Eculizumab for refractory thrombosis in antiphospholipid syndrome

Abstract

Antiphospholipid syndrome (APS) is characterized by arterial and/or venous thrombosis with antiphospholipid antibodies. Dysregulation of the complement pathway has been implicated in APS pathophysiology. We report the successful use of eculizumab, an anti-C5 monoclonal antibody, in controlling and preventing recurrent thrombosis in a refractory case of APS. An 18-year-old female was diagnosed with APS after developing extensive, unprovoked deep vein thrombosis (DVT) of axillary, inferior vena cava, and brachiocephalic veins. Thrombophilia evaluation revealed triple-positive lupus anticoagulant, β-2 glycoprotein IgM, IgA, and anticardiolipin antibodies (each >40 U/mL) with persistently positive titers after 12 weeks. She was refractory to multiple anticoagulants alone (enoxaparin, fondaparinux, apixaban, rivaroxaban, and warfarin) with antiplatelet (aspirin and clopidogrel) and adjunctive therapies (hydroxychloroquine, immunosuppression with steroids and rituximab, and plasmapheresis). Despite these, she continued to develop recurrent thrombosis and additionally developed hepatic infarction and pulmonary embolism with failure to decrease titers after 6 weeks of plasma exchange. Following this event, eculizumab (600 mg weekly × 4 weeks followed by 900 mg every 2 weeks) was initiated in combination with fondaparinux, aspirin, clopidogrel, and hydroxychloroquine. She has remained on this regimen without recurrence of thrombosis. Our case suggests that eculizumab may have a role as a therapeutic option in refractory thrombosis in APS.