What is the treatment for Antiphospholipid Syndrome (APS)?

Treatment for Antiphospholipid Syndrome (APS)

For patients with confirmed antiphospholipid syndrome (APS), vitamin K antagonists (VKAs) such as warfarin with a target INR of 2.5 (range 2.0-3.0) are recommended as first-line therapy over direct oral anticoagulants (DOACs). 1

Standard Treatment Approach

First-line Therapy

• Vitamin K antagonists (VKAs):
  • Target INR: 2.0-3.0 (target 2.5) 1, 2
  • Requires overlapping period of parenteral anticoagulation during initiation 1
  • Indefinite therapy while antiphospholipid antibodies persist 2

High-Risk APS Patients

For patients with recurrent thrombosis despite therapeutic INR or those with high-risk features:

• Consider increasing INR target range to 3.0-4.0 2
• Alternative: Add low-dose aspirin (75-100 mg/day) to standard warfarin therapy 2, 3

DOACs Should Be Avoided

• DOACs (including rivaroxaban) are not recommended for APS patients 1, 4
• Particularly contraindicated in:
  • Triple-positive APS patients (positive for lupus anticoagulant, anticardiolipin, and anti-β2-glycoprotein-I antibodies) 1, 4
  • Patients with arterial thrombosis 1
  • Higher rates of recurrent thrombotic events compared to VKA therapy 4, 5

Special Clinical Scenarios

Catastrophic APS (CAPS)

Requires triple therapy approach:

1. Therapeutic anticoagulation
2. High-dose glucocorticoids
3. Plasma exchange and/or intravenous immunoglobulins 2

Pregnancy with APS

• Low molecular weight heparin (LMWH) plus low-dose aspirin 2
• Warfarin is contraindicated due to teratogenicity 2

APS with Systemic Lupus Erythematosus

• Consider adding hydroxychloroquine to reduce thrombosis risk 2

Anticoagulant-Refractory APS

For patients who experience recurrent thrombosis despite adequate anticoagulation:

• Consider increasing VKA intensity (higher INR target) 6
• Alternative options include:
  • Switching to LMWH 6
  • Adding antiplatelet therapy 6
  • Consider immunomodulatory therapy in selected cases 6

Monitoring Considerations

• Regular INR monitoring is essential 2, 7
• Be aware that lupus anticoagulant can affect phospholipid-dependent coagulation tests 7
• Measurement of anti-Xa is preferred over aPTT for biological monitoring 2
• Control of vascular risk factors is essential in all APS patients 2

Risk Factors for Recurrent Thrombosis

Patients with the following features may have higher risk of thrombotic recurrence:

• History of multiple prior thrombotic events 5
• Combined arterial and venous thrombosis history 5
• Need for immunosuppressant treatment 5

The evidence strongly supports that long-term warfarin therapy with a target INR of 2.0-3.0 is more beneficial than short-term therapy or lower intensity anticoagulation 8. For patients with recurrent thrombosis despite standard therapy, increasing the intensity of anticoagulation (INR >3.0) may provide better protection 8, 3.