F8 Variants and Inhibitor Development in a Multiethnic Cohort of Nonsevere Haemophilia A

Abstract

Background: Neutralising antibodies (inhibitors) against factor VIII can result in severe bleeding in persons with nonsevere haemophilia A (NSHA). The INSIGHT study of 1112 persons with NSHA in a predominantly White population identified 19 different F8 missense variants that were associated with inhibitor development.

Objective: To describe the F8 variants and inhibitor development in persons with NSHA in a multiethnic cohort using the My Life, Our Future (MLOF) Research Repository and the American Thrombosis and Hemostasis Network dataset (ATHNdataset).

Methods: The MLOF Research Repository and ATHNdataset were queried for demographic, clinical and genotyping data.

Results: A total of 1805 persons with NSHA with at least one reportable F8 variant and known inhibitor status were included in this study. Inhibitors were developed in 142 (7.9%) persons with NSHA. Inhibitor development occurred in seventy F8 variants, of which the majority (n = 67, 95.7%) were missense variants. These 70 F8 variants were identified in a total of 1006 (55.7%) persons with NSHA. Race or ethnicity was not associated with inhibitors in persons with NSHA.

Conclusion: The MLOF Research Repository identified additional F8 variants where inhibitor development occurred in a multiethnic cohort of NSHA. Identification of these F8 variants can inform both physicians and persons with NSHA to adopt measures to reduce the risk of inhibitor development.

Keywords: ethnicity; genotype; haemophilia A; racial groups; risk.