2003; baxter - Supplements - Haematologica

[Acquired Inhibitors in Non-Hemophiliacs]review paperModified Bonn-Malmö Protocol(MBM-P)haematologica 2003; 88(suppl. n. 12):78-85http://www.haematologica.org/free/immunotolerance2001.pdfL. HESS, H. ZEITLER, CH. UNKRIG, W. NETTEKOVEN,T. ALBERT, R. SCHWAAB, W. EFFENBERGER, J. OLDENBURG,H. VETTER, P. HANFLAND, H.H. BRACKMANNInstitute for Experimental Hematology and Transfusion Medicine,Bonn University Hospital, Hemophilia Center, Bonn,GermanyInhibitor formation against clotting factor VIII is alife-threatening condition with a mortality rate of upto 22 %. We treated 24 patients between 30 and 89years of age, all with high-titer factor VIII inhibitorand life-threatening bleeding, using conventionaltherapies and MBM Protocol, respectively. Fivepatients were treated using conventional treatmentmethods, i.e. immunosuppression or immunomodulation(prednisolone, cyclophosphamide, vincristine,IgG). Two of these patients received additionalimmune tolerance therapy according to the BonnProtocol. Permanent inhibitor elimination wasachieved in only one of the five conventionally treatedpatients. One patient had inhibitor remission fora duration of 12 months, followed by another lifethreateningevent. Thus, a total of four patients wereunsuccessfully treated with conventional therapiesfor nine to 86 months. In three patients, conventionaltherapy was discontinued, and treatmentaccording to the Modified Bonn-Malmö Protocol wasinitiated (successfully in two patients; one had todiscontinue treatment despite good response dueto secondary diseases).In total, we treated 22 patients diagnosed withacquired inhibitor and acute life-threatening bleedingwith the Bonn-Malmö Protocol (MPM-P). MBM-P consists of four treatment elements (immunoadsorption,antigen stimulation (factor VIII), immunoglobulinsubstitution and immunosuppression). Seventeenpatients had completely overcome theinhibitor after a median of 16 apheresis treatmentsand showed normal factor VIII plasma activity. A furtherfour patients had to discontinue treatment dueto secondary diseases. Treatment was unsuccessfulin only 1 patient. Median factor VIII consumptionwas 384,000 units. At the end of July 2001, themedian follow-up period for the 17 patients successfullytreated according to the MBM Protocol wasCorrespondence: Dr. Lothar Hess, Institute for ExperimentalHematology and Transfusion Medicine, Bonn University Hospital,Hemophilia Center, Bonn, Germany.31 months, without any indication of new inhibitoractivities. The follow-up period of conventionallytreated patients was between 13 months and nineyears. Factor consumption in patients treated conventionallywas 56,000 to 4.3 million factor VIII unitsand 777,000 to 15 million FEIBA units. The MBMProtocol offers an economical alternative to conventionalinhibitor treatment. The advantages of theMBM Protocol are rapid control of bleeding withinone or two aphereses (24 to 48 hours), quickinhibitor elimination (median of 16 apheresis treatments),stability of successful outcome (median follow-upof 31 months) and a success rate of 94 %(17 successful vs. 1 failure). Early application of factorVIII using apheresis treatment had an earlyimmunomodulatory effect as well as an early hemostaticeffect. This results in the prevention of secondarybleeding complications and the causal treatmentof existing bleedings.©2003, Ferrata Storti FoundationKey words: hemophilia A, factor VIII,catalytic antibodies, factor VIII inhibitors.Modified Bonn-Malmö Protocol (MBMProtocol)Acquired inhibitors, which are mostly directedagainst Factor VIII of the coagulation system, arean extremely rare disease, with an incidence of0.2 to 1/million/year, 1,2 They are usually oligoorpolyclonal autoantibodies type IgG I and IV;however, IgA and IgM inhibitors against factorVIII have been described as well. 3-5Inhibitor occurrence leads to a decompensationof the coagulation system, resulting in mostly lifethreateningsoft-tissue bleeding. Lethality used tobe 22%. 6,7 The fact that according to recent studieslethality is reduced to 7.5% may be attributableto the availability of coagulative APCC and factorVIIa concentrates. 8 The treatment regimensdirected against autoantibodies are based onimmunosuppression by cyclophosphamide, prednisolone,azathiophrine, vincristine and others.haematologica vol. 88(supplement n. 12):september 2003