What is the treatment for Antiphospholipid Syndrome (APS) with a history of thrombosis?

Treatment of Antiphospholipid Syndrome with History of Thrombosis

For patients with confirmed antiphospholipid syndrome (APS) and a history of thrombosis, warfarin with a target INR of 2.0-3.0 is the recommended first-line treatment to reduce recurrent thrombotic events. 1, 2, 3

Anticoagulation Therapy Algorithm

First-line Treatment:

• Warfarin therapy with target INR 2.0-3.0 1, 2
  • Requires overlapping period of parenteral anticoagulation during initiation
  • Regular INR monitoring essential, especially during initiation phase

Special Situations:

1. Triple-positive APS (positive for lupus anticoagulant, anticardiolipin, and anti-β2 glycoprotein-I antibodies):

   • Warfarin with target INR 2.0-3.0 1
   • DOACs (particularly rivaroxaban) should be avoided due to increased thrombotic risk 1, 2, 4

2. Recurrent thrombosis despite therapeutic INR:

   • Consider increasing target INR to 3.0-4.0 2, 5, 6
   • Consider adding low-dose aspirin (75-100 mg/day) 2, 7

3. APS with arterial thrombosis:

   • Consider higher intensity anticoagulation (INR 3.0-4.0) 1, 2, 5

4. APS with concurrent SLE:

   • Add hydroxychloroquine to reduce thrombosis risk 1, 2

Duration of Therapy

• Indefinite anticoagulation is recommended for most patients with APS and thrombosis 2, 3
• The risk of recurrent thrombosis is highest (1.30 events per patient-year) during the first six months after warfarin discontinuation 5
• Regular reassessment of risk-benefit ratio is necessary 2, 3

Monitoring Considerations

• Regular INR monitoring is essential, with attention to potential interference from lupus anticoagulant 2, 8
• Anti-Xa measurement may be preferred over aPTT for biological monitoring in patients with APS 2, 8
• Control of vascular risk factors is essential in all patients with APS 2

Important Caveats

• DOACs (direct oral anticoagulants) should be avoided in APS patients, especially those with triple-positive antibodies or arterial thrombosis 1, 4
• Studies have shown excess thrombotic events with rivaroxaban compared to warfarin in APS patients 1, 4
• Pregnancy requires switching from warfarin to therapeutic low molecular weight heparin plus low-dose aspirin due to warfarin's teratogenicity 2
• Catastrophic APS requires more aggressive treatment with triple therapy (anticoagulation, high-dose glucocorticoids, and plasma exchange/IVIG) 2

Evidence Quality Assessment

The recommendation for warfarin with target INR 2.0-3.0 is supported by multiple high-quality guidelines, including the 2021 CHEST guideline 1 and the 2021 AHA/ASA guideline 1. While some older studies suggested higher intensity anticoagulation (INR 3.0-4.0) might be more effective 5, 6, more recent guidelines favor moderate intensity (INR 2.0-3.0) to balance thrombosis prevention with bleeding risk.

The evidence against DOACs in APS is strong, with multiple studies showing increased thrombotic risk compared to warfarin, particularly in triple-positive patients 1, 4.