Results from the My Life, Our Future project identified numerous unique variants, some of which were novel, among patients with hemophilia A and B, and was published in the Journal of Thrombosis and Haemostasis.
“The My Life, Our Future project was developed to improve our understanding of hemophilia through wide-scale access to free hemophilia genotype analysis for patients in the United States,” the authors wrote.
The My Life, Our Future study enrolled 11,341 patients with, or potential genetic carriers of, hemophilia A or B between 2013 and 2017. All patients underwent genotyping for variants. Inhibitor data were analyzed to determine if there was a relationship between inhibitor formation and genotype.
Nearly all patients harbored variants, including 98.2% of men with hemophilia A and 98.1% with hemophilia B. There were a total of 1914 unique variants identified, including 1482 in the F8 and 431 in the F9 genes. Of these, 38.9% were considered novel, including 610 variants identified in F8 and 134 variants in F9.
Inhibitor development was associated with high impact variants. Inhibitors were present among 50% of patients with severe hemophilia A with large gene deletions, complex intron 22 inversions, and no variant found. Large deletions were also associated with higher rates of inhibitors among patients with severe hemophilia B.
Development of inhibitors was also associated with race and ethnicity. There were 30% of Black patients with hemophilia A with inhibitors compared with 19.2% of White patients (P <.0001). Among patients with hemophilia B, 13.1% of Black patients developed inhibitors compared with 4.9% of White patients (P <.0001). In addition, 9.9% of patients of Hispanic, Latino, or Spanish ethnicity reported inhibitors compared with 4.9% of patients who did not (P <.009).
The authors concluded that “we demonstrate that hemophilia genotyping is a high hied test, with reportable variants identified in over 98% of subjects.” They added that “this effort has contributed significantly toward better understanding variation in the F8 and F9 genes in hemophilia and the impact on disease severity and inhibitor formation.”
Disclosures: This study was supported by Biogen/Bioverativ. Please see the original reference for a full list of disclosures.
Johnsen JM, Fletcher SN, Dove A, et al. Results of genetic analysis of 11 341 participants enrolled in the My Life, Our Future hemophilia genotyping initiative in the United States. J Thromb Haemost. Published online June 29, 2022. doi: 10.1111/jth.15805