Treatment and Prevention of Thrombotic Events in Antiphospholipid Syndrome
Statement C is TRUE: Arterial thrombosis in APS should be treated with vitamin K antagonist targeting INR 2.0-3.0 combined with aspirin 75-100 mg/day. 1, 2, 3, 4
Analysis of Each Statement
Statement A: Unprovoked Venous Thrombosis - Low-dose Aspirin 75-100 mg/day
This is FALSE. Aspirin monotherapy is insufficient for patients with confirmed APS and unprovoked venous thrombosis. 1
- Correct treatment: Adjusted-dose vitamin K antagonist (warfarin) with target INR 2.5 (range 2.0-3.0) is the gold standard for venous thrombosis in APS. 1, 2, 5
- Aspirin alone (75-100 mg daily) is only appropriate for asymptomatic patients with high-risk antiphospholipid antibody profiles who have NOT yet experienced thrombotic events (primary prevention). 2, 3
- Once unprovoked venous thrombosis occurs in APS, lifelong anticoagulation with warfarin is required, not aspirin monotherapy. 1, 5
Statement B: Arterial Thrombosis - VKA to Target INR 3.0-4.0
This is FALSE. High-intensity anticoagulation (INR 3.0-4.0) does not provide additional benefit over moderate-intensity therapy and increases bleeding risk. 1
- Two randomized controlled trials (Finazzi et al. and Khamashta et al.) demonstrated no superiority of high-intensity warfarin (INR 3.0-4.5) over moderate-intensity (INR 2.0-3.0) for preventing recurrent thrombosis in APS. 1
- The CHEST guidelines explicitly recommend AGAINST high-intensity warfarin, suggesting moderate-intensity INR 2.0-3.0 instead. 1
- Major bleeding risk is not reduced with high-intensity therapy, making the risk-benefit ratio unfavorable. 1
Statement C: Arterial Thrombosis - VKA to Target INR 2.0-3.0 with Aspirin 75-100 mg/day
This is TRUE. Combined therapy is the recommended approach for arterial thrombosis in APS. 1, 2, 3, 4
- Meta-analysis demonstrates that VKA plus single antiplatelet therapy (SAPT) significantly reduces recurrent arterial thrombosis compared to VKA alone (RR: 0.43; 95% CI: 0.22-0.85). 4
- Combined therapy also reduces any recurrent thromboembolism (arterial or venous) compared to VKA alone (RR: 0.41; 95% CI: 0.24-0.69). 4
- The American Heart Association guidelines support warfarin INR 2.0-3.0 plus aspirin for arterial events in APS. 1
- Importantly, combined therapy does not significantly increase major bleeding risk compared to monotherapy. 4
Critical Management Principles
Avoid Direct Oral Anticoagulants (DOACs)
- DOACs are contraindicated in APS, especially for arterial thrombosis and in triple-positive patients. 2, 3, 5, 6
- Meta-analysis shows increased risk of recurrent arterial thrombosis with DOACs versus warfarin (OR 5.17; 95% CI: 1.57-17.04). 6
- Rivaroxaban specifically demonstrated excess thrombotic events in APS trials. 5
Duration of Therapy
- Anticoagulation in APS with thrombotic events should be lifelong, not time-limited. 1, 5
- Recurrence rates without vitamin K antagonist therapy are extremely high in APS. 1
Common Pitfalls
- Do not use aspirin monotherapy for established thrombotic APS—this is inadequate anticoagulation. 1, 2
- Do not escalate to high-intensity warfarin (INR 3.0-4.0) as first-line therapy—evidence does not support this approach. 1
- Do not substitute DOACs for warfarin in APS patients, particularly those with arterial events or triple-positive antibodies. 5, 6
Answer: E. Only B and C are true is INCORRECT because Statement B is false.
The correct answer is that ONLY Statement C is true. Statement A requires warfarin (not aspirin alone), and Statement B incorrectly recommends high-intensity anticoagulation that lacks evidence of benefit.