Catastrophic Antiphospholipid Syndrome

Catastrophic antiphospholipid syndrome (CAPS) is a rapidly progressive, multi-organ thrombotic microangiopathy occurring in under 1% of antiphospholipid syndrome, with mortality of about 30 to 40%.

• Definition: involvement of three or more organs, systems or tissues within a week, histological evidence of small vessel occlusion, and antiphospholipid antibodies.

• Triggers (in 50%): infection, surgery, anticoagulation withdrawal, trauma, pregnancy/puerperium, malignancy, drugs, SLE flare.

• "Thrombotic storm" with cytokine release and complement activation (second hit).

• Organs: kidneys (renal failure, hypertension), lungs (ARDS), brain (encephalopathy, stroke), heart, skin (necrosis), liver, adrenals.

• Rapid onset multi-organ failure: acute kidney injury with hypertension, ARDS, encephalopathy, myocardial dysfunction, abdominal pain, gangrene, livedo.

• Fever, thrombocytopenia, schistocytes (microangiopathic haemolysis), DIC-like picture.

• Adrenal infarction with adrenal crisis.

• May be the first presentation of APS in half.

• Preliminary classification: three or more organ involvement, development of manifestations within a week, histopathology of small vessel thrombosis, and antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, anti beta-2 GPI).

• Count with thrombocytopenia, schistocytes, LDH, creatinine, troponin, coagulation (aPTT may be prolonged), D-dimer.

• Biopsy of skin or affected organ showing non-inflammatory thrombosis.

• Exclude TTP (ADAMTS13), HUS, DIC, HIT, sepsis, vasculitis, malignancy.

• Search for trigger: cultures, imaging.

Triple therapy as soon as suspected

• Anticoagulation: unfractionated heparin infusion (target aPTT 1.5 to 2.5 times control or anti-Xa 0.3 to 0.7 units/mL) then warfarin (INR 2.5 to 3.5).

• High dose glucocorticoids: methylprednisolone 1 g IV daily for 3 days, then prednisolone 1 mg/kg.

• Plasma exchange (daily for 5 days, 1 to 1.5 plasma volume with fresh frozen plasma) or IVIG 0.4 g/kg daily for 5 days.

• Add cyclophosphamide 500 to 750 mg/m2 IV for SLE-associated CAPS.

• Refractory: rituximab 375 mg/m2 weekly for 4 doses or 1 g x 2, eculizumab 900 mg weekly for 4 weeks then 1200 mg every 2 weeks (complement inhibition).

• Treat triggers: antibiotics for infection, remove necrotic tissue, correct precipitating factors.

• Supportive intensive care: ventilation, renal replacement therapy, haemodynamic support, blood pressure control.

• Long-term lifelong anticoagulation, hydroxychloroquine, avoid trigger exposures.