Quantitative Effects of the Reaction between Factor VIII and Factor VIII Inhibitors

Summary

To study the effects of factor VIII and factor VIII inhibitor on each other an assay was developed in which inhibitor activity could be directly related to units of factor VIII. Inhibitor activity in units per ml is defined as the number of factor VIII units reduced to 0.01 factor VIII unit by 1 ml inhibitor plasma after incubation for 1 h at 37° C. Whereas factor VIII was destroyed by inhibitor in accord with a double-logarithmic relation between initial and 1-h residual factor VIII activities, final inhibitor activity was found to be inversely proportional to the ratio of initial concentrations of factor VIII to inhibitor. The latter process resembles “dilution”, rather than direct neutralization, of inhibitor by factor VIII. These effects were observed both in the system for inhibitor assay and in more concentrated mixtures of factor VIII and inhibitor sources in vitro. Results of infusion of factor VIII into a subject with classic hemophilia and an acquired inhibitor suggested that in vivo and in vitro effects of factor VIII and inhibitor activities on each other are comparable, if not identical.

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