Treatment and Prevention of Thrombotic Events in APS
Statement B is FALSE and Statement C is TRUE, making E (Only B and C are true) INCORRECT. Statement A is TRUE. Therefore, the correct answer is that only A is true, though this option is not listed.
Let me clarify the evidence-based management for each scenario:
Unprovoked Venous Thrombosis in APS
Statement A is TRUE. For patients with APS and prior unprovoked venous thrombosis, vitamin K antagonist (VKA) therapy with target INR 2.0-3.0 is the standard treatment, NOT low-dose aspirin alone 1, 2. However, the statement appears to confuse primary prevention with secondary prevention. For primary prevention in high-risk aPL-positive patients without prior thrombosis, low-dose aspirin 75-100 mg daily is recommended 1, 2.
- For established APS with venous thromboembolism, moderate-intensity warfarin (INR 2.0-3.0) is recommended for long-term anticoagulation 1, 2, 1
- This provides optimal balance between thrombosis prevention and bleeding risk 2
- The American College of Chest Physicians specifically recommends VKA over aspirin monotherapy for secondary prevention after venous thrombosis 2
Arterial Thrombosis in APS
Statement B (high-intensity warfarin INR 3-4 alone) is FALSE based on current evidence. Two randomized controlled trials demonstrated no superiority of high-intensity warfarin (INR 3.1-4.0) over moderate-intensity warfarin (INR 2.0-3.0) for secondary prevention, with increased bleeding risk (28% vs 11%) in the high-intensity arm 1.
Statement C is TRUE and represents the preferred approach. For arterial thrombosis in APS:
- Moderate-intensity warfarin (INR 2.0-3.0) combined with low-dose aspirin 75-100 mg daily is the recommended strategy 1, 2, 3
- Meta-analysis shows that VKA plus single antiplatelet therapy reduces recurrent arterial thrombosis compared to VKA alone (RR 0.43,95% CI 0.22-0.85) 3
- Combined therapy also reduces any recurrent thromboembolism (RR 0.41,95% CI 0.24-0.69) without significantly increasing major bleeding 3
Key Evidence Supporting Combined Therapy
The rationale for combination therapy in arterial events:
- Platelets play a central role in APS pathophysiology, particularly in arterial thrombosis 4
- The WARSS/APASS study showed that for patients meeting full APS criteria with arterial events, anticoagulation with target INR 2.0-3.0 is reasonable 1
- Retrospective studies including patients with arterial thrombosis concluded that combined anticoagulation with antiplatelet therapy provides superior protection 1, 3
Critical Distinctions and Pitfalls
Avoid these common errors:
- Do not use high-intensity warfarin (INR 3-4) as monotherapy for arterial APS—it increases bleeding without proven additional benefit 1, 2
- Do not use direct oral anticoagulants (DOACs) in arterial APS or triple-positive patients—they are associated with increased thrombotic events compared to warfarin 1, 2
- Do not confuse primary prevention (aspirin alone for high-risk aPL carriers) with secondary prevention (anticoagulation ± aspirin after thrombotic events) 1, 2
The correct answer based on current guidelines: Only statement A (if interpreted as primary prevention) and C are true, making the answer E if we correct statement A's context. However, as written with "unprovoked venous thrombosis" suggesting a prior event, statement A is misleading—such patients need anticoagulation, not aspirin alone.