuals.72,73 The relative risk of pronounced.84
thrombosis with D-dimer in the top quarter of the Up to 85% of patients with acute symptomatic PE
normal population distribution was increased 2.5 – still have partial occlusion of the pulmonary circu-
3-fold, and the risk was even higher for idiopathic lation one week after thrombolysis or anticoagula-
thrombosis.73 While there is a causal association tion. More than 50% of patients have persistent
between heritable thrombophilia and venous scan defects at six months and complete resolution
thrombosis a strong gene – environment and gene – does not occur in the majority of patients by one
gene interaction precludes clinical utility of testing year.86 This therefore poses a diagnostic dilemma
for individual thrombophilia.74 Consequently, subsequently in patients who present later on and
indiscriminate testing for heritable thrombophilias who did not have a follow-up scan at the end of
in unselected patients presenting with venous the initial treatment.
thrombosis is not indicated.75
Mortality
Travel The case fatality rate of DVT, mainly due to fatal
PE, ranges from 1% in young patients to 10% in
All modes of travelling predispose to VTE and the
older patients, and is highest in those with under-
duration of travel is a main factor. Air, car, train or
lying malignancies.7,8,14 A population-based study
bus travel lasting for four hours or more can all
showed that the 30-day mortality rate after a first
increase the risk by about two-fold for several
venous thrombosis was 6.4% with a one-year mor-
weeks after the journey.76 Naturally, the risk of
tality of 21.6%.19 The high mortality rate in VTE is
VTE is increased in the presence of other pre-
principally determined by its relationship with
existing risk factors for VTE. Data on absolute rate
malignancy. However, even after exclusion of
of thrombosis with air travel suggest a rate of 1.5
patients with malignancies, the risk of mortality
per million for severe PE among those travelling
from VTE remained at 3.6% after one month and
more than 3000 miles and 0.39 per million for all
12.6% after one year.19 Up to 45% of deaths were
PE.77,78
directly attributable to PE. The one-year mortality
rate is similar for both DVT and PE, indicating an
effect of underlying disease, while the 30-day mor-
Sequelae
tality is twice as high in PE compared with DVT
DVT may lead to persistent chronic disease, which (10% versus 5%) indicating an effect of the thrombo-
can be severely disabling due to impaired venous sis itself. A majority of deaths (.90%) due to PE
return in the lower limbs, termed as post- occur in untreated patients in whom the diagnosis
thrombotic syndrome (PTS). PTS can occur in up is not made in life. Patients with symptomatic PE
to 20– 50% of patients.79 – 81 PE on the other hand in the RIETE registry were five time more likely to
may lead to chronic thromboembolic pulmonary die of fatal PE than patients with symptomatic
hypertension (CTPH). The other major outcomes DVT, and patients with massive PE were 17 times
of venous thrombosis are death, recurrence and more likely.87
major bleeding due to anticoagulation. The mortality rate for PE has been estimated to be
Recanalization occurs slowly after the develop- as high as 30% in studies that included autopsy-
ment of DVT. Residual venous thrombosis is based PE diagnosis, highlighting the fact again
present in up to 40% of patients without cancer at that many PE are not recognized clinically prior to
12 months and 25% at 36 months.82 Due to the fre- death.88 Mortality rates are lower among patients
quent incomplete clot resolution, the diagnosis of with idiopathic VTE and highest among those
recurrent ipsilateral DVT is often fraught with diffi- with malignancy-related VTE.
culty. One important tool in this regard is the The annual in-hospital fatality rate from VTE
demonstration that in patients with previous DVT could be as high as 12% and postmortem results
or PE and a suspected recurrence, a negative high- have shown that up to 10% of deaths in hospitals
sensitivity D-dimer assay result safely excludes are due to PE.3,4,14,49 The number of VTE-related

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P Wong and T Baglin. Epidemiology, risk factors and sequelae of VTE Review article

deaths in the EU was estimated at 543,454 per Recurrent DVT or PE is associated with a several-
annum.10 European epidemiological modelling fold increased likelihood of PTS and CTPH.
has shown that deaths from VTE could actually be However, recurrent VTE is only prevented for as
as high as more than 14 times those recognized as long as anticoagulation is continued.99 Decisions
being VTE-related, signifying a poor awareness regarding duration of anticoagulation should be
among clinicians of the potentially fatal outcome made with reference to whether or not a first
of VTE and the importance of providing at-risk episode of venous thrombosis was provoked or
patients with VTE prophylaxis.10 not, other risk factors and risk of anticoagulant
Deaths due to PE result from an acute fall in therapy-related bleeding.
