What is the treatment for catastrophic antiphospholipid syndrome (CAPS)?

Treatment of Catastrophic Antiphospholipid Syndrome (CAPS)

Immediately initiate triple therapy with anticoagulation (heparin followed by warfarin), high-dose glucocorticoids, and plasma exchange—this combination has been associated with improved survival in retrospective studies and represents the current standard of care. 1

Foundation Therapy (First-Line Treatment)

Anticoagulation

• Start therapeutic-dose heparin (unfractionated or low molecular weight heparin) immediately upon diagnosis 1
• Transition to warfarin with target INR 2.0-3.0 for long-term management, which requires indefinite continuation given the persistent thrombotic risk 1, 2
• Ensure proper overlap of parenteral anticoagulation when initiating warfarin therapy 2
• Critical contraindication: Never use direct oral anticoagulants (DOACs) in CAPS or any antiphospholipid syndrome, especially in triple-positive patients (lupus anticoagulant, anticardiolipin, and anti-β2 glycoprotein-I antibodies positive), as they are associated with increased thrombotic events including stroke 1, 3, 2

High-Dose Glucocorticoids

• Administer high-dose intravenous glucocorticoids concurrently with anticoagulation to address the inflammatory component of CAPS 1
• This is a cornerstone of therapy alongside anticoagulation 4, 5

Plasma Exchange

• Initiate plasma exchange promptly as it has been associated with improved survival in retrospective studies 1
• Plasma exchange is preferred over intravenous immunoglobulins (IVIG) as part of standard triple therapy, though IVIG may be used as an alternative 5, 6

Special Consideration: SLE-Associated CAPS

• If CAPS occurs in the setting of systemic lupus erythematosus (SLE) flare, add intravenous cyclophosphamide (500-1000 mg/m² monthly) to address the underlying autoimmune trigger 3, 4
• Synchronize cyclophosphamide administration with plasma exchange when possible 3

Refractory or Relapsing CAPS (Second-Line Therapies)

Rituximab

• Consider rituximab (anti-CD20 monoclonal antibody) for refractory CAPS cases 1, 4, 5
• Rituximab blocks CD20 on B cells, decreasing generation of pathogenic antiphospholipid antibodies 5

Eculizumab

• Consider eculizumab (complement C5 inhibitor) for treatment-resistant cases, as it targets complement activation involved in antiphospholipid antibody-induced tissue injury 1, 7
• Case reports demonstrate sustained remission in recurrent CAPS refractory to conventional therapy, with eculizumab blocking complement activity and preventing further thrombotic events 7
• This therapy has shown efficacy in aborting acute progressive thrombotic events and reversing thrombocytopenia 7

Critical Management Principles

Identify and Treat Precipitating Factors

• Aggressively identify and treat any precipitating diagnoses, particularly infection and SLE flares, as these are critical at the time of diagnosis 4
• Preventive measures in patients with known APS may be effective to avoid development of catastrophic APS 6

Monitoring Considerations

• The mortality rate for CAPS remains high despite treatment, requiring intensive multidisciplinary care 8
• Only anticoagulation has demonstrated a significant effect on prognosis in CAPS patients, though the combination therapy approach is still recommended 5

Common Pitfalls to Avoid

• Never discontinue anticoagulation prematurely—long-term (often indefinite) warfarin therapy is required as antibodies persist and thrombotic risk remains elevated 1, 2
• Never use DOACs instead of warfarin—this is explicitly contraindicated and associated with increased thrombotic risk 1, 3, 2
• Do not delay plasma exchange—early aggressive treatment is essential for survival 1, 6
• Do not overlook associated conditions—failure to identify and treat infection or SLE flare can lead to treatment failure 4