Catastrophic antiphospholipid syndrome (CAPS) is characterized by histopathologic evidence of small vessel thrombosis, dysfunction of multiple organs occurring over a short period of time, and laboratory confirmation of the presence of antiphospholipid antibodies (aPL). Treatment of CAPS focuses on anticoagulation therapy and on removal of aPL that promote thrombosis by activating endothelial cells, monocytes, and platelets. Studies in animal models support the hypothesis that a more targeted intervention, such as complement inhibition, may be an effective means to prevent aPL-induced thrombosis. Herein we describe use of an inhibitor of complement activation to treat CAPS that was refractory to conventional therapy.
Our patient was a young man who had recurrent CAPS characterized by multiple arterial thromboses in large and small vessels despite maximal anticoagulation, immunosuppression, and plasma exchange therapy. We treated him with eculizumab, an anti-C5 monoclonal antibody that blocks activation of terminal complement.
Administration of eculizumab, at doses that blocked complement activity, aborted acute progressive thrombotic events, reversed thrombocytopenia, and was associated with no further clinical episodes of thrombosis during >3 years of therapy.
This first report of the use and clinical efficacy of eculizumab, an inhibitor of complement activation, in the treatment of CAPS demonstrates both the importance of complement (specifically, terminal complement components) in the pathogenesis of CAPS and the therapeutic benefit of complement inactivation.