Variation in factor VIII inhibitor reactivity with different commercial factor VIII preparations
- 1 April 1996
- journal article
- Published by Wiley in Haemophilia
- Vol. 2 (2) , 95-99
- https://doi.org/10.1111/j.1365-2516.1996.tb00022.x
Abstract
During treatment of a haemophilia A patient with a high-responding inhibitor against factor VIII coagulant activity (VIII:C), we observed a difference in recovery of VIII:C depending upon which factor concentrate was infused. Inhibitor plasma samples or IgG fraction from seven patients were tested against a panel of seven different commercially available factor VIII concentrates of which five were plasma-derived and two recombinant. In two of the plasma samples, inhibitor titres manifested a wide range of values depending upon which concentrate was used in the test system. Thus, inhibitor neutralization was less and VIII:C recovery greater when factor VIII concentrates containing large amounts of von Willebrand factor were used than when highly purified concentrates containing no von Willebrand factor or only trace amounts were used. In both of these two patients the inhibitor was directed against the light chain of factor VIII, and it is possible that the epitope of the light chain with which the inhibitor reacts is partly blocked by the von Willebrand factor. We conclude that inhibitors may differ in their reactivity with factor VIII molecules contained in clotting factor concentrates, and that there is factor VIII epitope variation between different concentrates. These findings have implications for the selection of concentrates for the treatment of inhibitor patients and the haemostatic effect may be improved if a concentrate giving the lowest inhibitor titre is chosen. Thus, in vitro testing of inhibitor reactivity with a panel of concentrates is recommended when treatment of inhibitor patients with factor VIII concentrates is considered.Keywords
This publication has 15 references indexed in Scilit:
- Kinetic Aspects of the Removal of IgG and Inhibitors in Hemophiliacs Using Protein A Immunoadsorption1Vox Sanguinis, 1991
- Variable inactivation of human factor VIII from different sources by human factor VIII inhibitorsBritish Journal of Haematology, 1991
- Molecular basis of factor VIII inhibition by human antibodies. Antibodies that bind to the factor VIII light chain prevent the interaction of factor VIII with phospholipid.Journal of Clinical Investigation, 1989
- Epitope mapping of human factor VIII inhibitor antibodies by deletion analysis of factor VIII fragments expressed in Escherichia coli.Proceedings of the National Academy of Sciences, 1988
- Induction of Immune Tolerance in Patients with Hemophilia and Antibodies to Factor VIII by Combined Treatment with Intravenous IgG, Cyclophosphamide, and Factor VIIINew England Journal of Medicine, 1988
- A sensitive ELISA for von Willebrand factor (vWf:Ag)Scandinavian Journal of Clinical and Laboratory Investigation, 1987
- Induction of split tolerance and clinical cure in high-responding hemophiliacs with factor IX antibodies.Proceedings of the National Academy of Sciences, 1986
- Localization of human factor FVIII inhibitor epitopes to two polypeptide fragments.Proceedings of the National Academy of Sciences, 1985
- Assay of Factor VIII:C with a Chromogenic SubstrateScandinavian Journal of Haematology, 1984
- Immunosuppressive Treatment in Haemophiliacs with Inhibitors to Factor VIII and Factor IXScandinavian Journal of Haematology, 1976