Management of hemophilia and hemophilia carriers Free

Introduction: Historically, hemophilia has been viewed as primarily affecting individuals assigned male at birth (“males”) due to its X-linked inheritance, and individuals assigned female (“females”) being primarily referred to as hemophilia carriers. In the last decade, research has called attention to disparities in evaluation and treatment of females with a personal or family risk and findings suggest that females with hemophilia are underdiagnosed, underreported and undertreated. Although national and international definitions and guidelines have been updated in recent years to include language regarding females at risk for hemophilia or removing reference to sex assigned at birth altogether, it is unknown how and if these guidelines have been implemented.

The Mountain States and Mid-Atlantic Regions (MSHN-MAR), each HRSA grantees under the Regional Hemophilia Network Award, are collaborating to improve access to comprehensive care and services at Hemophilia Treatment Centers (HTC) for females. Bi-regional practice guidelines were drafted in November 2024 for females at risk for factor VIII deficiency or carrier status or factor IX deficiency or carrier status. Pilot implementation took place in early 2025. Broad use of revised practice guidelines, based on pilot use, will commence in late 2025 and beyond.

To further understand the current and historic diagnostic workup and management in this population, we studied a cohort of individuals assigned female at birth at risk for hemophilia or hemophilia carrier diagnosis seen for care at the Hemostasis and Thrombosis Center at Oregon Health & Science University (OHSU HTC) prior to implementation of the MSHN-MAR practice guidelines.

Methods: This was a retrospective chart review of females with at least one documented encounter at the OHSU HTC since 2016 diagnosed with factor VIII or factor IX deficiency, hemophilia A or B carrier, deficiency of clotting factor, abnormal uterine bleeding, coagulation defect, or menorrhagia due to blood coagulation disorder. Data extracted included: demographics, historic factor activity levels, genetic testing, age of first test, provider diagnosis terminology, medical record problem list terminology related to hemophilia and/or hemophilia carrier status, and attendance at a comprehensive care visit.

Results: 124 of 165 (75.2%) eligible records had confirmed diagnosis of factor VIII or factor IX deficiency or carrier. Of the 124 subjects, current age ranged from 1-91 years (mean 38.2 years). A factor activity level was recorded in 113 subjects (68.4%). The median FVIII activity level was 43% (1-191%; n=98); the median FIX activity level was 28% (1-81%; n=15). A factor level was not documented in 11 (8.9%) subjects. Fourteen (12.4%) subjects had chromogenic factor activity levels recorded. Forty-three (34.4%) subjects had documented genetic testing. Mean age of first documented factor activity level was 22.8 years (range = 0 days to 40 years).

Of the 71 subjects (57.3%) with a lowest documented factor activity < 50%, the problem list diagnosis recorded included: factor VIII deficiency (47.9%); no diagnosis listed (11.3%); hemophilia A carrier (11.3%); symptomatic hemophilia A carrier (11.3%); factor IX deficiency (16.9%); hemophilic arthropathy (1.4%).

Of the 42 subjects with >50% factor activity level documented, the problem list diagnosis recorded included: hemophilia A carrier (42.5%); factor VIII deficiency (14.3%); no diagnosis listed (11.9%); symptomatic hemophilia A carrier (7.1%); asymptomatic hemophilia A carrier (4.8%); genetic carrier (2.4%); family history of hemophilia A (2.4%); factor IX deficiency (2.4%); hemophilia B carrier (2.4%).

Twenty-seven of 124 (21.8%) subjects had at least one OHSU HTC comprehensive visit recorded. Of those, 24 had factor activity levels <50% (88.9%); 3 had factor activity levels > 50% (11.1%).

Conclusions: Our findings show variability in diagnostic workup with regard to factor activity and genetic testing, recorded diagnosis, and attendance at comprehensive clinic in individuals assigned female at birth at risk for hemophilia or hemophilia carrier at this single HTC. Implementation of newly created bi-regional practice guidelines will be monitored through quality improvement cycles with the aim at improving access for this population through cohesive diagnostic work up and diagnostic terminology.