Female carriers of hemophilia have more bleeding symptoms, poorer joint health

Women who are carriers of hemophilia had more bleeding and joint-related symptoms than noncarriers, according to the results of a study presented at the 2023 ASH Annual Meeting.

“Historically, hemophilia has been considered a male disease, leading to the common misconception that hemophilia carriers are asymptomatic and cannot have excessive bleeding. This leads to significant underdiagnosis and delayed treatment in these women,” said Rachel S. Kronenfeld, MD, of the University of Miami Miller School of Medicine when presenting the study.

The Carriers Ultrasound Project (CUP) study was designed to assess the prevalence of joint disease among patients who are carriers of hemophilia. For this purpose, women aged 18 to 40 who were hemophilia carriers (n=30) or healthy controls (n=30) were recruited between 2017 and 2023. Study participants underwent clinical assessment with the Hemophilia Joint Health Score (HJHS), and carriers were assessed for factor activity levels.


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Carriers and controls had a mean age of 31.0 (SD, 6.4) and 26 (SD, 5.4) years, were 90% and 70% white, and had a mean BMI of 26 (SD, 5.4 ) and 24.5 (SD, 4) kg/m2, respectively. Among the carriers, 86.7% were carriers of hemophilia A and 13.3% were carriers of hemophilia B. Hemophilia carriers had a mean level of factor activity of 54%, ranging between 17% and 110%.

More carriers had bleeding symptoms (83.3% vs 13.3%; P <.001), including heavy menstrual bleeding (66.7% vs. 10.0%; P <.001), epistaxis (26.7% vs. 3.3%; P =.011), gingival bleeding (26.7% vs. 3.3%; P =.011) and easily bruised (50.0% vs. 3.3%; P <.001) compared to controls, respectively.

Carriers also had poorer joint health characterized by recurrent joint pain (50% vs. 3.3%; P <.001) and joint swelling (26.7% vs. 0%; P =.002), they had higher HJHS (mean, 5 vs. 1.5; P <.001) and more had abnormal HJHS (83.3% vs. 43.3%; P =.001) compared to controls, respectively.

Controls were not prescribed bleeding medications, while 30% of carriers were prescribed antifibrinolytics (P =.001), 26.7% were prescribed factor substitution on demand (P =.002), and 20% were prescribed desmopressin (P =.01).

Among carriers and stratified by factor activity levels, women with mild hemophilia (n=6) or factor activity ³40% (n=24) did not differ significantly with respect to bleeding or joint symptoms (all P ³.15), suggesting that bleeding and joint symptoms are independent of factor levels. More women with mild hemophilia were prescribed bleeding medications than women with a higher level of factor activity (all P £0.04).

In an exploratory analysis looking at BMI, carriers who had a BMI >25 mg/m22 (n=13) reported more joint bleeds (23.1%) than those with BMI <25 mg/m2 (n=17; 0%; P =.037).

Limitations of this study were the small sample size and the fact that the HJHS raters were not blinded.

Dr. Kronenfeld concluded, “Hemophiliacs are at increased risk for bleeding and joint-related symptoms, regardless of factor activity levels. Our findings highlight the importance of routine follow-up of hemophilia carriers in specialized hemophilia treatment centers… Research to further characterize joint health and related complications in hemophilia carriers is needed and should be a priority in the future.

Disclosures: This research was supported by Bayer Healthcare Pharmaceuticals. Please see the original reference for a complete list of disclosures.

reference

Kronenfeld RS, Fraga K, D’Almeida Bastos M, et al. Assessment of joint health using musculoskeletal ultrasound in female hemophilia carriers: the Carrier Ultrasound Project (CUP) study. Presented at ASH 2023. December 9-12, 2023. San Diego, CA. Summary 29.

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