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

Abstract

Introduction Women and girls affected by haemophilia, including haemophilia carriers (WGH) are at risk of bleeding symptoms that may go unrecognized, including heavy menstrual bleeding (HMB) and musculoskeletal bleeding. Terminology continues to evolve. Aim To describe the current recommendations for nomenclature surrounding WGH, and the current understanding of HMB, iron deficiency, and musculoskeletal complaints in these patients. Methods Literature was reviewed and summarized. Results With regards to nomenclature, women with factor levels less than 50% should be classified as having haemophilia, while carriers with normal levels should be characterized accordingly to symptomatology. HMB and resultant iron deficiency are common among WGH, have a multitude of downstream effects, and maybe overlooked due to stigma around menstruation. Musculoskeletal bleeding and resultant joint changes are increasingly recognized in this population but do not necessarily correlate with factor levels. Conclusion Although progress has been made in the care of WGH, much work remains to further improve their care.

Women and girls with haemophilia: A retrospective cohort study in China

“…In our study, less than half of our WGH reported HMB, which was lower than the proportion (64%) reported in previous study. 21 This to have HMB by history, four reported that their periods were normal (data not shown). Additionally, stigma of menstruation still exists in the Chinese culture and women may consider description of menstrual bleeding symptom a taboo, and not to voluntarily provide the information, or to seek medical management.…”

Closing the Diagnostic Gap in Adolescents and Young Adult Women With Bleeding Disorders

“…This historic misconception is at the root of dismissive attitudes by health care professionals 25 and results in inappropriate care, delayed diagnosis, and impaired quality of life in affected women and girls. 24,26…”

“…Gynecologists often do not recognize the potential for hemophilia-carrier status to confer bleeding risk, which is all the more concerning because female genetic hemophilia carriers have high rates of heavy menstrual bleeding and other bleeding symptoms, regardless of their baseline coagulation factor levels. 22,23 Yet the requisite genetic testing to confirm hemophilia-carrier status, and baseline coagulation factor testing to classify affected individuals either as having hemophilia or as being a symptomatic hemophilia carrier, 24 may not be offered to persons with a known family history of hemophilia. This disparity arises from the longstanding and firmly held belief among many in health care that hemophilia affects only males, and that female hemophilia A and B carriership is not associated with a bleeding phenotype.…”

“…This historic misconception is at the root of dismissive attitudes by health care professionals 25 and results in inappropriate care, delayed diagnosis, and impaired quality of life in affected women and girls. 24,26 The true prevalence of female genetic hemophilia carriers is not known, though it is estimated that there could be between two and five potential carriers for every male with hemophilia. 26 The assumption that female genetic carriers of hemophilia A and B will not be affected, or only rarely affected, is based on the understanding that the process of X chromosome inactivation permits at least half of all cells to express normal factor VIII or factor IX at a level sufficient for normal hemostasis.…”

Skewed X-Chromosome Inactivation and Parental Gonadal Mosaicism Are Implicated in X-Linked Recessive Female Hemophilia Patients

“…Patients with HA and HB are typically males hemizygous and females homozygous, or compound heterozygous for mutant F8, or F9 . Heterozygous females are seldom affected because a normally expressed allele on the other X chromosome can compensate for the genetic defect, unless in conditions of skewed X-chromosome inactivation (XCI), coexistence with additional X-chromosome aberrations that cause the loss of a functional gene, and hermaphrodites, by which the wild-type allele does not express as it usual and symptoms developed [ 2 , 3 , 4 , 5 , 6 ]. We had previously reported one very rare hemophilia female patient who carries a familial deletion across the exon 1–22 of the F8 gene on one X chromosome and possesses a de novo rearrangement (isodicentric X) on another X chromosome that leads to complete loss of a functional F8 gene, demonstrated by multiplex ligation-dependent probe amplification (MLPA) in addition to karyotyping [ 2 ].…”