Patients with non-severe hemophilia A often show discrepancies in factor VIII (FVIII) activity. However, information on variant-specific coagulation assay characteristics in Japanese patients is limited. Pathogenic variants were classified into three groups, thrombin-cleavage site (TC), A1-A2-A3 interface (IF), and non-discrepant, with reference to previous studies. Cutoff values for the one-stage assay (OSA)/chromogenic substrate assay (CSA) ratio, which is suitable for distinguishing discrepancies, were determined for all five aPTT reagents. TGA and CWA parameters and bleeding scores were compared between groups. Two of the 39 patients with non-severe hemophilia A (5%) were classified as TC, 10 (26%) as IF, and 27 (69%) as non-discrepant. The OSA/CSA cutoff values between the groups varied widely by aPTT reagent and tended to be relatively low compared to previous studies. As an indicator of bleeding tendency, TGA had a low correlation coefficient for the IF variant, but this was not significant and was comparable to FVIII activity and CWA. Moreover, various parameters and bleeding tendency differed among patients with the same variants. Thus, our findings suggest that it is difficult to adequately assess the bleeding tendency of individual patients, even with the various assessments currently available.
Keywords: Assay discrepancy; Bleeding tendency; Factor VIII; Hemophilia A; Missense mutation; Non-severe.
© 2021. Japanese Society of Hematology.