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Blood, 15 March 2005, Vol. 105, No. 6, pp. 2287-2293.
Prepublished online as a Blood First Edition Paper on November 12, 2004; DOI 10.1182/blood-2004-05-1811.


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CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS

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

Heike Zeitler, Gudrun Ulrich-Merzenich, Lothar Hess, Eligius Konsek, Christoph Unkrig, Peter Walger, Hans Vetter, and Hans-Hermann Brackmann

From the Medical Policlinic of the University of Bonn; the Institute of Experimental Haematology and Transfusion Medicine, University of Bonn; and the Federal Institute for Pharmaceuticals and Medicinal Products (BfARM), Germany.

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 Bonn-Malmö 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). Long-term 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%.


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