Abstract

According to the CDC’s 2006 National Hemophilia Data Set, females comprise 0.7% of the moderately and severely affected hemophilia A (HA) population and 1.3% of those similarly affected with hemophilia B (HB) in the US. Since no comprehensive data have been published on this patient group since 1978, we conducted this study to collect and analyze epidemiological, clinical, psychosocial, and molecular genetic data on females with severe (s) or moderate (mod) HA or HB. Potential subjects with factor VIII or IX activity levels <0.06u/ml were identified through the CDC database and direct contact with US hemophilia treatment centers (HTC). HTC personnel extracted information from the medical record on diagnosis, laboratory evaluation, bleeding history, menstrual/pregnancy history, hemophilia treatment and complications, as well as chromosomal and molecular genetic test results when available. Subjects completed a quality of life (QOL) instrument as follows: SF-36 if ≥ 14 years or PEDS-QL if < 14 years. Of 28 females identified, 22 from 18 HTCs agreed to participate in the study. The characteristics of this population are summarized in the table below. Six had HB and 16 had HA. The diagnosis was made after spontaneous bleeding, mostly mucocutaneous, in 73% of the cohort. The bleeding phenotype is also outlined in the table.

In addition to unexpectedly few reports of menorrhagia, 4 women, 2 with severe and 2 with moderate hemophilia, had five live births with minimal complications: no reported miscarriages, one report of placental bleeding, one post-partum hemorrhage. Complications documented in this cohort include 41% with target joints, 14% with hepatitis B surface antigen positivity, and 22% with a positive hepatitis C viral load. Three subjects (14%) developed inhibitors. Karyotype and/or molecular diagnostic studies were available in 73% of the cohort and suggest significant genotypic heterogeneity in this population. With respect to QOL, overall physical and mental health composite scores on the SF-36 did not differ significantly from the general population. In adults, menorrhagia and viral infection appeared to have a negative impact on QOL. These data represent the most comprehensive characterization to date of the epidemiology, clinical presentation, morbidity, and genotypic etiology of moderate and severe hemophilia in the female population. Preliminary analysis also suggests that this population has fewer obstetric/gynecological complications than expected, although the cohort remains relatively young. In order to further characterize genetic mutations in this population, a collaborative study is planned, which will include both US and international subjects. The research was funded by grants from CSL Behring Foundation and the National Hemophilia Foundation.

SHA/HB (<0.01 u/ml)Mod HA/HB (0.01–0.05 u/ml)
Demographics/Presentation 
Subject (# subjects) 14 
HA/HB 13/1 3/5 
Median current age (range) (yrs) 17 (2–45) 26 (12–42) 
Median age at diagnosis (range) (mos) 9 (3–72) 48 (14–312) 
Bleeding History (# subjects) 
Median age at first bleed (range) (mos) 9 (12–18) 14 (6–72) 
Joint bleeds 13/14 7/8 
Mucocutaneous bleeds 10/13 8/8 
Intracranial hemorrhage 1/14 0/8 
Menstrual History (# subjects) 
Currently menstruating 
Menorrhagia (subjective) 0/8 3/7 
Pain at ovulation or menses 5/8 6/7 
SHA/HB (<0.01 u/ml)Mod HA/HB (0.01–0.05 u/ml)
Demographics/Presentation 
Subject (# subjects) 14 
HA/HB 13/1 3/5 
Median current age (range) (yrs) 17 (2–45) 26 (12–42) 
Median age at diagnosis (range) (mos) 9 (3–72) 48 (14–312) 
Bleeding History (# subjects) 
Median age at first bleed (range) (mos) 9 (12–18) 14 (6–72) 
Joint bleeds 13/14 7/8 
Mucocutaneous bleeds 10/13 8/8 
Intracranial hemorrhage 1/14 0/8 
Menstrual History (# subjects) 
Currently menstruating 
Menorrhagia (subjective) 0/8 3/7 
Pain at ovulation or menses 5/8 6/7 

Author notes

Disclosure: No relevant conflicts of interest to declare.