Descriptive analysis of bleeding symptoms in haemophilia carriers enrolled in the ATHNdataset

Abstract

Background: Several studies have reported that haemophilia carriers have a bleeding tendency independent of factor activity. However, investigations have been fraught with methodological concerns. The ATHNdataset houses the largest data set of haemophilia carriers in the world. We undertook an analysis of haemophilia carriers in this data set using methodologies that characterize bleeding symptoms in carriers.Aim: Determine the proportion of haemophilia carriers who have a normal bleeding score (BLS) and factors that affect the BLS. Methods:The ATHNdataset was queried for haemophilia carriers with a documented BLS. Collected data included demographics, ISTH-BAT score, factor activity level, type of haemophilia (A or B), genotype and geographic residence.Results: Nine hundred twenty-two haemophilia carriers in the ATHNdataset reported a BLS. When adjusted for age, 74% reported a normal score. Logistic regression identified age, factor activity level, ethnicity and region of residence as risk factors for an abnormal score. Conclusions:The majority of haemophilia carriers (74%) in the ATHNdataset had a normal BLS, including the majority (59%) with factor activity levels < 40 IU/dl. Conversely, 24% of haemophilia carriers with a factor activity level >40 IU/dl reported an abnormal BLS. These results are consistent with previous studies of haemophilia carriers. Additional investigation is needed to determine why a majority of haemophilia carriers with low factor activity levels report normal BLSs while a significant minority of haemophilia carriers with normal activity levels report abnormal BLSs.

Health issues in women and girls affected by haemophilia with a focus on nomenclature, heavy menstrual bleeding, and musculoskeletal issues

“…WGH have an increased bleeding phenotype as characterized by a growing number of studies. [16][17][18][19] Bleeding tendency as measured by validated instruments (ISTH Bleeding Assessment Tool) is increased in WGH compared to unaffected females, notable even in the 40%-60% baseline level range. Typically, carriers will have bleeding with minor injuries, bleeding following medical interventions, HMB, muscle hematomas and joint bleeding, ranging from 8% to 16%.…”

“…As aforementioned, there is a general lack of correlation of bleeding to the female with factor deficiency. WGH have an increased bleeding phenotype as characterized by a growing number of studies 16–19 . Bleeding tendency as measured by validated instruments (ISTH Bleeding Assessment Tool) is increased in WGH compared to unaffected females, notable even in the 40%–60% baseline level range.…”

Factor activity levels and bleeding scores in pediatric hemophilia carriers enrolled in the ATHNdataset

“…Several studies over the past few decades have shown that hemophilia carriers also have a bleeding tendency. [1][2][3] Due to random X chromosome inactivation, hemophilia carriers can have wide-ranging factor activity levels. 2,4 Approximately one-fourth of hemophilia carriers seen at hemophilia treatment centers (HTCs) have factor activity levels less than 40 IU/dL and are now classified as having hemophilia.…”

“…2,4 Approximately one-fourth of hemophilia carriers seen at hemophilia treatment centers (HTCs) have factor activity levels less than 40 IU/dL and are now classified as having hemophilia. 1,4 Even amongst carriers seen at HTCs with factor activity levels greater than 40 IU/dL, about one-fourth report abnormal bleeding scores (BLS). 1 Thus, amongst hemophilia carriers, just less than one-half either have hemophilia and/or report abnormal BLS.…”

“…1,4 Even amongst carriers seen at HTCs with factor activity levels greater than 40 IU/dL, about one-fourth report abnormal bleeding scores (BLS). 1 Thus, amongst hemophilia carriers, just less than one-half either have hemophilia and/or report abnormal BLS.…”