What is the management and treatment of antiphospholipid syndrome?

Management and Treatment of Antiphospholipid Syndrome

Risk Stratification

All patients with antiphospholipid syndrome must be stratified by antibody profile and clinical manifestations to determine treatment intensity. 1

• High-risk profiles include triple-positive antibodies (lupus anticoagulant + anticardiolipin + anti-β2 glycoprotein-I), double-positive with lupus anticoagulant, or persistently high antibody titers (>80 Units) 1, 2
• Low-risk profiles include isolated anticardiolipin or anti-β2 glycoprotein-I antibodies at low-medium titers (<40 Units) 2
• Triple positivity confers the highest thrombotic risk and requires the most aggressive management 1, 3

Management of Thrombotic APS

Venous Thromboembolism

For patients with venous thrombosis, lifelong warfarin with target INR 2.0-3.0 is the definitive treatment. 1, 3, 2

• Moderate-intensity warfarin (INR 2.0-3.0) provides optimal balance between thrombosis prevention and bleeding risk 1, 3
• Avoid high-intensity warfarin (INR 3.0-4.5) as it increases bleeding risk without additional benefit 1, 3
• For first episode of VTE with transient risk factor, treat for 3 months minimum 4
• For first episode of idiopathic VTE, treat for at least 6-12 months 4
• For recurrent VTE or first episode with documented antiphospholipid antibodies, indefinite anticoagulation is indicated 4

Arterial Thrombosis

For arterial thrombosis including stroke, use either high-intensity warfarin (INR 3.0-4.0) OR moderate-intensity warfarin (INR 2.0-3.0) plus low-dose aspirin (75-100 mg daily). 2, 5

• The optimal intensity remains debated, but combination therapy with moderate-intensity warfarin plus aspirin is increasingly favored 5, 6
• Arterial events require particularly careful monitoring given higher recurrence risk 2

Direct Oral Anticoagulants (DOACs)

DOACs are contraindicated in APS, especially in triple-positive patients and those with arterial thrombosis. 3, 2, 6

• Rivaroxaban specifically shows excess thrombotic events compared to warfarin in APS 3
• If a triple-positive patient is already on a DOAC, immediately transition to warfarin 2
• DOACs may only be considered exceptionally in low-risk venous thrombosis patients with warfarin intolerance, but this remains controversial 5, 6

Management of Obstetric APS

Standard Obstetric APS

For women meeting criteria for obstetric APS, combined therapy with low-dose aspirin (81-100 mg daily) plus prophylactic-dose low molecular weight heparin throughout pregnancy and postpartum is mandatory. 1, 2

• Start aspirin before 16 weeks gestation and continue through delivery 2
• Prophylactic LMWH dosing is typically enoxaparin 40 mg daily or dalteparin 5000 units daily 2

Thrombotic APS in Pregnancy

For pregnant women with prior thrombotic APS, use therapeutic-dose heparin (LMWH) plus low-dose aspirin throughout pregnancy and postpartum. 1, 2

• Monitor anti-Xa levels to ensure therapeutic anticoagulation 2
• Warfarin is teratogenic and absolutely contraindicated during pregnancy 2

Assisted Reproductive Technology (ART)

For patients with obstetric APS undergoing ART, start prophylactic LMWH at the beginning of ovarian stimulation, withhold 24-36 hours before oocyte retrieval, and resume immediately after. 2

• For thrombotic APS patients undergoing ART, use therapeutic anticoagulation throughout 2
• Defer ART if disease is moderately or severely active 2

Primary Prevention in Asymptomatic aPL-Positive Patients

For asymptomatic patients with positive antiphospholipid antibodies who do not meet full APS criteria, low-dose aspirin (75-100 mg daily) is recommended, especially with high-risk antibody profiles. 1, 3, 2

• This applies particularly to triple-positive or double-positive patients without prior thrombosis 1
• Aggressive cardiovascular risk factor modification is essential 6

Adjunctive Therapies

Hydroxychloroquine

Adding hydroxychloroquine to standard therapy is conditionally recommended for patients with primary APS, as it may decrease complications. 2

• Hydroxychloroquine is particularly useful in refractory APS or patients with concurrent systemic lupus erythematosus 2, 7
• Consider for patients with recurrent thrombosis despite adequate anticoagulation 6

Statins

Statins may provide benefit through anti-inflammatory and immunomodulatory properties beyond lipid lowering. 2

• Consider in all APS patients given prothrombotic and inflammatory mechanisms 2

Management of Refractory or Catastrophic APS

For catastrophic APS, immediately initiate aggressive combination therapy with anticoagulation, high-dose corticosteroids, plasma exchange, and intravenous immunoglobulin. 2, 8

• Catastrophic APS is a medical emergency with multi-organ thrombosis requiring ICU-level care 8
• For refractory thrombotic APS despite adequate anticoagulation, consider increasing target INR range or adding hydroxychloroquine 2

Critical Monitoring and Follow-up

Regular INR monitoring is essential, with more intensive monitoring for high-risk patients (triple-positive or double-positive with lupus anticoagulant). 1, 2

• Target INR should be checked at least monthly once stable 1
• For patients on LMWH, monitor anti-Xa levels periodically 2
• Reassess risk-benefit of indefinite anticoagulation periodically 4

Common Pitfalls to Avoid

Never abruptly discontinue anticoagulation therapy as this significantly increases thrombosis risk. 1

• Ensure diagnosis is based on persistent antibody positivity (confirmed at least 12 weeks apart) to avoid misdiagnosis 1, 2
• Defer testing for antiphospholipid antibodies until at least 4-6 weeks after acute thrombosis, as protein levels are altered during acute phase 1, 3
• Avoid oral contraceptives and hormone replacement therapy in women with APS given increased thrombotic risk 9
• Pregnancy and postpartum period are particularly high-risk times requiring intensified monitoring 9