What is the treatment for catastrophic antiphospholipid syndrome?

Treatment of Catastrophic Antiphospholipid Syndrome

The treatment of catastrophic antiphospholipid syndrome (CAPS) requires aggressive triple therapy consisting of anticoagulation, high-dose glucocorticoids, and plasma exchange, with consideration of intravenous immunoglobulin in selected cases. 1, 2, 3

First-Line Treatment Approach

Immediate Triple Therapy

1. Anticoagulation:

   • Start with intravenous heparin or low molecular weight heparin (LMWH) 4
   • Transition to long-term warfarin with target INR 2.0-3.0 1
   • DOACs should be avoided, especially in triple-positive patients 5, 1

2. High-dose glucocorticoids:

   • Typically methylprednisolone pulse therapy (1000 mg/day for 3 days) followed by oral prednisone 3
   • Helps suppress the excessive cytokine response

3. Plasma exchange:

   • Removes pathogenic antiphospholipid antibodies
   • Usually performed daily for 3-5 sessions 2

Additional First-Line Options

• Intravenous immunoglobulin (IVIG):
  • Consider as alternative or addition to plasma exchange
  • Typical dose: 0.4 g/kg/day for 5 days 3

Treatment of Precipitating Factors

• Aggressive infection management with broad-spectrum antibiotics if infection is suspected 4
• Surgical intervention for necrotic tissue if present 4
• Treatment of underlying SLE if present (may require cyclophosphamide) 2

Second-Line Therapies for Refractory Cases

Targeted Biological Therapies

• Rituximab:

  • B-cell depleting therapy that reduces pathogenic autoantibody production
  • Consider in refractory cases not responding to triple therapy 2, 3

• Eculizumab:

  • Complement C5 inhibitor that prevents formation of membrane attack complex
  • Emerging evidence supports its use in refractory CAPS 6
  • Blocks one mechanism of antiphospholipid antibody-induced organ damage

Long-Term Management

• Indefinite anticoagulation with warfarin (target INR 2.0-3.0) 1

  • Studies show higher complete response rates (59.5% vs 30.8%) in patients who received anticoagulation 5
  • Anti-Xa measurement is preferable to aPTT for laboratory monitoring in patients with antiphospholipid syndrome 5

• Avoid DOACs in CAPS patients:

  • Multiple guidelines recommend against DOACs in antiphospholipid syndrome 5, 1
  • Particularly important in triple-positive patients (positive for lupus anticoagulant, anti-cardiolipin, and anti-β2-glycoprotein-I antibodies) 5

Monitoring and Follow-up

• Close INR monitoring as antiphospholipid antibodies can affect phospholipid-dependent coagulation tests 1
• Regular assessment of organ function to detect early signs of recurrence
• Hydroxychloroquine maintenance in patients with underlying SLE 5

Clinical Pearls and Pitfalls

• Early recognition and aggressive treatment are essential for survival, as mortality remains high (36.9%) despite optimal therapy 6
• Multidisciplinary approach involving rheumatology, hematology, intensive care, and nephrology is crucial 7
• Anticoagulation has the most significant effect on prognosis among all treatment modalities 3
• Danaparoid sodium (750 anti-Xa IU twice daily) can be considered in patients with heparin-induced thrombocytopenia 5

CAPS represents a medical emergency requiring prompt diagnosis and aggressive treatment. The combination of anticoagulation, glucocorticoids, and plasma exchange forms the cornerstone of therapy, with newer targeted therapies offering hope in refractory cases.