Evaluation of the determinants of factor VIII and factor IX levels, bleeding score, and health-related quality of life in the Canadian hemophilia carriers (CHiC) study.

BACKGROUND

Hemophilia carriers can experience abnormal bleeding and reduced health-related quality of life (HRQoL). Determinants of clinical phenotype remain unclear.

OBJECTIVES

To identify modifiers of factor VIII (FVIII) and factor IX (FIX) levels, bleeding phenotype, and HRQoL in hemophilia carriers.

METHODS

This cross-sectional study included 108 Canadian hemophilia carriers aged ≥18 years. Outcomes included Self-administered Bleeding Assessment Tool (Self-BAT) scores, 36-Item Short Form Health Survey, version 2 (SF-36v2) HRQoL, and joint health. Central laboratory testing assessed F8/F9 genotypes, factor levels, and ABO group. Associations were evaluated by nonparametric analyses, Spearman's rho, and multivariable regression.

RESULTS

In hemophilia A carriers (N = 92), Self-BAT score correlated with FVIII coagulant activity (FVIII:C; rs = -0.298, 95% CI: -0.482 to -0.09). Participants with mild hemophilia A had lower mean von Willebrand factor (VWF) antigen (VWF:Ag; 82.8 IU/dL) than symptomatic (129.6) and asymptomatic carriers (164.2). VWF:Ag and VWF propeptide (VWFpp)/VWF:Ag ratio correlated with FVIII:C (rs = 0.622, 95% CI: 0.47-0.737) and Self-BAT score (rs = 0.255, 95% CI: 0.043-0.445). Blood type O was present in 83.3% of patients with mild hemophilia A, 59.1% of symptomatic carriers, and 37.5% of asymptomatic carriers and associated with 29.8% lower VWF:Ag, 15.2% lower FVIII:C, and 1.44-fold elevated VWFpp/VWF:Ag. Multivariable analysis confirmed associations between FVIII:C and VWF:Ag (β: 0.26; 95% CI: 0.17-0.34), Self-BAT score and FVIII:C (β: -0.06, 95% CI: -0.1 to -0.01), and Self-BAT score and ABO group (β: -2.73, 95% CI: -5.41 to -0.04). The SF-36v2 Physical Component Summary correlated with Self-BAT score (rs = -0.255, 95% CI: -0.444 to -0.044) and joint health (rs = -0.325, 95% CI: -0.512 to -0.111), while mental health domains were linked with feelings of guilt and burden.

CONCLUSION

In hemophilia A carriers, FVIII:C and Self-BAT score associate with VWF and ABO group. A better understanding of these determinants may improve health-related outcomes.