What is the primary treatment for Antiphospholipid Syndrome (APS)?

Primary Treatment for Antiphospholipid Syndrome (APS)

For patients with confirmed Antiphospholipid Syndrome (APS), adjusted-dose vitamin K antagonists (warfarin) with a target INR of 2.0-3.0 is the primary treatment of choice for thrombotic APS. 1, 2

Treatment Based on APS Classification

Thrombotic APS

• Long-term anticoagulation with vitamin K antagonists (warfarin) with target INR 2.0-3.0 is strongly recommended for venous thrombosis 1, 2, 3
• For arterial thrombosis, either higher intensity anticoagulation (INR 3.0-4.0) or standard intensity warfarin (INR 2.0-3.0) plus low-dose aspirin may be considered 2, 4
• Direct oral anticoagulants (DOACs) such as apixaban and rivaroxaban are NOT recommended for APS, especially in triple-positive patients (positive for lupus anticoagulant, anticardiolipin, and anti-β2-glycoprotein-I antibodies) 1, 5, 6
• FDA drug labels specifically warn against using DOACs in triple-positive APS patients due to increased rates of recurrent thrombotic events compared with vitamin K antagonist therapy 5, 6

Obstetric APS

• Combined therapy with low-dose aspirin (81-100 mg daily) and prophylactic-dose heparin (usually low molecular weight heparin) is strongly recommended 1, 2
• Treatment should begin early in pregnancy (before 16 weeks) and continue through delivery 1
• For pregnant women with thrombotic APS, therapeutic-dose heparin plus low-dose aspirin should be used throughout pregnancy and postpartum 1, 2
• Addition of hydroxychloroquine may be beneficial for patients with primary APS, as recent studies suggest it may decrease complications 1, 2

Primary Thromboprophylaxis

• For asymptomatic antiphospholipid antibody-positive patients, low-dose aspirin (75-100 mg daily) is recommended for primary prevention, especially in those with high-risk antibody profiles 2, 7
• For pregnant women with positive antiphospholipid antibodies who don't meet criteria for APS, prophylactic aspirin (81-100 mg daily) is conditionally recommended 1, 2

Special Considerations

Triple-Positive APS Patients

• Patients with triple-positive APS (positive for lupus anticoagulant, anticardiolipin, and anti-β2-glycoprotein-I antibodies) are at highest risk for thrombotic events 2
• DOACs should be strictly avoided in triple-positive patients 1, 5, 6
• If a triple-positive APS patient is already on a DOAC, they should be transitioned to warfarin therapy 1

Catastrophic APS

• Aggressive treatment with a combination of anticoagulation, glucocorticoids, and plasma exchange is recommended 2

Refractory APS

• For patients who fail standard therapy, additional options may include:
  • Increasing the target INR range 1
  • Adding antiplatelet therapy to anticoagulation 3
  • Hydroxychloroquine as adjunctive therapy 1, 8
  • Rituximab, intravenous immunoglobulin, or calcineurin inhibitors in select cases 8

Duration of Treatment

• For thrombotic APS, long-term (indefinite) anticoagulation is generally recommended due to high risk of recurrence 4, 8
• Some studies suggest that anticoagulation might be safely discontinued in selected low-risk patients whose antiphospholipid antibodies become persistently negative, but this requires careful consideration 9

Monitoring

• Regular INR monitoring is essential for patients on warfarin 2
• Patients with high-risk profiles require closer monitoring 2
• Anti-Xa monitoring for patients on heparin or low molecular weight heparin 2

Common Pitfalls and Caveats

• DOACs are increasingly used for venous thromboembolism but are contraindicated in APS, especially triple-positive patients 1, 5, 6
• Thrombocytopenia can complicate management and limit the use of antithrombotic therapy, requiring individualized assessment of thrombotic vs. bleeding risk 10
• Estrogen-containing contraceptives are strongly contraindicated in women with positive antiphospholipid antibodies due to increased thrombosis risk 7