Rituximab for the Treatment of High Titer Acquired Factor VIII Inhibitor with Long Term Follow up

Acquired factor VIII inhibitors are auto antibodies directed against factor VIII (FVIII) and have a reported incidence of 0.2–1.0 per million individuals per year. It is a rare cause of serious bleeding associated with high mortality. Individuals with high titer antibodies (> 100 Bethesda units (BU)), often have difficulty achieving a complete sustained remission although different strategies have been advocated for these patients. Rituximab has been demonstrated to show efficacy in patients with acquired hemophilia. In this study we retrospectively studied three patients with high titer acquired FVIII inhibitors with long term follow up. Two of the patients were resistant to steroids and Intravenous Immunoglobulin, one patient had received steroids and Cyclophosphamide prior to rituximab therapy. Patients ages were 36, 45 and 48 years, two were women and one male. One of the women has a h/o pregnancy about 8 months ago and other two were thought to have idiopathic inhibitors. The patient’s inhibitor titers ranged from 124–800 BU at the time of treatment with Rituximab. All received 4 weekly infusion of rituximab at 375mg/m². No significant treatment related complication was noted. One patient did not respond to treatment. Two patients had a decline in inhibitor titers. One patient had a gradual drop in titer from 124 BU to 0.00 BU over 18 months. The other responder had a drop in titer from 800 BU to 41 BU in 16 months and then relapsed with significant bleeding and anti factor 8 titers of 700 BU and was retreated with rituximab and had a gradual drop in inhibitor titers to 50 BU over 8 months. The two patients have been followed for 28 and 30 months respectively. The non responder continues to have high tires of antibodies and has been followed for 25 months.

We conclude that in patients with high titer of acquired inhibitors rituximab alone may produce a drop in inhibitor titer but is not sufficient to achieve a complete response. Rituximab in combination with other therapies or novel agents may provide better results,