Abstract
Arg531His (R531H) mutation was identified from unrelated two Japanese patients with cross reacting material positive (CRM+) mild hemophilia A. Although these patients have the same genetic defect and mild clinical phenotype, FVIII activity differed considerably, between the two. In Patient 1, FVIII activity, measured with 14 different APTT reagents, ranged widely, from 25.2% to 48.1%. There was a negative correlation between reagent pH and R531H measurement. Although the FVIII activity in Patient 2 also showed a discrepancy, the difference was considerably lessened by use of an imidazole buffer for sample dilution solution. This finding suggests that the use of imidazole buffer as a sample diluent is an effective means for reducing the wide range of assay results. As for the results of the present study, FVIII levels associated with the R531H mutation differed with the patients and were greatly influenced by measurement method. It is necessary to establish a standard method that can detect and characterize the mild hemophilia phenotype caused by a particular mutation, such as Arg531His.
