Treatment of acquired hemophilia by the Bonn-Malmö Protocol: documentation of an in vivo immunomodulating concept

Abstract

Acquired hemophilia (AH) is an extremely rare condition in which autoantibodies (inhibitors) against clotting factor VIII induce acute and life-threatening hemorrhagic diathesis because of abnormal blood clotting. The mortality rate of AH is as high as 16%, and current treatment options are associated with adverse side effects. We investigated a therapeutic approach for AH called the modified BonnMalmö Protocol (MBMP). The aims of MBMP include suppression of bleeding, permanent elimination of inhibitors, and development of immune tolerance, thereby avoiding long-term reliance on coagulation products. The protocol included immunoadsorption for inhibitor elimination, factor VIII substitution, intravenous immunoglobulin, and immunosuppression. Thirty-five high-titer patients with critical bleeding who underwent MBMP were evaluated. Bleeding was rapidly controlled during 1 or 2 apheresis sessions, and no subsequent bleeding episodes occurred. Inhibitor levels decreased to undetectable levels within a median of 3 days (95% confidence interval [95% CI], 2-4 days), factor substitution was stopped within a median of 12 days (95% CI, 11-17 days), and treatment was completed within a median of 14 days (95% CI, 12-17 days). Longterm follow-up (7 months-7 years) showed an overall response rate of 88% for complete remission (CR). When cancer patients were excluded, the CR rate was 97%. (Blood. 2005;105:2287-2293)

International recommendations on the diagnosis and treatment of patients with acquired hemophilia A

“…Co-administration of FVIII and immunosuppressive agents in patients with acquired hemophilia has been implemented successfully by several investigators, 62,88,92,93 however it is not clear whether the addition of FVIII achieves any benefit. Immunotolerance should therefore only be used in conjunction with clinical research trials to define the real benefits of this new therapeutic modality, or in life-threatening bleeding situations with no response to standard therapeutic regimens.…”

Postpartum acquired factor VIII inhibitors

“…Stasi and colleagues [72] recently reported a complete remission in a case of postpartum acquired hemophilia A after treatment with rituximab and cyclophosphamide. Finally, 4 cases of postpartum FVIII inhibitors were successfully treated by the modified Bonn-Malmo¨protocol including immunoadsorption, FVIII substitution, intravenous immunoglobulins, and immunosuppression [75].…”

A case of acquired hemophilia A in an elderly female

“…The modified Bonn-Malmo protocol involves administration of high dose Factor VIII, IVIg, and immunosuppression, and has a reported success rate of 91% in all patients and 97% in patients without cancer. No recurrence was noted at a median follow-up of 48 months [20,21]. Other protocols are also available with similar results.…”