Characterization of the clinical and laboratory phenotype of hemophilia carriers and trends of utilization of hemostatic therapies: analysis of the American Thrombosis and Hemostasis Network dataset

Abstract

Background

Hemophilia carriers (HCs) experience varied bleeding tendencies affecting their quality of life, yet their bleeding phenotype and management remain poorly understood. Since majority of the studies in carriers have focused on women of reproductive age, an unmet need exists to characterize their clinical, laboratory phenotype and treatment patterns across the lifespan.

Objectives

The objective of our study was to investigate the age-dependent clinical and laboratory phenotype of hemophilia carriers across the lifespan. We also aimed to study the longitudinal treatment trends in HCs through analysis of the American Thrombosis and Hemostasis Network dataset.

Methods

We investigated the age-dependent variation of bleeding phenotype, coagulation factor levels, and trends of utilization of factor concentrates and nonfactor hemostatic therapies (antifibrinolytics, 1-desamino-8-D-arginine vasopressin) in HCs using the American Thrombosis and Hemostasis Network dataset from 2010 to 2020. The study included 3663 HCs (2728 hemophilia A, 935 hemophilia B) divided into 3 age groups: 0 to 12, 13 to 49, and >50 years.

Results

Joint bleeding was prevalent across all ages of HCs. While bleeding events were more frequent among HCs within the reproductive-age group, hemophilia B carriers received factor therapy more frequently than hemophilia A carriers (P = .03). Factor (F)VIII activity levels in hemophilia A carriers increased significantly with age (P < .001). Analysis of treatment trends from 2010 to 2020 showed increased utilization of factor concentrates and nonfactor hemostatic therapies among HCs (P < .001 and P = .02, respectively).

Conclusion

Our study confirms prior reports of increased bleeding in reproductive-age HCs and identifies lifelong joint bleeding risk. While the rising trend in hemostatic therapy use suggests growing awareness of bleeding tendencies, age-dependent increase in FVIII levels in hemophilia A carriers emphasizes the need for developing tailored management strategies across the lifespan for this population.