Abstract Number: PB0194
Meeting: ISTH 2022 Congress
Theme: Hemophilia and Rare Bleeding Disorders » Hemophilia - Basic
Background: Inhibitors (anti-FVIII neutralizing antibodies) afflict ~1/3 of severe hemophilia A (HA) patients. Several studies have suggested that Black and Hispanic patients suffer higher inhibitor incidences than their White counterparts. The possible influence of non-synonymous single nucleotide polymorphisms (ns-SNPs) in the F8 gene sequence on inhibitor development has been proposed as a possible race-associated contributing factor, although this hypothesis has been controversial.
Aims: The “My Life Our Future” database contains demographic, clinical and F8 sequence data from >6,000 HA participants, allowing for robust statistical analyses of associations between race/ethnicity, F8 mutation and inhibitors. Aims were to evaluate possible associations between race/ethnicity, F8 sequence variants, and clinical and demographic variables and inhibitors.
Methods: Adjusted regression analysis of data from 2,417 severe and 1,752 mild+moderate HA subjects.
Results: Among mild+moderate HA subjects, inhibitor risk was up to 4X lower in those who expressed higher endogenous, hemophilic FVIII (FVIII:C 6-15% and 16-49% vs. 1-5%, aOR, 0.47, 95%CI: 0.31-0.71 and aOR, 0.25, 95%CI: 13-.48, p < 0.0001). Severe HA due to frameshift or missense mutations carried a lower inhibitor risk than intron-22 inversions (aOR, 0.71, 95%CI: 0.54-0.92 and aOR, 0.22, 95%CI: 0.16-0.32, p < 0.0001). In contrast to some earlier studies, there was no difference in inhibitor risk among subjects with severe HA due to an intron-22 inversion, large structural change or nonsense mutation. Black and Hispanic severe HA subjects had a higher inhibitor risk than Non-Hispanic Whites (aOR, 1.85, 95%CI: 1.40-2.45 and aOR, 1.63, 95%CI: 1.21-2.20), confirming this racial/ethnic/medical disparity; however, F8 ns-SNPs were not associated with inhibitor development.
Conclusion(s): African American and Hispanic severe HA patients are at increased risk of developing inhibitors compared to White nonHispanic patients; race-associated F8 haplotypes were not a significant risk factor. Intron 22 and Intron 1 mutations were associated with similar inhibitor risk to other F8 mutations that preclude intact FVIII protein expression.
To cite this abstract in AMA style:
Pratt K, Ahmed A. Race, ethnicity and F8 mutation type influence inhibitor risk: Analysis of the “My Life Our Future” Hemophilia Database [abstract]. https://abstracts.isth.org/abstract/race-ethnicity-and-f8-mutation-type-influence-inhibitor-risk-analysis-of-the-my-life-our-future-hemophilia-database/. Accessed March 22, 2024.« Back to ISTH 2022 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/race-ethnicity-and-f8-mutation-type-influence-inhibitor-risk-analysis-of-the-my-life-our-future-hemophilia-database/