Acute renal failure in a patient with antiphospholipid syndrome and immune thrombocytopenic purpura treated with eltrombopag

Abstract

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the presence of antibodies directed against phospholipid-binding proteins such as beta-2 glycoprotein I and prothrombin, venous and/or arterial thromboembolism, and recurrent fetal loss. To fulfill diagnostic criteria, patients must have thrombotic or obstetrical morbidity and consistently positive antiphospholipid testing on two occasions separated by at least 12 weeks [2]. Other clinical manifestations include thrombocytopenia, renal insufficiency, vasculitis, and cardiac valvular abnormalities. Thrombocytopenia occurs in 20-40% of patients with APS while renal dysfunction develops in ~25% of patients with primary APS [3,4]. Thrombocytopenia is thought to be primarily due to the presence of autoantibodies directed against platelet membrane glycoproteins, although platelet activation and aggregation by APS-associated antibodies have also been implicated. Thrombocytopenia in patients with APS is typically moderate in severity with platelet counts remaining greater than 50,000 cells/mm3 in most cases,so therapy is often unnecessary. When treatment is required, therapies used for immune thrombocytopenic purpura (ITP) are often effective. Corticosteroids, intravenous immunoglobulin, dapsone, and rituximab have all been shown to be effective in APS patients with thrombocytopenia[5-7]. Since November 2008, eltrombopag (Promacta; GlaxoSmithKline,Middlesex, United Kingdom), a nonpeptide thrombopoietin receptor agonist that stimulates the development of megakaryocytes, has been approved for use in the management of chronic ITP. To date, no reports of renal toxicity have emerged with its use. We report the case of a patient with APS and steroid-dependent thrombocytopenia who developed partially reversible acute renal failure after initiation of eltrombopag that recurred on rechallenge.