Hemophilia B Classifications for Women

By Dr. David Clark

Now that we are recognizing women can also have hemophilia, it is important to define diagnostic criteria that apply to them. This is needed for insurance coverage of their treatment, but also for their own recognition and self-respect. Imagine if you had to limp around on your damaged joints from doctor to doctor to try to get one to take you seriously. Too many women in our community have had just that experience. Now, we can give names to their problems.

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 Coalition, NHF and HFA 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 for hemophilia B. (Hemophilia A uses the same categories.) For factor IX 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 are turned. Men with factor levels above 40% are not considered to have hemophilia; however, women who are carriers 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 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 IX.

Next, we need to talk about the 40% upper limit for hemophilia. That is the international standard. In the U.S., we commonly use 50% as the upper limit for hemophilia and the lower limit for the normal range of factor levels. We recognize that men with 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% don’t have hemophilia.

This gets more complicated because we know that women can bleed even at levels up to 60%. We don’t know why they still bleed, but the study authors have recognized this and given women two more categories. If a carrier has a level above 40% but does not have bleeding symptoms, she is classified as an “asymptomatic carrier.” However, if a carrier has a factor 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 IX level would not have mild hemophilia, even if he has bleeding symptoms. Yet, if he were a woman with 50%, 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’s the best we can do with our current state of knowledge. We know that up to about 15% of people (men and women) do not bleed according to their category, mild, moderate or severe, as determined by their factor level. For instance, some people who are classified as severe bleed like moderates. Some people who are classified as mild, bleed much more heavily.

Another term seen sometimes 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 just means that you carry (have inherited) your father’s mutated factor IX gene. That’s just how the 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 his mutated factor 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 – 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 what their factor levels are.

[van Galen KPM 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. DOI: 10.1111/jth.15397. The easiest way to access this on the internet is to type “DOI: 10.1111/jth.15397” into your browser. This is an open-access article – you can read or download a copy for free.]