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

IF 5.2 2区医学 Q1 HEMATOLOGY

Journal of Thrombosis and Haemostasis Pub Date : 2026-10-01 Epub Date: 2026-07-14 DOI:10.1016/j.jtha.2026.06.043

Laura L. Swystun, Julie Grabell, Megan Hinds, Maria Avgeropoulos, Mackenzie Bowman, Megan Chaigneau, Kali de Repentigny, Mark Belletrutti, Wilma Hopman, Alfonso Iorio, Shannon Jackson, Arun Keepanasseril, Jennifer Leung, Sue Robinson, Natalia Rydz, Michelle Sholzberg, Paula D. James

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引用次数: 0

Abstract

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; r_s = −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 (r_s = 0.622, 95% CI: 0.47-0.737) and Self-BAT score (r_s = 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 (r_s = −0.255, 95% CI: −0.444 to −0.044) and joint health (r_s = −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.

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评估加拿大血友病携带者（CHiC）研究中FVIII/FIX水平、出血评分和健康相关生活质量的决定因素

背景：血友病携带者可出现异常出血和健康相关生活质量（HRQoL）降低。临床表型的决定因素尚不清楚。目的：确定血友病携带者的因子VIII (FVIII)/因子IX （FIX）水平、出血表型和HRQoL的修饰因子。方法：本横断面研究纳入108名≥18岁的加拿大血友病携带者。结果包括自我出血评估工具（Self-BAT）评分、SF-36v2 HRQoL和关节健康。中心实验室检测评估了F8/F9基因型、因子水平和ABO。通过非参数分析、Spearman’s rho和多变量回归来评估相关性。结果：血友病A携带者（N=92）中，Self-BAT与FVIII:C相关（rs=-0.298, 95% CI: -0.482 ~ -0.09）。轻度A型血友病患者的平均VWF:Ag （82.8 IU/dL）低于有症状携带者（129.6 IU/dL）和无症状携带者（164.2 IU/dL）。VWF:Ag和VWFpp/VWF:Ag与FVIII:C （rs=0.622, 95% CI: 0.47 ~ 0.737）和Self-BAT （rs=0.255, 95% CI: 0.043 ~ 0.445）相关。O型血存在于83.3%的轻度A型血友病患者、59.1%的有症状携带者和37.5%的无症状携带者中，并与VWF:Ag降低29.8%、FVIII:C降低15.2%和VWFpp/VWF:Ag升高1.44倍相关。多变量分析证实了FVIII:C与VWF:Ag （B: 0.26, 95% CI: 0.17 ~ 0.34）、Self-BAT与FVIII:C （B: -0.06, 95% CI: -0.1 ~ -0.01）、Self-BAT与ABO （B: -2.73, 95% CI: -5.41 ~ -0.04）之间的相关性。SF-36v2 Physical Component Summary与Self-BAT （rs=-0.255, 95% CI: -0.444至-0.044）和关节健康（rs=-0.325, 95% CI: -0.512至-0.111）相关，而心理健康领域与内疚感和负担感相关。结论：在血友病A携带者中，FVIII:C和Self-BAT与VWF和ABO相关。更好地了解这些决定因素可能会改善与健康相关的结果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Thrombosis and Haemostasis 医学-外周血管病

CiteScore

24.30

自引率

3.80%

发文量

321

审稿时长

1 months

期刊介绍： The Journal of Thrombosis and Haemostasis (JTH) serves as the official journal of the International Society on Thrombosis and Haemostasis. It is dedicated to advancing science related to thrombosis, bleeding disorders, and vascular biology through the dissemination and exchange of information and ideas within the global research community. Types of Publications: The journal publishes a variety of content, including: Original research reports State-of-the-art reviews Brief reports Case reports Invited commentaries on publications in the Journal Forum articles Correspondence Announcements Scope of Contributions: Editors invite contributions from both fundamental and clinical domains. These include: Basic manuscripts on blood coagulation and fibrinolysis Studies on proteins and reactions related to thrombosis and haemostasis Research on blood platelets and their interactions with other biological systems, such as the vessel wall, blood cells, and invading organisms Clinical manuscripts covering various topics including venous thrombosis, arterial disease, hemophilia, bleeding disorders, and platelet diseases Clinical manuscripts may encompass etiology, diagnostics, prognosis, prevention, and treatment strategies.