Anda di halaman 1dari 55


Deep venous thrombosis (DVT)
clottingof blood in a deep vein of an
extremity (usually calf or thigh) or the
DVT is the primary cause of pulmonary
embolism. DVT results from conditions
that impair venous return, lead to
endothelial injury or dysfunction, or
cause hypercoagulability.

Stasis of blood
Vessel damage
Increased blood coagulability

Vessel trauma stimulates the clotting cascade.

Platelets aggregate at the site particularly
when venous stasis present
Platelets and fibrin form the initial clot
RBC are trapped in the fibrin meshwork
The thrombus propagates in the direction of the
blood flow
Inflammation is triggered, causing tenderness,
swelling, and erythema
Pieces of thrombus may break loose and travel
through circulation- emboli
Fibroblasts eventually invade the thrombus, scarring
vein wall and destroying valves.
Although the patency may be restored valve damage
is permanent, affecting directional flow
Clinical Manifestations
Tenderness in the calf (this is one of the
most important signs)
Swelling of the leg
Increased warmth of the leg
Redness in the leg
Bluish skin discoloration
Discomfort when the foot is pulled
Phlegmasia cerulea dolens
Originates as a platelet nidus in the
region of venous valves located in the
veins of the lower extremities.
Further growth occurs by accretion of
platelets and fibrin and progression to
red fibrin thrombus, which may either
break off and embolize or result in total
occlusion of the vein.
Pulmonary Emboli
From the thrombi originating in the
deep venous system of the lower
Rarely, they may originate in the
pelvic, renal, or upper extremity veins
and the right heart chambers.
Large thrombi lodge at the bifurcation
of the main pulmonary artery or the
lobar branches, accumulate and may
cause haemodynamic compromise.
Pulmonary Emboli
Smaller thrombi continue
distally, occluding smaller
vessels in the lung periphery.
These are more likely to produce
pleuritic chest pain by initiating
an inflammatory response
adjacent to the parietal pleura.
Most pulmonary emboli are
Risk Factors
Previous or current DVT
Surgery within the last 3 months
Central venous instrumentation within the last 3 months
Autoimmune diseases
Air travel *
In Women
Obesity (BMI 29)
Heavy cigarette smoking (>25 cigarettes per day)

Most Common Symptoms Most Common Signs

Dyspnea at rest or with Tachypnea (54 %)
exertion (73 %)
Tachycardia (24 %)
Pleuritic pain (44 %)
Cough (34 %) Rales (18 %),
>2-pillow orthopnea (28 %) Decreased breath sounds
Calf or thigh pain (44 %) (17 %),
Calf or thigh swelling (41 Accentuated pulmonic
Wheezing (21 %)
component of the second
heart sound (15 %)
Rapid onset of dyspnea
within seconds (46 %) Jugular venous distension
within minutes (26 %) (14 %)
Homans sign
Passive dorsiflexion of the foot with the
knee straight may give pain in the calf and
back of the knee when there is a deep
venous thrombosis.
Some concern that vigorous dorsiflexion

of the foot can expel clot from the veins

and so this test may have its dangers.
The sign is not specific for DVT
Clinical Decision Rules
Models for assessing clinical
Probability of Pulmonary Embolism
Wells Criteria
Geneva Score
Wells Score

Clinical symptoms of DVT

Traditional clinical probability
(leg swelling, pain with 3.0
assessment (Wells criteria)
Other diagnosis less likely High >6.0
than pulmonary embolism
Moderate 2.0 to 6.0
Heart rate >100 1.5
Low <2.0
Immobilization (3 days) or
surgery in the previous four 1.5
Simplified clinical probability
assessment (Modified Wells criteria)
Previous DVT/PE 1.5
PE likely >4.0
Hemoptysis 1.0
Malignancy 1.0 PE unlikely 4.0
Simplified Geneva Score

Variable Score
Age >65 1
Previous DVT or PE 1
Surgery or fracture within 1 month 1
Active malignancy 1
Unilateral lower limb pain 1
Hemoptysis 1
Pain on deep vein palpation of
lower limb and unilateral edema
Heart rate 75 to 94 bpm 1
Heart rate greater than 94 bpm +1
Score of less than 2 is low probablility for PE, score of less than 2 plus a
negative D-dimer results in a likelihood of PE of 3%
Diagnostic Algorithm
Algorithm for Diagnosis of Pulmonary Embolism
Clinical sign & symptoms
of PE
Wells Score
Start heparin if >6, Perform D-dimer
PE less likely PE likely

