[The modified Bonn Malmö protocol (MBMP) in the treatment of acquired haemophilia A].
OBJECTIVE
Autoantibodies directed against clotting factors can induce life threatening bleeding with a mortality rate up to 22%. Although the incidence of the disease is low (1-4 x 10(-6)), costs of treatment due to long-term clotting factor substitution can be enormous. Aim of an optimal treatment strategy should be to control bleedings by a rapid and safe elimination of the inhibitor and reinducing long-term immune tolerance.


METHODS
Treatment of 48 patients with acquired haemophilia A (m=20, f =28, age 61.3 (SD 16.4)), the largest patient collective world-wide, was monitored for a mean of 48 months. Three patients received only conservative treatment. 45 patients were treated intensively by a multimodal strategy including: 1. immunoadsorption for antibody elimination; 2. FVIII substitution; 3. intravenous immunoglobulin substitution and 4. immunosuppression. The times required for inhibitor elimination, factor VIII substitution and the duration of the MBMP were documented.


RESULTS
In 45 patients with a high titre critical bleeding was controlled immediately after the initiation of MBMP. There were no deaths from bleeding or the treatment. Inhibitor levels decreased to undetectable levels within a median of 3 days (95% CI, 3-7 days), factor substitution was terminated within a median of 13 days (95% CI, 10-16 days) and the treatment was completed within a median of 15 days (95% CI, 13-17 days). The overall response rate for complete remission (CR) was 91%. When cancer patients were excluded, the CR rate was 97%.


CONCLUSIONS
Considering the short duration and amount of factor VIII substitution, the short time of hospitalization and the long-term median follow up of 48 months without bleeding events, the MBMP appears to have a modifying effect on the immunological response.
Zeitler
H
H
Medizinische Poliklinik der Universität Bonn. heike.zeitler@uni-bonn.de
Ulrich-Merzenich
G
G
Walger
P
P
Düsing
R
R
Vetter
H
H
Brackmann
H H
HH
D000368:Aged; D001327:Autoimmune Diseases; D005169:Factor VIII / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006467:Hemophilia A / Q000628:therapy*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007164:Immunosorbents / Q000627:therapeutic use*; D007165:Immunosuppression Therapy; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
D016756:Immunoglobulins, Intravenous; D007164:Immunosorbents; D005169:Factor VIII