ORLANDO – The traditional view that women who are hemophilia carriers are unaffected by the disease may not be accurate, because many hemophilia carriers experience abnormal bleeding, a hemophilia specialist contends.
“We do know that hemophilia carriers have increased bleeding scores compared to controls,” said Michelle Sholzberg, MD, a hematologist and medical director of the coagulation laboratory at St. Michael’s Hospital in Toronto.
Dr. Michelle Sholzberg
Bleeding in carriers is predominantly mucocutaneous bleeding, and may include epistaxis, heavy menstrual bleeding, bleeding with interventional procedures, and postpartum hemorrhage, she said at the World Federation of Hemophilia World Congress.
The majority of women who carry a factor VIII or factor IX mutation on one X chromosome have factor levels ranging from 0.40 to 0.60 IU/mL, which are generally considered to be adequate for hemostasis.
Yet, “we know that many carriers bleed, and in fact there are carriers who bleed with higher factor levels that are truly in the normal range,” Dr. Sholzberg said.
Normal coagulation factor levels in the general population range from about 0.50 to 1.50 IU/mL. By this standard, approximately 30% of hemophilia carriers have low factor levels, she said.
Joint damage
In addition, 14%-19% of hemophilia A carriers report hemarthrosis, and there is an association in factor VIII or IX deficiencies among hemophilia carriers and reduced joint range of motion. In one study, this decreased range of motion was evident as early as the preteen years, and was suggestive of subclinical musculoskeletal bleeding among carriers. In a separate study, investigators found evidence that hemophilia A carriers have pathologic and radiologic evidence of structural joint damage.
Variability in factor levels among carriers may be caused by lyonization (the inactivation of one of the X-chromosomes), ABO blood type, the presence of mutations in genes encoding for von Willebrand factor, compound heterozygosity or homozygosity, or Turner’s mosaicism.
Clotting factor levels can also change with pregnancy, with hemophilia A carriers experiencing an increase in mean factor VIII levels from 0.46 IU/mL prepregnancy to 1.21 IU/mL in the third trimester, and hemophilia B carriers having a corresponding rise in factor IX levels from 0.31 IU/mL to 0.48 IU/mL, and many carriers still have suboptimal factor levels at pregnancy, Dr. Sholzberg said.
Postpartum hemorrhagic complications among carriers can lead to iron-deficiency anemia. The Centers for Disease Control and Prevention recommends testing all nonpregnant women for anemia every 5-10 years throughout their childbearing years, and annual objective testing for women with risk factors, she noted.
“I think we can all appreciate now that the multidisciplinary approach is important for women with bleeding disorders, and carriers of hemophilia can be safely cared for at HTCs [hemophilia treatment centers],” she said.
Carriers should be treated with a multimodal approach that enhances patient education and awareness, with an emphasis on self-report of symptoms and communication with health care providers.
“It’s also critical never to start a conversation with a woman who has a bleeding disorder with ‘Do you have heavy menstrual bleeding?’ I think we all know that the answer is almost always ‘No, I don’t,’ and that’s because if she has bled heavily for her entire life, she doesn’t know what normal is,” Dr. Sholzberg said.
She described a typical comprehensive care plan for a pregnant hemophilia A carrier. The plan will include information about the diagnosis, recommendations to the obstetricians to avoid the use of invasive instrumentation, anesthesia recommendations, recommendations for care of the mother regarding hemostatic agents, postpartum tranexamic acid, and factor levels, and hematology recommendations for the newborn.
Dr. Sholzberg disclosed research support and/or honoraria from Shire (previously Baxter, Baxalta), Octapharma, CSL Behring, Pfizer, and Novo Nordisk, and advisory committee activity for Shire.