By David Clark, Ph.D.
We now recognize women can also have hemophilia, and it is imperative to define diagnostic criteria that apply to them. This is needed for insurance coverage of their treatment as well as their own recognition and self-respect. Imagine if you had to limp around on your damaged joints from doctor to doctor to find one to take you seriously. Too many women in our community have had just that experience. Now, we can give names to their conditions.
An international group of twelve hemophilia treaters and patient advocates has taken on this project under the Scientific and Standardization Committee (SSC) of the International Society on Thrombosis and Haemostasis (ISTH). The project was mainly supported by the NHF, HFA, and the Coalition for Hemophilia B from the U.S., as well as other hemophilia organizations around the world. There was no commercial support. The results were published in an article in the Journal of Thrombosis and Haemostasis on July 31, 2021. [See the complete citation at the end of this article.]
The results are shown in the table below. The same classifications are used for both hemophilia A and B. For factor levels up to 40%, women receive exactly the same diagnoses as their male counterparts. They are classified as severe/moderate/mild based on their factor levels. Above 40%, the tables turn. Men with factor levels above 40% are not considered to have hemophilia in many countries. However, women who are carriers with factor levels above 40% can still have a bleeding diagnosis.
The first thing to recognize is that the term “carrier” is now being returned to its proper definition. Carrier is a genetic description – it does not define a bleeding disorder. A woman is a carrier because she carries a mutated factor VIII or IX gene on her X chromosome that she can pass on to her offspring. She may or may not have a bleeding disorder. Carriers can have normal levels of factor VIII or IX.
Next, we need to discuss the international standard of 40% upper limit for hemophilia. In the U.S., we commonly use 50% as the upper limit for hemophilia and the lower limit for the range of normal factor levels. We recognize men with clotting levels up to 50% may still have mild hemophilia and may need treatment. In the rest of the world, men with levels of 40 – 50% are not considered to have hemophilia.
This gets more complicated because we know women can bleed even at levels up to 60%. We don’t know why they still bleed, but the study’s authors have recognized this and have given women two more categories. If a carrier has a level above 40% and does not have bleeding symptoms, she is classified as an “asymptomatic carrier.” However, if a carrier has a factor VIII or IX level over 40% (with no upper limit) but still has bleeding symptoms, she is classified as a “symptomatic carrier.”
This fuzziness in the over 40% levels could lead to situations where it is now the men who could have trouble getting treated. Going by the international classification, a man with a 50% factor VIII or IX level would not be considered to have mild hemophilia, even if he has bleeding symptoms. Yet, if he were a woman with a 50% level and bleeding symptoms, she would be a symptomatic carrier who might have a better chance of being treated.
In addition, all of the categories are just approximations. It is the best we can do with our current state of knowledge. We know that about 15% of people (men and women) do not bleed according to their category of mild, moderate or severe, as determined by their factor level. For instance, some people classified as severe bleed like moderates. Some people classified as mild bleed much more heavily.
Another term seen is obligate carrier. This is also a genetic description, not a bleeding diagnosis. If you are genetically female (have two X chromosomes) and your father has/had hemophilia, you are an obligate carrier. That means you carry (have inherited) your father’s mutated factor VIII or IX gene. That’s just how genetics works. You may or may not bleed. Of course, the genetics can always mess up – that’s how we get hemophilia in the first place. However, it is extremely unlikely that when your father passes along his mutated factor VIII or IX gene, there is another mutation that actually fixes the gene.
One interesting point in the article is the estimate that for every male with hemophilia, there are 1.6 female carriers. Since many of these female carriers might have bleeding problems, there may actually be more women with hemophilia than men. Tell that to your doctor who says women don’t get hemophilia!
This is all based on averages, and no one is average! That’s why you always have to talk to your doctor about your individual case. No one should bleed, no matter their factor levels.
ABOUT THE AUTHOR
David Clark, PhD. is an independent consultant to the biotechnology, plasma, and tissue industries. He has 35+ years of experience in the development and manufacturing of plasma and tissue products, including factor VIII and factor IX concentrates, primarily with the American Red Cross. Dr. Clark holds a Ph.D. in chemical engineering from Cornell University.
REFERENCE
van Galen Karin PM, et al., A New Hemophilia Carrier Nomenclature to Define Hemophilia in Women and Girls: Communication from the SSC of the ISTH, Journal of Thrombosis and Haemostasis, 19(8), 1883-1887, 2021. https://pubmed.ncbi.nlm.nih.gov/34327828/
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