What is the treatment for catastrophic Antiphospholipid Syndrome (APS)?

Treatment of Catastrophic Antiphospholipid Syndrome

Catastrophic APS requires immediate triple therapy with anticoagulation (heparin followed by warfarin), high-dose glucocorticoids, and plasma exchange or intravenous immunoglobulins—this combination approach has been associated with improved survival in retrospective studies. 1

First-Line Treatment Components

Anticoagulation (Foundation of Therapy)

• Initiate immediate anticoagulation with intravenous heparin as the cornerstone of CAPS treatment 1, 2
• Transition to long-term warfarin therapy with target INR 2.0-3.0 after stabilization 1
• Ensure proper overlap of parenteral anticoagulation when initiating warfarin 1
• Never use direct oral anticoagulants (DOACs)—they are specifically contraindicated in APS, particularly in triple-positive patients, due to increased thrombotic risk 1, 3

Immunosuppression

• Administer high-dose glucocorticoids concurrently to address the inflammatory cytokine storm that characterizes CAPS 1, 2
• The excessive cytokine release worsens the critical clinical situation and must be suppressed 2, 4

Plasma-Based Therapies

• Initiate plasma exchange promptly—this has been associated with improved survival in retrospective studies 1, 2
• Alternatively, use intravenous immunoglobulins if plasma exchange is unavailable or contraindicated 5, 2
• The combination of anticoagulation, corticosteroids, plus either plasma exchange or IVIG represents the standard treatment approach 5, 2

Treatment of Precipitating Factors

Identifying and aggressively treating precipitating factors is critical, as most CAPS episodes are triggered by infections, surgical procedures, or malignancies 4:

• Prompt use of antibiotics if infection is suspected 2
• Surgical intervention including amputation for necrotic organs 2
• High awareness and preventive measures in APS patients undergoing operations or invasive procedures 2

Special Considerations for SLE-Associated CAPS

• Add cyclophosphamide if CAPS is associated with systemic lupus erythematosus flare 6, 2
• This addresses the underlying autoimmune disease contributing to the catastrophic presentation 2

Second-Line and Refractory Cases

Emerging Biologic Therapies

• Rituximab has shown potential efficacy in case reports and should be considered in refractory CAPS 1, 6
• Eculizumab (complement inhibitor) has emerging evidence in treatment-resistant cases, targeting complement activation involved in antiphospholipid antibody-induced tissue injury 1, 4
• These agents warrant consideration when standard triple therapy fails 6

Critical Pitfalls to Avoid

• Never discontinue anticoagulation prematurely—long-term (often indefinite) anticoagulation with warfarin is required given the persistent thrombotic risk 1, 3
• Do not use DOACs instead of warfarin—this is associated with excess thrombotic events and is contraindicated 1, 3
• Do not delay treatment while awaiting confirmatory testing—CAPS requires immediate aggressive intervention based on clinical suspicion 5, 7
• Failure to recognize and treat precipitating factors (especially infection) can lead to treatment failure 2, 4

Prognosis

Despite aggressive multimodal treatment, mortality remains approximately 30% 4. Early recognition and immediate initiation of combination therapy is essential for survival 5, 7. The disease typically involves kidneys, lungs, and heart, though any organ system can be affected, usually through small vessel thrombosis leading to disseminated microangiopathic syndrome 4.