Efficacy of Rituximab for Recalcitrant Idiopathic Acquired Hemophilia.

Abstract

Idiopathic acquired hemophilia is an extremely rare disorder with a known incidence of only 1.34 cases per million. Although the exact etiology is obscure, it is known that it is due to auto antibodies against factor VIII. It is also associated with severe mortality and morbidity. However, the management of acquired hemophilia is extremely controversial. We present this case study to bring attention to the novel use of rituximab in the management of this rare disorder. A 93 year old white male patient with history of coronary artery disease presented with three weeks of anorexia, weakness, anemia and spontaneous bruising. Examination was impressive for numerous ecchymosis and a developing thigh and scrotal hematoma. He denied any trauma or recent new drugs. His personal or family history was negative for bleeding diathesis. Workup at his internist’s office revealed anemia (Hb -7.4 g %), normal platelet and white cell count, elevated partial thromboplastin time (PTT-62.3s), with normal prothrombin time and fibrinogen concentration. Coombs test, anticardiolipin and lupus anticoagulant antibodies were negative. Immunological tests, biochemical and tumor markers were negative. Whole body computed tomographic scan did not reveal any pathological images. An inhibitor screen was positive and further workup revealed the Factor VIII activity was less than 4% (50–150%) and factor VIII Bethesda inhibitor assay was elevated at 12U/mL(0–0.8 U/mL), leading to the diagnosis of idiopathic acquired hemophilia. His management was originally supportive with multiple transfusions to maintain his hemoglobin above 8.0g%. Attention was then turned to immunosuppression with steroids and cyclophosphamide. His hematomas continued to progress with further drops in his hemoglobin, requiring a total of 14 units of packed RBC’s. In addition, his PTT remained elevated and he was given numerous doses of pro-coagulant preparations (antihemophilic factor/Von Willebrand factor complex, recombinant (r) factor VIII, and rVIIa). However, his PTT and Bethesda inhibitor level remained elevated. At this point, the patient received four weekly doses of rituximab, after which his PTT trended towards normal, with the disappearance of the Bethesda inhibitor and partial restoration of his factor VIII levels. There were no reported side effects. A very aggressive approach has to be undertaken when a diagnosis of acquired inhibitor to coagulation factor is made, with the goal of controlling the bleeding and eradicating the inhibitor. Elimination of the inhibitor with immunosuppressive therapy is definitive unlike the temporizing measures using coagulation factor replacement. There have been few reports in the literature of the successful use of rituximab, an anti-CD20 monoclonal antibody, in the management of this disorder. A four weekly infusion of rituximab costs a fraction of the treatment with pro-coagulant preparations. We believe that given the lack of side- effects and the relatively quick response, we suggest that rituximab may be tried as front line treatment for patients with idiopathic acquired hemphilia.