cardiac output resulting in hypotension. Up to 5%
of patients have massive PE with hypotension at
presentation.87,89 Right ventricular dysfunction is Post-thrombotic syndrome
present in up to 40% of patients with acute PE PTS presents with symptoms of swelling, pain and
and normal blood pressure and fatal PE is twice chronic skin changes ranging from dryness to dis-
as likely in those with right ventricular dysfunc- colouration and venous ulcers. PTS can become
tion.89 – 91 In patients without pre-existing cardiac established after two years following acute DVT.
or pulmonary disease, the haemodynamic disturb- Several studies suggested proximal DVT is associ-
ance correlates with the extent of obstruction of ated with a higher risk of PTS compared with calf
the pulmonary circulation.92 DVT.100,101 The risk is further increased by recurrent
Patients with massive PE, defined as PE with ipsilateral DVT.100 Patients with DVT with subopti-
hypotension, do derive mortality benefit from mal international normalized ratio (,2.0) for more
thrombolysis.93 The haemodynamic benefit from than 50% of the time were noted to be twice as
thrombolysis, when compared with heparin, likely to develop PTS.102 Anticoagulant therapy
however, dissipates after the first few days.94 for 12 months as compared with six months does
not change the risk of PTS.101 This suggested that
early adequate treatment of DVT rather than the
Recurrence duration of treatment influences the development
of PTS and that thrombin generation may contrib-
VTE is often a chronic condition with recurrence ute to ongoing valvular damage immediately after
rates up to 5 – 7% annually after the first event and DVT.99 Graduated elastic compression stockings
patients are up to 40 times more likely to suffer a have been proven effective in preventing PTS in
further event compared with previously unaffected those with DVT.79,103
individuals.9,80,95,96 The risk of recurrence is highest
among those whose initial episode was associated
with malignancy and lowest among those whose Chronic thromboembolic pulmonary
initial episode was associated with a temporary
hypertension
risk factor such as surgery.9,80,95 Other risk factors
for recurrent thrombosis include PE as the first CTPH is defined as mean pulmonary artery
thrombosis event and proximal versus distal limb pressure greater than 25 mmHg that persists six
DVT.22 Residual vein obstruction (RVO) at the months after PE is diagnosed. It is characterized
time of stopping oral anticoagulant therapy follow- by intraluminal thrombus organization and
ing a first unprovoked episode was not associated fibrous stenosis or complete obliteration of
with an increased risk of recurrent VTE.97 In a pulmonary arteries. The consequence of CTPH is
recent meta-analysis, RVO was associated with a an increase in pulmonary vascular resistance result-
modestly increased risk of recurrent VTE in patients ing in pulmonary hypertension, progressive right
with DVT (unprovoked and provoked). However, heart failure and death. Less than 5% of patients
RVO did not seem to be a predictor of recurrent with persistent occlusion of the pulmonary circula-
VTE in patients with unprovoked DVT following tion after six months will develop CTPH. The inci-
anticoagulation discontinuation.98 An abnormal dence of CTPH ranges between 0.8% and 3.8%
D-dimer at one month following cessation of antic- after a first episode of PE.104,105 Risk factors for
oagulant therapy on the other hand was found to be CTPH include recurrent PE and previous multiple
an independent risk factor for recurrent VTE, while PE.105 On the other hand, up to two-thirds of
RVO with or without abnormal D-dimer following patients with CTPH have no history of previous
withdrawal of anticoagulant therapy did not acute PE.106 This may be due to pre-existing
influence the risk of recurrence. CTPH as a result of previous asymptomatic PE.99

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Review article P Wong and T Baglin. Epidemiology, risk factors and sequelae of VTE

The patients often present with either of two scen- 2 House of Commons Health Committee. The Prevention
arios: progressive dyspnoea on exertion, haemopty- of Venous Thromboembolism in Hospitalized Patients.
