Venous Thromboembolism

Fozia A. (Hematology fellow)

May, 2020
 Venous Thromboembolism
Outlines
• Definition
• Pathogenesis
• Risk Factors
• Approach to patients
• Management
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Venous Thromboembolism

• is a clinical spectrum which encompasses superfical

thrombophlebitis,deep vein thrombosis & pulmonary embolism.
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Epidemiology

• Annual incidence is 0.1%.

• 2-5% of the population is affected during life time.
• the 3rd most common cause of CV death in the western society.
• Over all incidence is decreasing because of increasing adoption of
effective VTE prevention strategies.
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Pathogenesis

• Virchow's triad remains the base for understanding the pathogenesis of

venous thrombosis.
• Prothrombogenic stimuli;
I) Venous stasis-could result from;
-immobility
-obstruction
-raised venous pressure
-venous dilation
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• Venous stasis will increase viscosity, promote formation of
microthrombi and, also increase endothelial damage because of
the venous dilation it causes.

II) Endothelial damage

• will expose the thrombogenic sub endothelial surface (tissue
factor) to procoagulants in the blood.
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• III) Activation of coagulation/Hypercoagulability
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• Antithrombotic mechanisms

• Inhibitors; (e.g. Antithrombin III, activated protein C and

activated protein S)
• Hepatic clearance of activated coagulation factors and soluble
fibrin polymer complexes.
• The fibrinolytic System.
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• Therefore, any imbalance in the equilibrium between the
prothrombotic and antithrombotic mechanisms will result in
coagulation at inappropriate time, location and in an excessive
manner.
• In addition, the thrombi can breaks off from its location of origin
and travel to the right heart & in to the pulmonary artery
resulting in pulmonary embolism.
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Risk Factors
• can be identified in >80% of patients with VTE.
• usually more than one factor is identified in patient.
• can be; Inherited risk factors and,
Acquired risk factors
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1. Inherited (Primary) Thrombophilc Disorders
• should be suspected in a patient with the following
characteristics;
-young age(<45 years)
-positive family history
-history of recurrent thrombosis
-thrombosis at unusual anatomic location (like CVT, splanchnic
venous circulation thrombosis…..)
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• includes-Factor V Leiden mutation (Activated protein C
resistance)
-Prothrombin gene mutation,
-ATIII, PC or PS deficiency ,
-Hyperhomocysteinemia,
-Dysfibrogenemia
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2. Acquired (Secondary) hypercoagulable
states
• Age (>40yrs)
• Malignancy
• Surgery & Trauma-orthopedic, neurosurgery, major abdominal
surgery being the highest risk.
• Previous VTE history-the single most important risk factor
• Myeloproliferative neoplasms-especially for splanchnic
circulation thrombosis.
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• Pregnancy
• Estrogen use (OCP,HRT)
• Family history
• Prolonged bed rest ≥3 days
• Prolonged air travel (>4 hrs.)
• Antiphospholipid antibody syndrome
• Obesity, Dyslipidemia
• DM, CHF
• Nephrotic syndrome…
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Approach to a patient
History
• Leg pain; occurs in 50% of patients but is entirely non specific.
doesn’t correlate with size location or extent of
thrombus.
• Swelling; the most specific symptom of DVT & is usually
unilateral.
could be bilateral if thrombus is at iliac bifurcation of
pelvic veins or the IVC.
• history to asses presence of risk factors.
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Physical examination
• Tenderness-occurs in 75% of patients.
• Homan’s sign-calf pain on passive dorsiflexion of the foot is
unreliable for the presence of DVT and is not recommended
nowadays.
• Phlegmasia cerulea dolens-markedly edematous, painful and
cyanotic leg 20 to massive
ileofemoral occlusion.
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Clinical Feature of PE
• Acute PE; patients develop symptoms & signs immediately after
obstruction of pulmonary vessels.
• can be;
• Massive PE;-PE with acute onset hypotension.
-a catastrophic entity that frequently results in
acute right ventricular failure and death usually in
1-2 hrs if not treated immediately.
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• Sub massive PE;-all acute PE not meeting the definition of
massive PE.
-sudden onset unexplained SOB & tachypnea.
-cough, hemoptysis or chest pain.
-fever, S3 gallop, accentuated P2
-± symptoms & signs of DVT.

