Venous Thromboembolic
Disease
Pathogenesis of Thrombosis
• Thrombosis is the pathological process by which a localized solid mass
of blood constituents (a blood clot or thrombus) forms within a blood
vessel, mostly as a result of fibrin formation with a variable
contribution from platelets and other cells.
• Venous thrombi are classically described as red thrombi reflecting the
more prominent contribution of fibrin and red blood cells in
comparison to the arterial, platelet rich (white thrombi)
• Thrombosis factors: (Virchow’s triad)
- Stasis*
- Hypercoagulable state*
- Endothelial damage
Definitions
• Deep venous thrombosis (DVT) usually starts in the pocket above the
vein valves of the lower limbs, then extends further
• If limited to vein at the level of the calf it is called (distal DVT)
• If it reaches the popliteal vein or above it is called (proximal DVT)
• In less than 10% of venous thromboses arise from other sites rather
than the lower limbs, such as upper limbs, cerebral venous sinuses
and the splanchnic veins. These are called unusual site thrombosis
• This thrombosis may embolise through the circulation to the
pulmonary artery and branches to form pulmonary embolism(PE)
Epidemiology and Risk Factors
• Common disease: 1 per 1000 per year
• Uncommon in childhood incidence increases with age
• 60% present with DVT, 40% present with PE
• Significant percentage of VTEs are subclinical
• Strong risk factors (risk 10–50-fold): major surgery, trauma and absolute
bed rest.
• Moderate risk factors (risk 3–10-fold): pregnancy, estrogen therapy
minor surgery under general anaesthesia and Most heritable
thrombophilia.
• Weak risk factors (risk up to 3-fold): obesity and long travel.
Clinical features
• DVT: unilateral leg pain and swelling, redness and warmth to touch
may be noted, occasionally dilated superficial veins and tenderness
over the course of the obstructed vein.
• PE: presentation varies according to the level and degree pulmonary
artery occlusion
- Peripheral (small) PE (65%):
Tachypnoea and tachycardia, pleuritic chest pain and breathlessness,
Sometimes with haemoptysis. Localized crackles and a pleural rub over
an area of pulmonary infarction may be heard on auscultation.
- Central (submassive) PE (25%):
breathlessness with central chest pain.
- Massive PE(10%):
syncope, hypotension, shock, with raised JVP and right ventricular
heave
Differential diagnosis
Differential diagnosis
Diagnosis
• Initial investigations **
- ECG: may be normal, the more common abnormality is sinus
tachycardia, occasionally right ventricular strain pattern can be seen
(inverted T waves in inferior and right pericardial leads), the classical
(S1Q3T3) is rarely seen
- Chest Xray:
may be normal, but can show unspecific abnormalities like, atelectasis,
pleural effusion, elevated hemidiaphragm.
Rare classical findings are Hampton hump, Westermark sign
• Initial investigations
- ABG’s: may be normal but can show hypoxia with hypocapnia
- Markers of cardiac injury: may be normal, but high BNP levels due to
right ventricular stretching, high troponin level if myocardial injury
occurs
All these initial investigations are not specific
• Risk scoring
- The two-level Well’s score for DVT, and the two-level Wells score for
PE are used to classify patients into two groups, likely or unlikely to
have DVT or PE
- The Well’s scores for DVT and PE do not confirm or exclude the
disease, but they are used to guide further assessment
• D-dimer:
- A fibrin degradation product: high levels indicate activation of the
coagulation system like infection, inflammation, postoperatively, in
cancer and during pregnancy.
- Sensitive for VTE but not specific (high negative predictive value)
• DVT imaging:
- Ultrasonography of the deep venous system: modality of choice
because it is quick and non invasive
- Venography: the gold standard, was historically used
• PE imaging:
- Computed tomographic pulmonary angiography (CTPA):
Modality of choice, available, sensitive, can provide alternative
diagnosis
- V/Q isotope scan:
Used when CTPA is contraindicated
Shows a mismatch in ventilation and perfusion scans (area of
ventilation with no perfusion)
- Pulmonary artery angiography: gold standard
Treatment
• Anticoagulation with either traditional anticoagulants or direct oral
anticoagulants
• Thrombolysis: in selected patients
• Surgical intervention
• Traditional anticoagulation:
- Low molecular weight heparin (LMWH) until sufficient coagulation
with warfarin in achieved
- Then keeping the patient anticoagulated -as judged by the
international normalized ratio (INR)
• Direct oral anticoagulants
- direct factor Xa inhibitors (apixaban, rivaroxaban and edoxaban)
- direct thrombin inhibitor (dabigatran)
- Pros: no need for monitoring, no drug/food interactions
Traditional
anticoagulation
_____________
(DOAC)
anticoagulation
• Thrombolysis
- Indicated in massive PE when systolic blood pressure <90 mmHg
- Controversial if moderate risk PE (signs right ventricular dysfunction
without hypotension)
• Surgical interventions
- Surgical embolectomy: if massive PE but thrombolysis in
contraindicated
- Inferior vena cava filter: if VTE patient has contraindication to
anticoagulation
• https://www.youtube.com/watch?v=JQ7aojMamSU
(embolectomy of massive PE that represented the femoral vein
anatomy )
• Duration of anticoagulation
- At least three months
- The decision of further anticoagulation after three months is taken
upon the risk of recurrent thrombosis vs the risk of bleeding
- Generally, patients with unprovoked VTE or have permanent
provoking factor should receive long term anticoagulation beyond
three months
- Patients with unprovoked or recurrent VTE should be considered for
thrombophilia evaluation
Acute complications
• Pulmonary embolism
• Paradoxical emboli (stroke, mesenteric ischemia)
• Phlegmasia alba dolens and Phlygmasia cerulea dolens :
total occlusion of veins and collaterals, resulting acute lower limb
ischemia (limb thretenening DVT)
Chronic complications
• Post-thrombotic syndrome
- Pain, swelling, heaviness, itching and skin discoloration of the affected
limb
- May develop venous ulceration later
• Pulmonary hypertension
- Should be suspected if breathlessness persists after treatment of PE
