What is the management of Antiphospholipid Antibody Syndrome (APS)?

Management of Antiphospholipid Antibody Syndrome (APS)

For patients with confirmed APS requiring anticoagulation, adjusted-dose vitamin K antagonists (target INR 2.5) are recommended over direct oral anticoagulants (DOACs) during the treatment phase. 1, 2

Diagnosis and Classification

• APS is an autoimmune disorder characterized by antiphospholipid antibodies that induce thrombosis, pregnancy morbidity, and other inflammatory manifestations 2
• Diagnosis requires both clinical criteria (thrombotic events or pregnancy morbidity) and laboratory criteria (persistent presence of antiphospholipid antibodies) 2
• Laboratory testing should include lupus anticoagulant (LAC), anticardiolipin antibodies (aCL), and anti-β2 glycoprotein-I antibodies (aβ2GPI) 2
• Antibodies must be detected on two or more occasions at least 12 weeks apart 2
• Triple positivity (positive for all three antibodies) indicates the highest risk for thrombotic events 2

Management of Thrombotic APS

Primary Prevention

• 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

Venous Thromboembolism

• For venous thrombosis, long-term anticoagulation with vitamin K antagonists (warfarin) with a target INR of 2.0-3.0 is strongly recommended 2, 3
• DOACs are specifically contraindicated in APS, especially in triple-positive patients 4, 5

Arterial Thrombosis

• For arterial thrombosis, higher intensity anticoagulation (INR 3.0-4.0) may be considered 2
• Anticoagulation may be superior to antiplatelet therapy for secondary prevention of arterial events in APS 2

Management of Obstetric APS

• For patients meeting criteria for obstetric APS, combined therapy with low-dose aspirin and prophylactic-dose heparin (usually low molecular weight heparin) is strongly recommended 2, 1
• In pregnant women with thrombotic APS, low-dose aspirin and therapeutic-dose heparin should be used throughout pregnancy and postpartum 2
• For pregnant women with positive antiphospholipid antibodies who don't meet criteria for obstetric or thrombotic APS, prophylactic aspirin (81-100 mg daily) is conditionally recommended, starting before 16 weeks and continuing through delivery 2
• The addition of hydroxychloroquine to standard therapy is conditionally recommended for patients with primary APS 2, 6

Management of Assisted Reproductive Technology (ART) in APS

• In subfertile patients with APS who desire pregnancy, ART should be deferred if disease is moderately or severely active 1
• For patients with obstetric APS undergoing ART, strong recommendation for prophylactic anticoagulation with heparin or LMWH 1
• For patients with thrombotic APS undergoing ART, strong recommendation for therapeutic anticoagulation 1
• Prophylactic LMWH (e.g., enoxaparin 40 mg daily) should be started at the beginning of ovarian stimulation, withheld 24-36 hours prior to oocyte retrieval, and resumed following retrieval 1

Management of Catastrophic APS (CAPS)

• Immediate anticoagulation with heparin followed by long-term warfarin (target INR 2.0-3.0) is the foundation of CAPS treatment 4
• High-dose glucocorticoids should be administered concurrently to address the inflammatory component 4
• Plasma exchange should be initiated promptly and has been associated with improved survival 4
• Rituximab may be considered in refractory CAPS 4
• Eculizumab (complement inhibitor) may be considered in treatment-resistant cases 4

Special Considerations

Thrombocytopenia in APS

• The presence of thrombocytopenia does not appear to reduce thrombotic risk in patients with APS 3
• Treatment of thrombocytopenia may be necessary to facilitate administration of antithrombotic agents 3
• Risks and benefits of antithrombotic therapy must be balanced against the severity of thrombocytopenia and potential bleeding risks 3

Monitoring and Follow-up

• Regular monitoring of anticoagulation therapy is essential, with anti-Xa monitoring for patients on heparin or LMWH 2
• Patients with high-risk profiles require more intensive anticoagulation and closer monitoring 2

Common Pitfalls to Avoid

• Using DOACs instead of warfarin is contraindicated as they have been associated with increased thrombotic risk in APS 4, 5
• Discontinuing anticoagulation too early - long-term (often indefinite) anticoagulation with warfarin is required for thrombotic APS 4, 7
• Failing to recognize and treat catastrophic APS promptly, which requires aggressive combination therapy 4