What is the management approach for catastrophic anti-phospholipid antibody syndrome (CAPS) diagnosis?

Management of Catastrophic Antiphospholipid Syndrome (CAPS)

Catastrophic antiphospholipid syndrome requires immediate aggressive triple therapy with therapeutic anticoagulation (intravenous heparin), high-dose glucocorticoids, and plasma exchange and/or intravenous immunoglobulins to prevent multi-organ failure and death. 1, 2, 3

Immediate Recognition and Precipitating Factors

• Identify and treat precipitating factors immediately, as CAPS is often triggered by infection, surgery, anticoagulation withdrawal, or lupus flare 2, 3
• Obtain blood cultures and initiate broad-spectrum antibiotics if infection is suspected—do not delay treatment while awaiting confirmation 3
• Consider surgical debridement or amputation for any necrotic tissue, as this can perpetuate the thrombotic cascade 3
• Maintain high clinical suspicion in any APS patient undergoing surgery or invasive procedures, as these are known precipitants 3

Foundation Therapy: The Triple Approach

Anticoagulation (Most Critical Component)

• Start therapeutic intravenous unfractionated heparin immediately—this is the only intervention with proven significant effect on prognosis 4
• Transition to oral anticoagulation (warfarin with target INR 2.0-3.0) only after acute phase stabilization 1, 5
• Continue anticoagulation indefinitely, as CAPS survivors remain at extremely high risk for recurrent thrombosis 1

High-Dose Glucocorticoids

• Administer high-dose intravenous methylprednisolone (typically 500-1000 mg daily for 3-5 days) to suppress the cytokine storm 2, 3
• All patients should receive corticosteroids as part of foundation therapy 2

Plasma Exchange and/or Intravenous Immunoglobulins

• Plasma exchange is preferred over IVIG based on registry data showing higher recovery rates when combined with anticoagulation and corticosteroids 3, 5
• Typical plasma exchange protocol: daily sessions for 5-7 days, removing 1-1.5 plasma volumes per session 3
• IVIG (0.4 g/kg daily for 5 days) can be used as alternative or in combination with plasma exchange 3, 5

Special Consideration: Systemic Lupus Erythematosus

• Add intravenous cyclophosphamide if CAPS occurs in the setting of SLE flare, as this addresses the underlying autoimmune trigger 2, 3, 5
• Typical dosing: 500-1000 mg/m² monthly, synchronized with plasma exchange when possible 6

Refractory or Relapsing CAPS

Rituximab (Anti-CD20 Monoclonal Antibody)

• Consider rituximab (375 mg/m² weekly for 4 weeks) for patients failing standard triple therapy 2, 4
• Rituximab depletes B cells and reduces pathogenic antiphospholipid antibody production 4
• Evidence is limited to case series, but shows promise in severe refractory cases 2, 4

Eculizumab (Complement C5 Inhibitor)

• Eculizumab may be considered in life-threatening refractory CAPS, as it blocks complement activation (a key pathogenic mechanism) 2, 4
• Dosing: 900 mg weekly for 4 weeks, then 1200 mg at week 5, followed by 1200 mg every 2 weeks 4
• Critical pitfall: Patients must receive meningococcal vaccination at least 2 weeks before eculizumab, or receive prophylactic antibiotics if vaccination cannot be delayed 4

Monitoring and Supportive Care

• Monitor for multi-organ involvement: renal function (creatinine, urinalysis), cardiac enzymes, liver function tests, platelet count, and neurological status 3
• Provide organ-specific support: dialysis for renal failure, mechanical ventilation for ARDS, vasopressors for shock 3
• Serial imaging (CT or MRI) to identify new thrombotic events in brain, lungs, kidneys, or other organs 3

Critical Pitfalls to Avoid

• Never delay anticoagulation due to thrombocytopenia alone—CAPS thrombocytopenia is consumptive from ongoing thrombosis, and anticoagulation is life-saving 1, 3
• Do not use direct oral anticoagulants (DOACs) in CAPS or any APS patient, as they are associated with increased thrombotic events compared to warfarin 1, 7
• Avoid stopping anticoagulation for procedures unless absolutely necessary and with heparin bridging 3
• Do not attribute multiorgan failure to sepsis alone without considering CAPS in any patient with known or suspected antiphospholipid antibodies 2, 3

Prognosis and Long-Term Management

• CAPS mortality remains approximately 30-50% despite aggressive treatment, emphasizing the need for early recognition 2, 3
• Survivors require lifelong therapeutic anticoagulation with warfarin (INR 2.0-3.0 minimum, consider 3.0-4.0 for arterial events) 1
• Consider adding hydroxychloroquine as adjunctive therapy for long-term management, as it may reduce thrombotic risk 1