London: The Stationery Office, 2005
sis and/or signs of right heart dysfunction
3 Sandler DA, Martin JF. Autopsy proven pulmonary
including fatigue, palpitations, syncope or oedema embolism in hospital patients: are we detecting
after a single episode, or recurrent episodes of enough deep vein thrombosis? J R Soc Med 1989;82:
overt PE.106 Echocardiography is widely used as 203 –5
the initial diagnostic tool when CTPH is sus- 4 Lindblad B, Sternby NH, Bergqvist D. Incidence of
pected.107 Ventilation perfusion scintigraphy plays venous thromboembolism verified by necropsy over
30 years. BMJ 1991;302:709– 11
a pivotal role in determining whether pulmonary
5 Stein PD, Henry JW. Prevalence of acute pulmonary
hypertension is due to thromboembolism and embolism among patients in a general hospital and at
chest computed tomographic angiography remains autopsy. Chest 1995;108:978– 81
the preferred initial investigation. Pulmonary 6 Heit JA, Silverstein MD, Mohr DN, Petterson TM,
angiography is often reserved for characterizing O’Fallon WM, Melton LJ III. Risk factors for deep
the pulmonary vasculature in planning surgical vein thrombosis and pulmonary embolism: a
intervention.108 Patients with CTPH are treated population-based case-control study. Arch Intern Med
2000;160:809– 15
with lifelong anticoagulation to prevent recurrent 7 Nordström M, Lindblad B, Bergqvist D, Kjellström T. A
thrombotic events. Pulmonary thromboendarterect- prospective study of the incidence of deep-vein throm-
omy is the only potentially curative therapy for bosis within a defined urban population. J Intern Med
CTPH.109 1992;232:155– 60
8 Oger E. Incidence of venous thromboembolism: a
community-based study in Western France. EPI-GETBP
Study Group. Groupe d’Etude de la Thrombose de Bre-
Conclusion tagne Occidentale. Thromb Haemost 2000;83:657– 60
9 Cushman M, Tsai AW, White RH, et al. Deep vein
All individuals are at varying risk of VTE. In order thrombosis and pulmonary embolism in two cohorts:
to prevent VTE, it is vital to understand the risk that the longitudinal investigation of thromboembolism
individuals are exposed to, for example, prolonged etiology. Am J Med 2004;117:19 – 25
10 Cohen AT, Agnelli G, Anderson FA, et al. VTE Impact
air travel, in-hospital stay or types of surgery and Assessment Group in Europe (VITAE). Venous throm-
their own inherent risk (for example, predisposing boembolism (VTE) in Europe. The number of VTE
inherited or acquired medical conditions such as events and associated morbidity and mortality.
thrombophilia). Thromb Haemost 2007;98:756– 64
VTE is, and will remain, a major national health 11 Alikhan R, Peters F, Wilmott R, Cohen AT. Fatal pul-
problem, especially among the elderly. The inci- monary embolism in hospitalized patients: a necropsy
review. J Clin Pathol 2004;57:1254– 7
dence of VTE increases markedly with advancing 12 Baglin TP, White K, Charles A. Fatal pulmonary embo-
age. As the world population ages, the absolute lism in hospitalized medical patients. J Clin Pathol 1997;
number of events of VTE will likely increase. A 50:609– 10
large proportion of these events will manifest as 13 White RH. The epidemiology of venous thromboembo-
PE with its associated poor survival rates. On the lism. Circulation 2003;107:I4 – 8
other hand, the long-term sequelae of VTE, 14 Anderson FA Jr, Wheeler HB, Goldberg RJ, et al. A
population-based perspective of the hospital incidence
namely PTS and CTPH, will continue to add onto
and case-fatality rates of deep vein thrombosis and pul-
the extra financial burden to health-care costs. A monary embolism. The Worcester DVT Study. Arch
good understanding of the epidemiology and risk Intern Med 1991;151:933 – 8
factors of VTE will enable the treating medical prac- 15 Silverstein MD, Heit JA, Mohr DN, Petterson TM,
titioners to identify patients at risk and administer O’Fallon WM, Melton LJ III. Trends in the incidence
appropriate VTE prophylaxis to prevent the long- of deep vein thrombosis and pulmonary embolism: a
25-year population-based study. Arch Intern Med 1998;
term consequences of VTE.
158:585– 93
Conflicts of interest: None declared. 16 Heit JA, Melton LJ III, Lohse CM, et al. Incidence of
venous thromboembolism in hospitalized patients vs.
community residents. Mayo Clin Proc 2001;76:1102 – 10
17 Heit J, Cohen A, Anderson FJ. Estimated annual
number of incident and recurrent, non-fatal and fatal
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