Definition of Catastrophic Antiphospholipid Syndrome (CAPS)
Catastrophic Antiphospholipid Syndrome (CAPS) is characterized by thrombosis, often of rapid onset, affecting multiple organs simultaneously, and is associated with high mortality. 1
Diagnostic Criteria
CAPS is defined by the following key elements:
- Multiple organ thromboses: Development of multiple vascular thromboses affecting multiple organ systems over a very short period of time
- Small vessel involvement: Histopathological evidence of multiple small vessel occlusions
- Antiphospholipid antibodies: Laboratory confirmation of persistent antiphospholipid antibodies (aPL), usually in high titer 2
- Rapid progression: Clinical manifestations developing rapidly, often leading to multi-organ failure
Epidemiology and Risk
- CAPS represents less than 1% of all antiphospholipid syndrome (APS) cases 2, 3
- Despite its rarity, CAPS carries an overall mortality rate of approximately 36.9% 4
- Patients with triple-positive antibody profile (lupus anticoagulant, anticardiolipin, and anti-β2 glycoprotein-I) are at highest risk 5
Clinical Manifestations
The most commonly affected organ systems in CAPS include:
- Cardiopulmonary system: Characterized by dyspnea and respiratory failure
- Central nervous system: Various neurological manifestations
- Renal system: Acute kidney injury and renal failure
- Multiple organ involvement: The combination of pulmonary, cardiac, and renal involvement is most frequently observed 3
Laboratory Features
Diagnostic laboratory findings include:
- Persistent antiphospholipid antibodies:
- Lupus anticoagulant (LA)
- Anticardiolipin antibodies (aCL) - moderate to high titers (>40 Units)
- Anti-β2 glycoprotein I antibodies (aβ2GPI) 5
- Confirmation of persistence: Antibodies must be detected at least 12 weeks apart 5
- Evidence of thrombotic microangiopathy: Laboratory markers of organ dysfunction corresponding to clinical manifestations
Treatment Approach
Treatment of CAPS requires aggressive intervention with:
- Anticoagulation: Typically with heparin initially, followed by long-term vitamin K antagonists (warfarin)
- High-dose glucocorticoids: To address the inflammatory component
- Plasma exchange: Often used in CAPS and associated with improved patient survival in retrospective studies 1
- Intravenous immunoglobulin: Frequently used alongside other therapies 6
Emerging Therapies
For refractory cases, several targeted therapies may be considered:
- Rituximab: Anecdotal reports suggest potential efficacy 1
- Eculizumab: Emerging evidence supports the use of this complement inhibitor, as complement activation is involved in the pathogenesis of tissue injury induced by aPL 1, 4
- Other potential agents: Hydroxychloroquine, sirolimus, and defibrotide have been proposed for CAPS patients not responding to traditional treatments 7
Important Clinical Considerations
- Direct oral anticoagulants (DOACs) are not recommended for patients with APS and triple-positive antibodies due to increased thrombotic risk compared to warfarin 1, 5
- Pregnancy planning requires multidisciplinary consultation, and estrogen-containing contraceptives should be avoided in women with APS 5
- Regular monitoring of disease activity and vascular risk factors is essential 5
CAPS represents a medical emergency requiring prompt recognition and aggressive treatment to improve survival outcomes. The rapid progression of thromboses across multiple organ systems distinguishes it from classic APS and necessitates immediate therapeutic intervention.