What is the primary treatment for antiphospholipid syndrome?

Primary Treatment for Antiphospholipid Syndrome

Warfarin with a target INR of 2.0-3.0 is the primary treatment for confirmed antiphospholipid syndrome with thrombotic events, and this should be continued indefinitely as long as antiphospholipid antibodies persist. 1, 2, 3

Treatment Algorithm Based on Clinical Presentation

For Confirmed APS with Prior Thrombosis

Warfarin remains the cornerstone anticoagulant:

• Target INR 2.0-3.0 provides optimal balance between preventing recurrent thrombosis and minimizing bleeding risk 1, 2, 3
• Initiate with overlapping parenteral anticoagulation (heparin or LMWH) until therapeutic INR is achieved 3
• Continue indefinitely—the recurrence rate is highest (1.30 per patient-year) during the first six months after stopping warfarin 4

For arterial thrombosis (including stroke):

• Use moderate-intensity warfarin (INR 2.0-3.0) combined with low-dose aspirin (75 mg daily), OR high-intensity warfarin alone (INR >3.0) 1, 5
• The 2021 AHA/ASA guidelines favor INR 2.0-3.0 over higher targets to balance bleeding risk 1

For venous thrombosis:

• Warfarin with target INR 2.0-3.0 is standard 2, 3
• DOACs may be considered only in low-risk patients (LA-negative, not triple-positive) who cannot tolerate warfarin, though this remains controversial 5, 6

For Triple-Positive APS (Highest Risk)

These patients require the most aggressive approach:

• Mandatory warfarin therapy—never use DOACs 2, 7, 3
• Target INR 2.0-3.0, with strict adherence and monitoring 2
• Triple-positive status (lupus anticoagulant + anticardiolipin + anti-β2 glycoprotein-I antibodies) confers the highest thrombotic risk 2, 3

For Isolated Antiphospholipid Antibodies WITHOUT APS Criteria

Antiplatelet therapy alone is sufficient:

• Low-dose aspirin (75 mg daily) is recommended for patients with positive antibodies who do not meet full APS criteria 1
• This applies to primary prevention in asymptomatic carriers, especially with additional cardiovascular risk factors 1, 6

Critical Contraindications

Direct oral anticoagulants (DOACs) are specifically contraindicated in APS:

• Rivaroxaban causes excess thrombotic events compared to warfarin in triple-positive patients 1, 7
• All DOACs should be avoided in triple-positive APS and arterial thrombosis 2, 7, 3
• The only potential exception is carefully selected low-risk venous thrombosis patients with warfarin intolerance, but this remains high-risk 5

Catastrophic APS (Life-Threatening Presentation)

Requires immediate multimodal therapy:

• Immediate heparin anticoagulation followed by warfarin (INR 2.0-3.0) 7
• High-dose glucocorticoids concurrently 7
• Plasma exchange initiated promptly 7
• Consider rituximab or eculizumab for refractory cases 7

Common Pitfalls to Avoid

Do not use high-intensity warfarin (INR 3.0-4.5) routinely:

• No additional benefit over moderate intensity but significantly increases bleeding risk 2
• Reserve for selected refractory arterial cases only 5

Do not discontinue anticoagulation prematurely:

• APS requires lifelong treatment as long as antibodies persist 3, 8
• Recurrence risk peaks immediately after stopping therapy 4

Do not test for antiphospholipid antibodies during acute thrombosis:

• Protein levels are altered during acute events—wait 4-6 weeks before testing or retesting 1

Do not use DOACs as a "simpler" alternative:

• Despite convenience, they increase thrombotic risk in APS, particularly in high-risk patients 1, 2, 7, 3

Adjunctive Therapies

Consider adding to anticoagulation in complex cases:

• Hydroxychloroquine for patients with concurrent SLE or refractory thrombosis 9, 5
• Statins for additional cardiovascular risk reduction 9
• Address all modifiable cardiovascular risk factors aggressively 6