• Chronic PE; patients develop slowly progressive dyspnea over

a period of years due to pulmonary hypertension.
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• since signs & symptoms of VTE lack both specificity & sensitivity,
pre test risk stratification is very important.
• while other pretest probability scoring systems are available, the
Well’s score appears to be most commonly used.
• All diagnostic workups should be preceded by pre test risk
stratification and diagnostic workups should be guided by the
pretest.
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Diagnostic Workup
DVT
• Compression Ultrasound-is the diagnostic test of choice in
patients with suspected DVT.
• Sensitivity & specificity is >90%.
• it is most useful when the results are combined with an
assessment of pretest probability.
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• Serum D-dimer level

• D-dimer, a degradation product of cross-linked fibrin, is elevated
in nearly all patients with acute DVT.
• However, specificity is low as it can be elevated in many other
conditions (e.g. malignancy, sepsis, recent surgery or trauma,
pregnancy, renal failure).
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Pulmonary thromboembolism
• CXR-normal in up to 1/3rd of patients.
• nonspecific abnormalities are common (e.g. atelectasis, effusion)
• is typically performed to look for an alternative cause of the
patient's symptoms (e.g. pneumonia).
• rare findings but, which should raise the suspicion of PE;
-Hampton's hump
-Westermark's sign
-Palla’s sign
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• Computed tomography pulmonary angiography (Chest CT

angiogram)
• the diagnostic imaging modality of choice for PTE because of its
high sensitivity & specificity.
• Pulmonary angiography
• The gold standard of test for PTE but not used routinely because
of the invasiveness of the procedure.
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• Ventilation perfusion (V/Q) scan
• mostly reserved for patients in whom CTPA is contraindicated or
inconclusive, or when additional testing is needed.
• Echocardiography-although not definitive, the diagnosis of PE is
supported on echo by the presence of new right heart strain (RV
dysfunction) ± tricuspid regurgitation.
• regional RV wall motion abnormality sparing the RV apex (i.e.
McConnell’s sign) or RV thrombus may rarely be seen.
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• ECG-abnormalities, although common in patients with suspected

PE, are nonspecific.
• Sinus tachycardia is the most common finding
• S1Q3T3 pattern is highly specific, but is found in <10% of patients
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• Screening for inherited thrombophilia

• shouldn’t be routine as management wont be changed in most
scenarios based on the result & its also not cost effective
• When to do;
-Age <45 years without immediate identifiable risk factors
-Family history
-Recurrent clots
-clot in an unusual site (splanchnic circulation (JAK2 status
should always be checked), cerebral)
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-unprovoked upper extremity clot (no catheter, no surgeries)

-patients with warfarin-induced skin necrosis (they may have
protein C deficiency)
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Management
Goals
• prevent death from PTE,
• prevent morbidity from recurrent venous thrombosis or
pulmonary embolism, and
• prevent or minimize the post-thrombotic syndrome (PTS).
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Anticoagulation
• first line of therapy for DVT & PE.
• Options;
-Unfractionated heparin (UFH)
-Low molecular weight heparin (LMWH)
-Warfarin
-Direct oral anticoagulants (Rivaroxaban, Apixaban,
Edoxaban, Dabigatran)
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• Warfarin shouldn't be used as the sole initial anticoagulant.

-can’t antagonize the already formed vitamin K dependent
factors, so action is delayed for the first ~5 days,
-may rather have thrombotic effect (antagonizes PC & PS
activity) for the first few days
• Warfarin should be overlapped with heparin for 05 days or till
therapeutic INR of 2-3 is achieved for two consecutive times.
• DOACs are nowadays getting more attention as they don’t need
laboratory monitoring of the coagulation panel & for their less
drug-drug interaction.
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• Duration of anticoagulation
• At least 03 months of anticoagulation therapy is recommended for
all venous thromboembolism.
• long term (extended) with VKA or DOACs is recommended for
unprovoked DVT.
• pregnancy associated VTE should be treated with anticoagulation
for the duration of the pregnancy and up to 6–12 weeks
postpartum, for a minimum 3 months in total.
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• Thrombolytics
• indicated in patients with massive PTE or for acute massive
proximal DVT (phlegmasia cerulea dolens).
• provides more rapid lysis of pulmonary emboli and more rapid
restoration of right ventricular function and pulmonary perfusion
than does anticoagulant treatment.
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• Inferior Vena Cava (IVC) Filter

• is indicated for patients with acute VTE and an absolute
contraindication to anticoagulant therapy and the rare patients
who have objectively documented recurrent VTE during
adequate anticoagulant therapy.
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Prophylaxis
Mechanical:
• Early ambulation
• Graded compression stocking
• Pneumatic compression boot
Pharmacological
• UFH: given every 8 hours SC
• LMWH: Enoxaparin 30-40mg SC every 24 hours
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• Fondaparinux: 2.5mg SC every 24 hours

• Rivaroxaban
Inferior vena cava (IVC) filter
• Considered as secondary prophylaxis or secondary prevention
against PE but not DVT.
• IVC filter is indicated in patients with high risk of recurrence
when other methods are contra-indicated.
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Thanks!!!