Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jan;30(1):116-122.
doi: 10.1111/hae.14896. Epub 2023 Nov 30.

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

Michael Shu  1 , Caroline Malcolmson  1 , Vanessa Bouskill  2 , Ann Marie Stain  2 , Cindy Wakefield  2 , Victor S Blanchette  1 , Manuel D Carcao  1
Affiliations

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

Michael Shu et al. Haemophilia. 2024 Jan.

Abstract

Introduction: The genetic variant responsible for haemophilia A (HA) significantly impacts endogenous coagulant factor VIII (FVIII:C) level, thus impacting DDAVP responsiveness. Blood group (BG) also impacts FVIII:C 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 FVIII:C levels and DDAVP responsiveness in a single genotype of mild-moderate HA.

Methods: This was a retrospective, single-centre study. BG and FVIII:C levels were obtained for males with the Twillingate variant. One-hour absolute and fold increases in FVIII:C post-DDAVP were calculated. T-tests and Mann-Whitney U tests were used to compare FVIII:C 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 FVIII:C level at age <12 years (medians: 0.05 vs. 0.08 IU/mL; P = .05). Fifteen subjects underwent DDAVP challenges. Mean 1-h FVIII:C 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 FVIII:C increase (0.20 vs. 0.27 IU/mL; P = .10) and FVIII:C fold increase (3.3-fold vs. 3.8-fold; P = .51).

Conclusion: In HA subjects with an identical genotype, BG significantly impacts baseline FVIII:C levels and FVIII:C levels post-DDAVP, but does not impact absolute and fold increases in FVIII:C with DDAVP.

Keywords: blood group antigens; deamino arginine vasopressin (DDAVP); factor VIII; haemophilia A; von Willebrand factor.

PubMed Disclaimer

References

REFERENCES

    1. Castaman G, Matino D. Hemophilia A and B: molecular and clinical similarities and differences. Haematologica. 2019;104(9):1702-1709.
    1. Carcao MD, van den Berg HM, Ljung R, Mancuso ME. PedNet, the Rodin Study G. Correlation between phenotype and genotype in a large unselected cohort of children with severe hemophilia A. Blood. 2013;121(19):3946-3952. S1.
    1. Seary ME, Feldman D, Carcao MD. DDAVP responsiveness in children with mild or moderate haemophilia A correlates with age, endogenous FVIII:c level and with haemophilic genotype. Haemophilia. 2012;18(1):50-55.
    1. Xie YG, Zheng H, Leggo J, Scully MF, Lillicrap D. A founder factor VIII mutation, valine 2016 to alanine, in a population with an extraordinarily high prevalence of mild hemophilia A. Thromb Haemost. 2002;87(1):178-179.
    1. Rydz N, Leggo J, Tinlin S, James P, Lillicrap D. The Canadian National Program for hemophilia mutation testing database: a ten-year review. Am J Hematol. 2013;88(12):1030-1034.