Treatment of acquired hemophilia by the Bonn-Malmo 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 Bonn-Malmo 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%.

• Authors: Heike Zeitler, Gudrun Ulrich-Merzenich, Lothar Hess, Eligius Konsek, Christoph Unkrig, Peter Walger, Hans Vetter, Hans-Hermann Brackmann
• Journal: Blood (Blood) Vol. 105 Issue 6 Pg. 2287-93 (Mar 15 2005) ISSN: 0006-4971 [Print] United States
• PMID: 15542586 (Publication Type: Journal Article)

Chemical References

• Autoantibodies
• Drug Combinations
• Immunoglobulin G
• Immunoglobulins, Intravenous
• Immunologic Factors
• Cyclophosphamide
• Factor VII
• Factor VIII
• Factor IX

Topics

• Adult
• Aged
• Aged, 80 and over
• Autoantibodies (blood)
• Autoimmune Diseases (blood, mortality, therapy)
• Blood Component Removal
• Cyclophosphamide (administration & dosage)
• Disease-Free Survival
• Drug Combinations
• Factor IX (administration & dosage)
• Factor VII (administration & dosage)
• Factor VIII (administration & dosage, analysis, therapeutic use)
• Female
• Follow-Up Studies
• Hemophilia A (blood, mortality, therapy)
• Hemorrhage (immunology, mortality, therapy)
• Humans
• Immune Tolerance (drug effects)
• Immunoglobulin G (administration & dosage)
• Immunoglobulins, Intravenous (administration & dosage)
• Immunologic Factors (administration & dosage)
• Male
• Middle Aged
• Remission Induction
• Retrospective Studies
• Survival Rate