Treatment and Prevention of Thrombotic Events in APS
The correct answer is E: Only B and C are true. Statement A is incorrect because unprovoked venous thrombosis in APS requires vitamin K antagonist therapy (INR 2.0-3.0), not low-dose aspirin monotherapy 1, 2.
Analysis of Each Statement
Statement A: Unprovoked Venous Thrombosis - INCORRECT
Low-dose aspirin alone is inadequate for secondary prevention after unprovoked venous thrombosis in APS. The American College of Chest Physicians explicitly recommends vitamin K antagonist (VKA) therapy with target INR 2.0-3.0 as the standard treatment for patients with APS and prior unprovoked venous thrombosis, not aspirin monotherapy 1, 2.
- Moderate-intensity warfarin (INR 2.0-3.0) provides the optimal balance between thrombosis prevention and bleeding risk for venous thromboembolism in APS 1, 2.
- Low-dose aspirin is reserved for primary prevention in asymptomatic antiphospholipid antibody-positive patients, not for secondary prevention after established venous thrombosis 2.
Statement B: Arterial Thrombosis with High-Intensity Warfarin - INCORRECT
High-intensity warfarin (INR 3-4) as monotherapy for arterial APS increases bleeding without proven additional benefit. The American College of Chest Physicians specifically advises against this approach 1.
- High-intensity warfarin (INR 3.0-4.5) should be avoided as it does not provide additional benefit over moderate intensity but significantly increases bleeding risk 2.
- This contradicts older evidence from 1995 3 that suggested high-intensity warfarin, but current guidelines based on more recent data have moved away from this approach 1, 2.
Statement C: Arterial Thrombosis with Moderate-Intensity Warfarin Plus Aspirin - CORRECT
Moderate-intensity warfarin (INR 2.0-3.0) combined with low-dose aspirin 75-100 mg daily is the recommended strategy for arterial thrombosis in APS. This combination reduces recurrent arterial thrombosis compared to VKA alone 1.
- Meta-analysis data demonstrates that VKA plus single antiplatelet therapy is superior to VKA alone for preventing recurrent arterial thrombosis (RR: 0.43; 95% CI: 0.22-0.85) and any recurrent thromboembolism (RR: 0.41; 95% CI: 0.24-0.69) 4.
- Combined antithrombotic therapy does not significantly increase major bleeding risk compared to single agents 4.
- Warfarin with target INR 2.0-3.0 is reasonable for secondary prevention of arterial events including stroke/TIA in antiphospholipid antibody syndrome 2.
Critical Pitfalls to Avoid
Never use direct oral anticoagulants (DOACs) in arterial APS or triple-positive patients. DOACs are associated with increased thrombotic events compared to warfarin in these high-risk populations, as emphasized by the American Heart Association and American College of Cardiology 1, 2, 4.
- In sensitivity analysis excluding low-quality studies, VKA was significantly more effective than NOACs to prevent recurrent arterial thrombosis (RR: 0.25; 95% CI: 0.07-0.93) 4.
Do not abruptly discontinue anticoagulation therapy as this significantly increases thrombosis risk, with the highest recurrence rate (1.30 per patient-year) occurring during the first six months after cessation 3.