Catastrophic Antiphospholipid Syndrome (CAPS) Diagnosis
CAPS is diagnosed when a patient presents with clinical evidence of multiple organ involvement developing over days to weeks, histopathological evidence of multiple small vessel occlusions, and laboratory confirmation of antiphospholipid antibodies, usually in high titer. 1, 2
Diagnostic Criteria
Clinical Requirements
- Multiple organ involvement developing over a very short period of time (typically less than one week) 1, 2
- Small vessel thrombosis affecting at least three different organ systems simultaneously 1, 2
- Most commonly affected organs include kidneys (71%), lungs (64%), central nervous system (62%), heart (51%), and skin (50%) 2
Laboratory Requirements
- Positive antiphospholipid antibodies confirmed by laboratory testing 1, 2
- Testing must include lupus anticoagulant (LAC), anticardiolipin antibodies (aCL), and anti-β2 glycoprotein-I antibodies (aβ2GPI) 3, 4
- Antibodies are usually present in high titers (≥80 Units for moderate-to-high positivity) 5, 4
- Lupus anticoagulant and anticardiolipin antibodies are the predominant antibodies associated with CAPS 6
Histopathological Confirmation
- Biopsy evidence of multiple small vessel occlusions in affected organs 1, 2
- Microangiopathy affecting small vessels of multiple organs 6
Associated Laboratory Findings
- Thrombocytopenia develops in the majority of cases 6
- Hemolytic anemia occurs less frequently 6
- Disseminated intravascular coagulation may be present 6
Important Diagnostic Considerations
The standard 12-week confirmation requirement for antiphospholipid antibodies does NOT apply in CAPS due to the acute, life-threatening nature of the condition—treatment must be initiated immediately based on clinical presentation and initial positive antibody testing. 4, 1
Treatment of CAPS
Immediate triple therapy with anticoagulation (heparin followed by warfarin), high-dose glucocorticoids, and plasma exchange forms the foundation of CAPS treatment and has been associated with improved survival. 3, 7
First-Line Treatment Protocol
Anticoagulation (Mandatory)
- Initiate heparin immediately upon clinical suspicion 7
- Transition to warfarin with target INR 2.0-3.0 for long-term management 3, 7
- Overlap parenteral anticoagulation with warfarin until therapeutic INR achieved 7
- Long-term (often indefinite) anticoagulation required 7
High-Dose Glucocorticoids (Mandatory)
- Administer concurrently to address the inflammatory component 7
- Typical regimen: intravenous methylprednisolone 500-1000 mg daily for 3-5 days 3
Plasma Exchange (Mandatory)
- Initiate promptly—associated with improved survival in retrospective studies 7
- Continue until clinical improvement observed 8
Intravenous Immunoglobulin (Alternative to Plasma Exchange)
- Can be used as alternative or in combination with plasma exchange 8
- Particularly useful when plasma exchange unavailable or contraindicated 8
Second-Line Therapies for Refractory Cases
Cyclophosphamide
- Add intravenous cyclophosphamide if CAPS occurs in the setting of SLE flare 3
- Typical dosing: 500-1000 mg/m² monthly 3
- Synchronize with plasma exchange when possible 3
Rituximab
- Consider in refractory CAPS not responding to first-line therapy 7, 9
- Case reports and registry data show potential efficacy 9
- Targets B-cell mediated antibody production 9
Eculizumab (Complement Inhibitor)
- Emerging evidence supports use in treatment-resistant cases 7, 6
- Targets complement activation involved in antiphospholipid antibody-mediated tissue injury 7, 6
- Successfully used in cases refractory to conventional therapy 6
Critical Pitfalls to Avoid
Direct Oral Anticoagulants (DOACs) Are Contraindicated
- Never use DOACs in CAPS or any antiphospholipid syndrome 7
- DOACs associated with increased thrombotic risk, especially in triple-positive patients 3, 7
- Warfarin is the only acceptable oral anticoagulant 7
Premature Discontinuation of Anticoagulation
- Do not discontinue anticoagulation after acute episode resolves 7
- Lifelong anticoagulation typically required given underlying APS 7
Delayed Treatment Initiation
- Mortality approaches 50% despite treatment—immediate intervention critical 6, 1
- Do not wait for histopathological confirmation or antibody confirmation at 12 weeks before initiating treatment 1, 8