By Dr. David Clark

Hemophilia Carrier Screening 

12/9/23 A group of physicians and researchers from Belgium pointed out that “Despite multiple awareness-raising initiatives, and in contrast with male persons with hemophilia (PwH), a considerable number of carriers and female PwH still go undiagnosed.”  At the American Society of Hematology (ASH) meeting they presented the early findings of a carrier screening project.

They began by updating the family trees for all of the patients at their center and offering to genetically screen all of the females who hadn’t already been screened.  In 228 families (180 A; 48 B), they found 900 females of which 454 were obligate carriers.  An obligate carrier is a female whose father has/had hemophilia.  She will be a carrier of her father’s mutated gene but may or may not have hemophilia herself.  They also found 118 females who were not carriers, about 13%.  This suggests that if you are a female in a hemophilia family, you only have about a 13% chance of not being a carrier.  They also found eight women who should have been carriers based on the family trees but did not carry their “father’s” mutated gene and were actually not carriers.  With so many subjects, genetic testing is still ongoing, so this is an interim report, but it still shows some concerning results.

Among the carriers of hemophilia B, 29.5% had factor IX levels below 40% of normal (considered the lower limit of normal internationally) and 41.0% had a factor level below 50% (the lower limit of normal in the U.S.).  Note that women have been reported to bleed even with levels in the 60% range.  In the hemophilia B-group, 1.3% of carriers had factor IX levels of 6-15%, 26.9% had levels of 16-39%, 24.4% had levels in the 40-60% range and the rest (about 47%) had levels above 60%.  The proportions for hemophilia A were similar, plus there did not appear to be a significant difference between families with mild, moderate or severe hemophilia.  The only significant difference is that the Bs had more instances of reproductive tract bleeding at 38.9% than the As at 5.7%.

The important finding here is that the average time to diagnosis for the females was seven years later than for the men included in the study as control subjects (members of the same families).  Even for the women with factor levels below 40 or 50%, who actually do have hemophilia, the average age at diagnosis was 31.8 years for the Bs (25.8 for the As).  (Note that Belgium has universal health care.  The numbers in the U.S. may be worse.)  The report concludes with the statement, “The carrier screening efforts that have been initiated at our center, and which should ideally be replicated across the hemophilia community globally, appear as a critical step towards providing equal access to hemophilia diagnosis and care to all potentially affected individuals, regardless of their gender.”  [Krumb E et al., ASH abstract 288]