Unravelling the effect of blood group on FVIII:C levels and response to DDAVP in 20 males with a single genotype (Twillingate Variant) causing Haemophilia A.

ABSTRACT

INTRODUCTION: The genetic variant responsible for haemophilia A (HA) significantly impacts endogenous coagulant factor VIII (FVIIIC) level, thus impacting DDAVP responsiveness. Blood group (BG) also impacts FVIIIC levels, but this is difficult to evaluate in a genetically heterogeneous population. Canada has a large cohort of mild-moderate HA due to a single point variant c.6104T>C, p.Val2035Ala-the Twillingate variant. AIM: To evaluate the impact of BG on endogenous FVIIIC levels and DDAVP responsiveness in a single genotype of mild-moderate HA. METHODS: This was a retrospective, single-centre study. BG and FVIIIC levels were obtained for males with the Twillingate variant. One-hour absolute and fold increases in FVIIIC post-DDAVP were calculated. T-tests and Mann-Whitney U tests were used to compare FVIIIC levels and DDAVP challenge variables between individuals according to BGs (O vs. non-O). RESULTS: Twenty males were included. There were significant differences between BGs (O vs. non-O) in their lowest FVIIIC level at age <12 years (medians 0.05 vs. 0.08 IU/mL; P = .05). Fifteen subjects underwent DDAVP challenges. Mean 1-h FVIIIC were 0.29 (O BG) versus 0.41 IU/mL (non-O BG); P = .04. There were no significant differences between BGs (O vs. non-O) in mean absolute FVIIIC increase (0.20 vs. 0.27 IU/mL; P = .10) and FVIIIC fold increase (3.3-fold vs. 3.8-fold; P = .51). CONCLUSION: In HA subjects with an identical genotype, BG significantly impacts baseline FVIIIC levels and FVIIIC levels post-DDAVP, but does not impact absolute and fold increases in FVIIIC with DDAVP.