What is the treatment for catastrophic anti-phospholipid syndrome (CAPS)?

Treatment of Catastrophic Antiphospholipid Syndrome (CAPS)

The treatment of catastrophic antiphospholipid syndrome requires aggressive combination therapy with therapeutic anticoagulation, high-dose corticosteroids, plasma exchange, and intravenous immunoglobulins to reduce the high mortality rate of approximately 30%. 1, 2

First-Line Treatment Approach

Immediate Triple Therapy

1. Anticoagulation

   • Start with intravenous unfractionated heparin immediately 3
   • Transition to long-term oral vitamin K antagonists (warfarin) with INR target 2.0-3.0 1
   • Avoid direct oral anticoagulants (DOACs) in APS patients, particularly in triple-positive patients 1

2. Immunosuppression

   • High-dose corticosteroids (methylprednisolone 1000 mg/day for 3 days, followed by prednisone 1-2 mg/kg/day) 3, 2
   • Add cyclophosphamide if CAPS is associated with systemic lupus erythematosus 2

3. Plasma Exchange

   • Daily plasma exchange for 3-5 days to remove antiphospholipid antibodies and cytokines 3, 2

Additional First-Line Treatment

• Intravenous Immunoglobulins (IVIG)
  • Administer 0.4 g/kg/day for 5 days 3, 2
  • Particularly useful when there is concomitant thrombocytopenia or infection 2

Management of Precipitating Factors

• Identify and treat any precipitating factors immediately:
  • Aggressive antibiotic therapy if infection is suspected 3
  • Surgical intervention for necrotic tissue or source control 3
  • Careful perioperative management for patients requiring procedures 4

Refractory CAPS Management

For patients not responding to first-line therapy:

• Rituximab - Consider for refractory cases 2
• Eculizumab - May be beneficial in treatment-resistant cases 1, 2
• Hydroxychloroquine - Add as adjunctive therapy (200-400 mg/day) 1

Special Considerations

Perioperative Management

• Perioperative plasmapheresis may be required before major surgical procedures 4
• Careful monitoring of anticoagulation parameters is essential, as laboratory tests may be affected by antiphospholipid antibodies 1, 4

Laboratory Monitoring

• Anti-Xa levels are preferred over aPTT for monitoring heparin therapy in CAPS patients 1
• Regular monitoring for thrombocytopenia and hemolytic anemia is essential 5
• Despite widespread intravascular coagulation, blood films typically show only a small number of schistocytes 5

Differential Diagnosis

CAPS must be distinguished from other thrombotic microangiopathies:

• Hemolytic-uremic syndrome
• Thrombotic thrombocytopenic purpura
• Disseminated intravascular coagulation
• Heparin-induced thrombocytopenia 5

Long-term Management

• Indefinite anticoagulation with vitamin K antagonists (target INR 2.0-3.0) 1
• For recurrent thrombosis despite adequate anticoagulation:
  • Consider increasing INR target (>3.0) 1
  • Add low-dose aspirin (75-100 mg/day) 1
  • Consider switching to low molecular weight heparin 1, 6
• Regular monitoring of antiphospholipid antibody levels 1
• Aggressive management of cardiovascular risk factors 1

The key to successful management of CAPS is early recognition, prompt initiation of aggressive combination therapy, and a multidisciplinary approach involving hematology, rheumatology, critical care, and nephrology specialists.