Venous thromboembolism

Epidemiology

• 1/1000 individuals per year
  • 2/3 DVT, 1/3 PE
• 50% of PEs unprovoked

Risk Factors

• Demographic
  • Age
  • Sex
  • Race
  • BMI
• Provoking factors
  • Surgery/trauma
  • Acute medical illness
  • Immobility
  • Hormonal therapy and pregnancy
  • Cancer and chemotherapy
• Hereditary thrombophilias
• Biochemical/Acquired conditions
  • Antiphospholipid antibody syndrome
  • Elevated Factor VIII

Clinical Manifestations

History

• Assess if it was provoked by a transient risk factor:
  • Surgery, hospitalization, or plaster cast immobilization within the last 3 months
  • Central venous catheter-associated VTE
  • Estrogen therapy, pregnancy, flight over 8 hours, recent leg injury or immobilization within the past 6 weeks

Signs & Symptoms

• 3+ cm difference in calf circumference measured 10 cm below the tibial tuberosity
• Dilated non-varicose veins
• Tenderness over deep veins
• Homan's sign: flexing the ankle causes calf pain (poor sensitivity and specificity)
• Phlegmasia cerulea dolens

Well's Criteria for DVT (C3PO + R2D2)

• Cancer within 6 months
• Calf diameter increase >3 cm
• Collateral superficial veins (non-varicose)
• Pitting edema confined to symptomatic leg
• Oedema of the entire leg
• tenderness along deep venous system (t = + in mnemonic)
• Recently bedridden for > 3 days
• Recent immobilization of leg (cast, paralysis)
• DVT in the past
• Diagnosis other than DVT likely (2 points off)

Well's Criteria for PE

• Tachycardia (> 100 bpm) 1.5 points
• Hemoptysis 1 point
• Immobilization (< 4wks) 1.5 points
• Signs or symptoms of DVT 3 points
• Active malignancy (<6/12) 1 point
• Previous DVT or PE 1.5 points
• Etiology most likely PE 3 point

Investigations

• Generally don't screen for hereditary thrombophilias, as it does not change management
• No need to screen for occult malignancies (based on SOME trial 2013
• CBC, renal and liver function testing, chest X-ray
• Age-appropriate cancer screening

Management

• Anticoagulation
  • Acutely, can use unfractionated heparin infusions, if the patient may require interruption of therapy
  • Avoid long-term UFH, which is the only anticoagulant shown to have a higher risk of recurrence
• Outpatient treatment options:
  • Warfarin 10/5/5 then INRs
  • DOACs
    • Apixaban 10mg BID x7d then 5mg BID x3wk then 2.5 BID
    • Rivaroxaban 15mg BID x21days then 20mg OD
    • Dabigatran requires LMWH induction, for some reason
  • Low-molecular weight heparins preferred in malignancy (CLOT trial)
• Duration of treatment is 3 months if provoked or indefinitely if unprovoked
• For long-term prophylaxis, can consider ASA or rivaroxaban 10mg (EPCAT II trial)
• Thrombolysis of unclear benefit, but probably should be used if patient is unstable from PE
• IVC filter
  • If there is a contraindication to anticoagulation
  • Probably only necessary if acute clot
  • Retrievable up to a year

Prognosis

• High risk of recurrence for unprovoked VTE
• After first unprovoked episode, cumulative incidence for recurrence is 16% at 2 years, 25% at 5 years, and 36% at 10 years.
  • Men have a 1.4x higher risk
  • Positive D-dimer has 2x higher risk
  • Proximal DVT 5x higher than distal DVT
  • Proximal DVT 1.4x higher than PE alone, and DVT + PE is 1.5x higher than PE alone
• 4% case fatality with recurrent episode
• Provoked is about a third the risk of unprovoked
  • The stronger the provoking factor (i.e. major surgery), the lower the recurrence risk

Further Reading

• Longterm risk of symptomatic recurrent venous thromboembolism after discontinuation of anticoagulant treatment for first unprovoked venous thromboembolism event: systematic review and meta-analysis. BMJ. 2019;366.