D-dimer CTPA
R/w clinical probability & D dimer Diagnosis of
results PE

VTE Treatment
PE less likely & PE likely & - PE likely algorithm
+ D dimer D dimer with + D
results results dimer results

Perform Ultrasou
Risk of PE is low.
duplex nd
Consider other
ultrasound of results?
the leg
Venous Thromboembolism Treatment Algorithm

Diagnosis of DVT/PE
Complicated thromboembolism of


OP treatment appropriate? protocol
Inpatient education

Other Complication
Therapies during therapies
Cnt. Anticoagulation with Failure?
followup & secondary
Usually shows hypoxia, hypocapnia, respiratory
A-a gradient:
Normal 7-14 depending on age
Increases with age, FiO2 and supine posture
Estimate of normal for age:
Age/4 +4
A-a gradient = (FiO2 x713 pCO2/0.8) PaO2
If A-a gradient normal, PaO2 <80, Pa CO2 >45
then hypoventilation accounts for hypoxia
Increased A-a gradient occurs in V/Q
mismatch, shunting and any kind of barrier to
diffusion (e.g. pulmonary edema)
BUT can be normal and still have PE!
It specific degradation product of cross-linked fibrin.

Because concurrent production and breakdown of clot

characterize thrombosis, patients with thromboembolic
disease have elevated levels of D-dimer.

Three major approaches for measuring D-dimer

latex agglutination
blood agglutination test
fibrinolysis of
factor XIIIa
fibrin into an
array of
forms. The D-
dimer and E
are the result
of terminal
ECG in Pulmonary Embolism
Most commonly sinus
tachycardia, with possible
nonspecific ST/T wave
Only 10% of patients can
have the S1Q3T3 so not
Other EKG abnormalities
including atrial arrhythmias,
right bundle branch block,
inferior Q-waves, and
precordial T-wave inversion
and ST-segment changes, are
associated with a poor
Chest Radiography
Not a sensitive or specific test for the
diagnosis of PE.
Atelectasis, Pleural effusion, or a
pulmonary parenchymal abnormality is
noted most commonly
Only a small portion of patients with PE
have a normal CXR.
Radiographic Signs Westermark Sign
Radiographic Signs Hamptons Hump
Useful if Normal (negative predictive value of
Also useful if High probability (positive predictive
value of 85 to 90%)
Unfortunately, only diagnostic in 30 to 50% of
CT Angiography

Studies have shown sensitivity of close to

95% with an experienced observer
One of the most commonly cited benefits of
CTA is its ability to detect alternative
pulmonary abnormalities that may explain
the patient's symptoms and signs
In 67% of patients without PE, CT provided
additional information for alternate diagnosis
May predispose patients to further
unnecessary testing
CT Agiogram
Pulmonary Angiography
Pulmonary Angiography in
The gold standard
A negative pulmonary angiogram excludes
clinically relevant PE.
The risk of embolization in patients with a
negative angiogram is extremely low
More than 80% of pts with PE will have
abnormalities of RV size or function, or TR.
McConnells sign regional wall motion
abnormalities that spare the R ventricular apex
are very suggestive of PE
BUT echo is only really used for Dx of massive
lifethreatening PEs when rapid diagnosis is
needed to determine whether thrombolysis
should be given.
Management of DVT

These include lifestyle changes like
Avoid smoking
Eating a healthy balanced diet
Getting regular exercise and
Maintaining ahealthy weight or losing weight if patient
Leg Raising:This reduces the pressure in the calf veins

Anticoagulation is the foundation for successful treatment

of DVT and PE
Immediately effective anticoagulation is initiated with a
parenteral drug: unfractionated heparin (UFH), low-
molecular-weight heparin (LMWH), or fondaparinux.
Parenteral agents are continued as a transition or "bridge"
to stable, long-term anticoagulation with Warfarin.Since it
requires 57 days to achieve a therapeutic effect. During
that period, one should overlap the parenteral and oral
However, anticoagulants do not directly dissolve thrombus
that already exists.
Unfractionated Heparin

