What is the management of Antiphospholipid Syndrome (APS)?

Management of Antiphospholipid Syndrome (APS)

The cornerstone of APS management is lifelong anticoagulation with warfarin (target INR 2.0-3.0) for thrombotic APS, while obstetric APS requires low molecular weight heparin plus low-dose aspirin during pregnancy. 1, 2

Classification and Initial Approach

• Thrombotic APS: Characterized by venous or arterial thrombosis with persistent antiphospholipid antibodies
• Obstetric APS: Characterized by pregnancy morbidity with persistent antiphospholipid antibodies
• Catastrophic APS: Rapid onset of thrombosis affecting multiple organs with high mortality

Anticoagulation Therapy for Thrombotic APS

First-line Treatment:

• Vitamin K antagonists (warfarin) with target INR 2.0-3.0 1, 2
• For patients with first episode of DVT/PE with documented antiphospholipid antibodies, treatment for at least 12 months is recommended, with indefinite therapy suggested 2

Special Considerations:

• Recurrent arterial thrombosis: Consider higher INR target (>3.0) or addition of low-dose aspirin (75-100 mg/day) 1
• DOACs (direct oral anticoagulants): Not recommended, particularly in triple-positive patients due to increased risk of thrombotic events 1
• Monitoring: Regular INR monitoring is essential; anti-Xa measurement is preferred over aPTT due to potential interference from lupus anticoagulant 1, 3

Management of Obstetric APS

• During pregnancy: Low molecular weight heparin plus low-dose aspirin (75-100 mg/day) 1
• Outside pregnancy: Continue low-dose aspirin 1
• Pre-pregnancy planning: Avoid pregnancy during active lupus nephritis 4

Management of Catastrophic APS

Requires urgent and aggressive treatment:

1. Therapeutic anticoagulation (higher complete response rates of 59.5% vs 30.8%) 4, 1
2. High-dose glucocorticoids 4, 1
3. Plasma exchange (has been associated with improved survival) 4, 1
4. Consider intravenous immunoglobulins 1
5. Eculizumab may be considered in refractory cases 4, 1

Adjunctive Therapies

• Hydroxychloroquine (200-400 mg/day): Recommended especially in APS associated with SLE to reduce thrombosis risk 1
• Control of vascular risk factors in all APS patients 1
• Rituximab: May be considered in refractory cases, particularly for catastrophic APS 4, 1

APS-Associated Nephropathy (APSN)

• Present in 20-30% of patients with SLE 4
• Histological features include thrombotic microangiopathy and chronic lesions such as fibrous intimal hyperplasia
• Treatment includes:
  • Anticoagulation (higher complete response rate of 59.5% vs 30.8% in non-anticoagulated patients) 4
  • Hydroxychloroquine 4
  • Immunosuppressive treatment if nephritis is present 4

Management of Neuropsychiatric Manifestations in APS

• Cognitive dysfunction: May benefit from anticoagulation therapy 4
• Chorea: Symptomatic therapy with dopamine antagonists; consider glucocorticoids with immunosuppressive agents (azathioprine, cyclophosphamide) if active disease; antiplatelet/anticoagulation therapy for antiphospholipid-positive patients 4

Monitoring and Long-term Management

• Regular monitoring of antiphospholipid antibody levels 1
• Evaluation of cutaneous and systemic manifestations 1
• Treatment is generally indefinite while antiphospholipid antibodies persist 1
• In cases of renal transplantation for APS-related end-stage renal disease, perform when clinical (and ideally serological) lupus activity is absent or low for at least 3-6 months 4

Pitfalls and Caveats

• Lupus anticoagulant can affect phospholipid-dependent coagulation tests, leading to inaccurate assessment of anticoagulation intensity 3
• Patients with moderate to high titers of antiphospholipid antibodies are at increased risk for thrombotic complications during renal transplantation and may require perioperative anticoagulation 4
• DOACs have shown inferior results compared to warfarin in preventing thromboembolic events in APS patients 4, 1
• Bridge therapy with low molecular weight heparin should be considered during high-risk procedures 1