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Objective. Report of a case of catastrophic antiphospholipid syndrome (CAPS) with multiple organ involvement leading to a life-threatening condition despite early combination corticosteroid and heparin therapy. Initiation of plasma exchange led to rapid improvement of the patient’s general condition. Design. Case report. Setting. University teaching hospital medical intensive care unit. Patient. Single case: 52-year-old man hospitalized for catastrophic antiphospholipid syndrome (CAPS) with cardiac, renal, and cutaneous involvement. Despite early methylprednisolone and heparin therapy, the patient’s condition progressively deteriorated, resulting in acute renal failure, right adrenal hemorrhage, and pulmonary involvement, leading to acute respiratory distress on day 6, requiring high-flow nasal cannula oxygen therapy with FiO2 of 1.0. Interventions. Plasma exchange was started on day 6. Endpoints and Main Results. A marked improvement of the patient’s general condition was observed after initiation of plasma exchange, with successful weaning of oxygen therapy and normalization of platelet count, troponin, and serum creatinine within four days. Conclusions. This case illustrates the efficacy of plasma exchange in CAPS and the difficulty for physicians to determine the optimal timing of plasma exchange.