Eculizumab for Refractory Thrombosis in Antiphospholipid Syndrome

Introduction:Antiphospholipid syndrome (APS) is characterized by arterial and/or venous thrombosis in the presence of antiphospholipid antibodies. Recently, derangement in the complement pathway has been implicated in APS pathophysiology. Refractory cases of APS with recurrent and potentially fatal thrombosis have prompted use of the monoclonal antibody eculizumab, which inhibits generation of the terminal complement complex. We present the successful use of eculizumab in controlling and preventing recurrent thrombosis in a refractory case of APS. Case Description:An 18-year-old female received a diagnosis of antiphospholipid syndrome after developing extensive unprovoked deep vein thrombosis of axillary, inferior vena caval and brachiocephalic veins. Thrombophilia evaluation revealed triple positivity for lupus anti-coagulant (LA), beta-2 glycoprotein I (GP) IgG 84.9 SGU Units, IgM 76.5 SMU Units, IgA 66.7 SAU Units and strongly positive anti-cardiolipin (aCL) antibodies (each >>40U/mL) with persistent positive titers after 12 weeks of initial evaluation. She was refractory with trials of multiple anticoagulants alone and with antiplatelet and adjunctive therapies. Anticoagulants used were enoxaparin, fondaparinux, apixaban, rivaroxaban, and warfarin; antiplatelet agents used were aspirin and clopidogrel; and adjunctive therapies included hydroxychloroquine, immunosuppression with steroids and rituximab, and plasmapheresis. Despite these interventions, she continued to develop recurrent thrombosis of subclavian, femoral, common femoral, iliac, popliteal and saphenous veins. She additionally developed a potentially life-threatening hepatic infarction and pulmonary embolism, and 6 weeks of plasma exchange failed to decrease antiphospholipid antibody titers. Following this event, eculizumab (600mg weekly x 4 weeks, followed by 900mg once on week 5, followed by 900mg every 2 weeks) was initiated in combination with fondaparinux, aspirin, clopidogrel, and hydroxychloroquine. She has remained on this regimen with additional anticoagulation and antiplatelet therapy without recurrence of thrombosis over the subsequent year. Discussion:Recent evidence has shown complement activation playing a role in pathophysiology of antiphospholipid syndrome. This is thought to occur through C3 and C5a causing platelet and endothelial activation, leading to microvascular thrombosis. Histological evidence of such processes is supported by the demonstration of anti-beta-2 GP1 IgG