MOA is by binding to and accelerating the activity of

antithrombin, thus preventing additional thrombus
formation and permitting endogenous fibrinolytic
mechanisms to lyse clot that already has formed.
UFH is dosed to achieve a target activated partial
thromboplastin time (aPTT) that is 23 times the upper limit
of the laboratory normal.
For UFH, a typical intravenous bolus is 500010,000 units
followed by a continuous infusion of 10001500 U/h

The major advantage of Major disadvantage of

UFH is its short half-life. UFH is that achieving the
This is especially useful if target aPTT is empirical
the patient may undergo and may require repeated
an invasive procedure blood sampling and
such as embolectomy heparin dose adjustment
every 46 hours.
Furthermore, patients are
at risk of developing

Low-Molecular-Weight Heparins

These fragments of UFH exhibit less binding to plasma proteins

and endothelial cells and consequently have greater
bioavailability, a more predictable dose response, and a longer
half-life than does UFH.
No monitoring or dose adjustment is needed unless the patient is
markedly obese or has chronic kidney disease.
2 commonly used LMWH preparations are enoxaparin and
Enoxaparin is approved as a bridge to warfarin for VTE.
Dalteparin is also approved as monotherapy without
warfarin for symptomatic VTE patients with cancer in a
dose of 200 U/kg once daily for 30 days, followed by 150
U/kg once daily for months 26.

Fondaparinux, an anti-Xa pentasaccharide, is administered as

a once-daily subcutaneous injection in a prefilled syringe to
treat DVT and PE as a "bridge" to warfarin.
No laboratory monitoring is required.
Patients weighing <50 kg receive 5 mg, patients weighing 50
100 kg receive 7.5 mg, and patients weighing >100 kg
receive 10 mg.
Fondaparinux is synthesized in a laboratory and, unlike LMWH
or UFH, is not derived from animal products
It does not cause heparin-induced thrombocytopenia.
The dose must be adjusted downward for patients with renal
dysfunction because the kidneys metabolize the drug.

This vitamin K antagonist prevents carboxylation activation

of coagulation factors II, VII, IX, and X.
The full effect of warfarin requires at least 5 days even if
the prothrombin time, used for monitoring, becomes
elevated more rapidly.
If warfarin is initiated as monotherapy during an acute
thrombotic illness, a paradoxical exacerbation of
hypercoagulability can increase the likelihood of
thrombosis rather than prevent it.
Overlapping UFH, LMWH, or fondaparinux with warfarin for
at least 5 days can counteract the early procoagulant effect
of unopposed warfarin.
Warfarin Dosing
In an average-size adult, warfarin usually is initiated in a dose of 5 mg.
Doses of 7.5 or 10 mg can be used in obese or large-framed young
patients who are otherwise healthy.
Patients who are malnourished or who have received prolonged
courses of antibiotics are probably deficient in vitamin K and should
receive smaller initial doses of warfarin, such as 2.5 mg.
The Prothrombin time is standardized by calculating the International
normalized ratio (INR), which assesses the anticoagulant effect of
warfarin (Chap. 58). The target INR is usually 2.5, with a range of 2.0
The warfarin dose is titrated to achieve the target INR.
Proper dosing is difficult because hundreds of drug-drug and drug-food
interactions affect warfarin metabolism.
Variables such as increasing age and comorbidities such as systemic
illness reduce the required warfarin dose
Novel Anticoagulants

Novel oral anticoagulants are administered in a fixed dose,

establish effective anticoagulation within hours of
administration, require no laboratory coagulation
monitoring, and have few of the drug-drug or drug-food
interactions that make warfarin so difficult to dose.
Rivaroxaban, a factor Xa inhibitor, and Dabigatran, a
direct thrombin inhibitor, are approved in Canada and
Europe for prevention of VTE after total hip and total knee
Because of these drugs' rapid onset of action and
relatively short half-life compared with warfarin, "bridging"
with a parenteral anticoagulant is not required.
Complications of Anticoagulants
The most serious adverse effect of anticoagulation is hemorrhage. For life-
threatening or intracranial hemorrhage due to heparin or LMWH, protamine sulfate
can be administered.
Major bleeding from warfarin is best managed with prothrombin complex
concentrate. With non-life threatening bleeding in a patient who can tolerate large
volume, fresh-frozen plasma can be used. For minor bleeding or to manage an
excessively high INR in the absence of bleeding, oral vitamin K may be
Heparin-induced thrombocytopenia (HIT) and osteopenia are far less common with
LMWH than with UFH. Thrombosis due to HIT should be managed with a direct
thrombin inhibitor: Argatroban for patients with renal insufficiency and Lepirudin
for patients with hepatic failure. In the setting of percutaneous coronary
intervention, one should administer bivalirudin.
During pregnancy, warfarin should be avoided if possible because of warfarin
embryopathy, which is most common with exposure during the sixth through
twelfth week of gestation. However, women can take warfarin postpartum and
breast-feed safely. Warfarin can also be administered safely during the second
Various inferior vena
caval filters
Inferior Vena Caval Filters

