Catastrophic antiphospholipid syndrome: a CAPS-tivating hematologic disease

Abstract

Catastrophic antiphospholipid syndrome (CAPS) is a rare but life-threatening form of antiphospholipid syndrome (APS) defined by the rapid onset of large and small vessel thrombosis occurring simultaneously across multiple sites, resulting in multiorgan dysfunction. The presence of underlying immune dysfunction causing activation of coagulation and, in many cases, abnormal complement regulation predisposes these patients to thrombotic events. CAPS is often preceded by triggering factors such as infection, surgery, trauma, anticoagulation discontinuation, and malignancy. Given the high mortality rate, which may exceed 50%, prompt recognition and initiation of management is required. The detection of antiphospholipid antibodies and the histopathologic identification of microvascular ischemia via tissue biopsy are required to diagnose CAPS. However, these patients are often too unwell to obtain results and wait for them. As such, investigations should not delay CAPS therapy, especially if there is strong clinical suspicion. Management of CAPS requires “triple therapy” with glucocorticoids, intravenous heparin, therapeutic plasma exchange, and/or intravenous immunoglobulin. Treatment for refractory disease is based on poor-quality evidence but includes anti-CD20 (rituximab) or anticomplement (eculizumab) monoclonal antibodies and other immunosuppressant agents, either alone or in combination. The rarity of this syndrome and the subsequent lack of randomized clinical trials have led to a paucity of high-quality evidence to guide management. Continued international collaboration to expand ongoing CAPS registries will allow a better understanding of the response to newer targeted therapy.