What is the immediate treatment for a pediatric patient with catastrophic anti-phospholipid syndrome (CAPS)?

Pediatric Catastrophic Antiphospholipid Syndrome: Immediate Treatment Protocol

For a pediatric patient with catastrophic antiphospholipid syndrome (CAPS), immediately initiate triple therapy consisting of: (1) therapeutic anticoagulation with intravenous unfractionated heparin or low-molecular-weight heparin, (2) high-dose intravenous corticosteroids (methylprednisolone 10-30 mg/kg/day), and (3) either plasma exchange or intravenous immunoglobulin (IVIG 2 g/kg divided over 2-5 days). 1, 2, 3

Immediate Recognition and Stabilization

CAPS is a life-threatening medical emergency characterized by rapid-onset multiorgan failure from widespread small-vessel thrombosis, occurring in less than 1% of all APS patients but carrying mortality rates of 30-50%. 2, 3

Key diagnostic features to confirm:

• Multiple organ involvement (≥3 organs) developing over days to weeks 3
• Histopathologic evidence of small-vessel occlusion on biopsy (skin, kidney, or other accessible tissue) 3
• Laboratory confirmation of antiphospholipid antibodies (lupus anticoagulant, anticardiolipin antibodies, or anti-beta-2-glycoprotein I antibodies) 3
• Exclusion of other causes of microangiopathic process 3

Triple Therapy Protocol

Component 1: Anticoagulation

• Start therapeutic-dose unfractionated heparin (UFH) intravenously immediately, targeting aPTT 1.5-2.5 times control, OR low-molecular-weight heparin (LMWH) at therapeutic dosing 4, 1
• Continue for minimum 5 days before considering transition to oral anticoagulation 4
• Do not delay anticoagulation even if thrombocytopenia is present, unless life-threatening hemorrhage occurs 1, 2

Component 2: High-Dose Corticosteroids

• Administer methylprednisolone 10-30 mg/kg/day IV (maximum 1 gram/day) for 3-5 days 1, 2, 3
• After pulse therapy, transition to prednisone 1-2 mg/kg/day orally 1, 3
• Corticosteroids suppress the cytokine storm and inflammatory cascade driving the catastrophic process 3

Component 3: Plasma Exchange OR IVIG

• Plasma exchange is preferred for severe cases with rapidly progressive organ failure: perform daily or every other day for 5-7 sessions, replacing 1-1.5 plasma volumes per session 2, 3
• IVIG as alternative: administer 2 g/kg total dose divided over 2-5 days (typically 0.4 g/kg/day for 5 days) 1, 2, 3
• Some experts recommend combining both modalities in the most severe presentations 2, 3

Additional Critical Management Steps

Identify and aggressively treat precipitating factors:

• Start broad-spectrum antibiotics immediately if infection is suspected (infection is the most common trigger) 3
• Discontinue any estrogen-containing medications 3
• Avoid surgical procedures unless absolutely necessary for source control (e.g., amputation of necrotic tissue) 3

Consider cyclophosphamide (500-1000 mg/m² IV) if associated with systemic lupus erythematosus flare or if initial triple therapy fails after 48-72 hours 3

Rituximab (375 mg/m² weekly for 4 weeks) should be considered for refractory cases not responding to standard triple therapy, particularly in very young infants where this has shown success 1, 5

Organ-Specific Supportive Care

• Renal involvement: Initiate dialysis early if acute kidney injury develops; do not wait for uremic symptoms 3
• Pulmonary hemorrhage: Provide mechanical ventilation with lung-protective strategies; consider high-dose corticosteroids 5
• Digital ischemia: Add vasodilators such as iloprost or bosentan for severe ischemia threatening limb viability 5
• Cardiac involvement: Monitor for myocardial infarction, valvular dysfunction, and heart failure 3

Transition to Long-Term Management

After acute stabilization (typically 7-14 days), transition from heparin to vitamin K antagonist (warfarin) targeting INR 2.0-3.0 for venous thrombosis or INR 3.0-4.0 if arterial thrombosis occurred. 4, 1

Continue indefinite anticoagulation given the extremely high recurrence risk after catastrophic presentation. 1, 6

Consider adding hydroxychloroquine (5 mg/kg/day, maximum 400 mg/day) as adjunctive therapy to reduce long-term thrombotic risk, particularly if secondary to systemic lupus erythematosus. 1

Critical Pitfalls to Avoid

• Do not wait for antibody confirmation before starting treatment—CAPS is a clinical diagnosis and antibody results may take days; treat empirically if clinical suspicion is high 2, 3
• Do not use direct oral anticoagulants (DOACs) in pediatric APS, especially high-risk profiles—they are associated with increased thrombotic events compared to warfarin 7
• Do not withhold anticoagulation due to thrombocytopenia unless platelet count is critically low (<20,000/μL) with active bleeding 2
• Do not use platelet transfusions unless life-threatening hemorrhage occurs, as they may paradoxically worsen thrombosis 8
• Recognize that healthy children may have transient antiphospholipid antibodies without clinical significance—CAPS requires both antibodies AND the catastrophic clinical presentation 6

Prognosis and Monitoring

Recovery rate with aggressive triple therapy approaches 70-80%, but mortality remains 20-30% even with optimal treatment. 2, 3

Monitor daily: complete blood count, comprehensive metabolic panel, lactate dehydrogenase, coagulation studies, and organ-specific markers (troponin, BNP, creatinine). 3