Characteristics of Hemophilia in Women

By Dr. David Clark 

12/8/24 

We don’t know much about bleeding in women with hemophilia.  They are estimated to comprise about one-third of all hemophilia patients but data in registries shows a proportion less than 10%.  Thus, there is a lot of missing information which leads to inappropriate management and represents a healthcare disparity.  A group at Yale did a retrospective analysis of patients from their center to help fill the gap in knowledge. 

Using the ISTH classification scheme, female patients were classified as “carriers” if their factor levels were 40% or greater and as “women with hemophilia” if their levels were less than 40%.  [Note that women have been reported to have bleeding issues even with levels into the 60+% range.  In the US, 50% is considered the lower limit of the normal range while in the rest of the world, 40% is the lower limit of normal.]  The subjects included women with either hemophilia A, B or C (factor XI deficiency), but here, we’ll concentrate on the 16 women who either have hemophilia B or are carriers. 

The average age at diagnosis was 16 years.  89% had mild hemophilia with 11% moderate or severe.  89% of the women with hemophilia B were treated at hemophilia treatment centers (HTCs), and 86% of the carriers.  Common manifestations in the entire group (107 subjects with A, B or C) were easy bruising (53% of the group), heavy menstrual bleeding (46%), iron deficiency anemia (45%) and epistaxis (nosebleed, 25%).  Post-partum hemorrhage was reported in 10% of the group and miscarriage in 33%.  About 42% of the B carriers used clotting factor treatment as did 67% of the Bs with hemophilia.  Anti-fibrinolytics (like Amicar) were used by 57% of the B carriers and 67% of the Bs with hemophilia. 

The authors conclude that the study highlights the significant bleeding issues in females with hemophilia as well as in carriers, and that those issues are much worse than in the general population.  They point out substandard care for carriers and women with hemophilia, especially concerning reproductive care.  They advocate for higher inclusion of women in hemophilia registries and clinical studies.  [ASH abstract 2584] 

12/8/24  A similar study from the University of Pittsburgh focused only on hemophilia B.  Their group of 129 subjects included 89 Amish women who all share the same factor IX mutation.  They found a low correlation of bleeding with factor IX level with an R2-value of 0.16.  That means that only about 16% of the observed bleeding cases could be explained by factor level, which is consistent with other studies of bleeding in females. 

One of the surprising findings was that they saw the same high variability between factor level and bleeding rate in the Amish women, who are a fairly homogeneous population.  This all suggests that we are really missing one or more factors that affect bleeding in women, and possibly in men, too.  They also found a high prevalence of iron deficiency with 93% of the subjects with ferritin (the protein that carries iron around the bloodstream) levels below 50 ng/ml.  They recommend routine ferritin screening in women regardless of factor level.  [ASH abstract 2586]