The two principal indications for insertion of an IVC filter

(1) Active bleeding that precludes anticoagulation
(2) Recurrent venous thrombosis despite intensive
It is not useful in PE as the filter itself may fail by
permitting the passage of small- to medium-size clots.
Large thrombi may embolize to the pulmonary arteries via
collateral veins that develop.
Paradoxically, by providing a nidus for clot formation, filters
double the DVT rate over the ensuing 2 years after

Successful fibrinolytic therapy rapidly reverses right heart failure and may
result in a lower rate of death and recurrent PE by
(1) dissolving much of the anatomically obstructing pulmonary arterial
(2) preventing the continued release of serotonin and other neurohumoral
factors that exacerbate pulmonary hypertension
(3) lysing much of the source of the thrombus in the pelvic or deep leg
veins, thereby decreasing the likelihood of recurrent PE.
The preferred fibrinolytic regimen is 100 mg of recombinant tissue
plasminogen activator (tPA) administered as a continuous peripheral
intravenous infusion over 2 hours. Patients appear to respond to
fibrinolysis for up to 14 days after the PE has occurred.
Contraindications to fibrinolysis include intracranial disease, recent
surgery, and trauma. The overall major bleeding rate is about 10%,
including a 13% risk of intracranial hemorrhage.
The only FDA-approved indication for PE fibrinolysis is massive PE
Surgical Options

Pulmonary Embolectomy :
The risk of intracranial hemorrhage with fibrinolysis has prompted a
renaissance of surgical embolectomy. More prompt referral before the onset of
irreversible cardiogenic shock and multisystem organ failure and improved
surgical technique have resulted in a high survival rate. A possible alternative
to open surgical embolectomy is catheter embolectomy. P
Pulmonary Thromboendarterectomy :
Chronic thromboembolic pulmonary hypertension occurs in 24% of acute PE
patients. Therefore, PE patients who have initial pulmonary hypertension
(usually diagnosed with Doppler echocardiography) should be followed up at
about 6 weeks with a repeat echocardiogram to determine whether pulmonary
arterial pressure has normalized. Patients impaired by dyspnea due to chronic
thromboembolic pulmonary hypertension should be considered for pulmonary
thromboendarterectomy, which, if successful, can markedly reduce, and at
times even cure, pulmonary hypertension. The operation requires median
sternotomy, cardiopulmonary bypass, deep hypothermia, and periods of
hypothermic circulatory arrest. The mortality rate at experienced centers is
approximately 5%.
Methods of DVT Prophylaxis
Graduated compression stockings
Intermittent pneumatic compression
Unfractionated heparin 5000 s.c TDS
Low-molecular weight heparins
Enoxaparin(0.4cc), Dalteparin(5000 U daily)

Vitamin K antagonists
Warfarin, acenocoumarol, phenindione, & dicoumarol

Fondaparinux (Factor Xa inhibitor)

3-6 months in most patients
Indefinite treatment:
>1 spontaneous event
One spontaneous life threatening event
Antiphospholipid syndrome
Antithrombin deficiency
>1 genetic allelic abnormality
Homozygote for Factor V Leiden or prothrombin gene
Heterozygote for both
Protein C/S deficiency
Continuing RF especially active advanced CA
Summary and Recommendations
Consider your patients risk factors for
pulmonary embolism
The clinical presentation of acute pulmonary
embolism is variable and nonspecific
The major diagnostic tests employed in the
evaluation of a patient with suspected PE
include d-dimer testing, CTPA, V/Q scanning,
venous ultrasonography, and conventional
pulmonary angiography
Follow a diagnostic algorithm that combines
CTPA, d-dimer and clinical assessment