In hemophilia cases where there is uncertainty, especially when your factor level is near the 50% cutoff, genetic testing becomes important, Ragni says.
Women with mild hemophilia who carry the gene are often overlooked when it comes to symptoms and treatment options, noted Margaret Ragni, MD, MPH, professor of medicine and clinical and translational research, Division of Hematology/Oncology, director of the Hemophilia Center of Western PA, and American Society of Hematology expert. In this interview with our Center on Health Equity & Access, she explains why genetic testing is crucial for this population.
Is it common practice to test potential carriers or women who are related to those with hemophilia?
We will know that you are a carrier if you're the daughter of a patient with hemophilia, a man with hemophilia. If you are a female relative of someone who has hemophilia, like your nephew, your uncle, a daughter of a woman who's a carrier, we only know that you have a 50% chance of being a carrier. So that's where testing is critical.
But I would argue testing is critical even if we know you have hemophilia because what the testing will establish is what your factor level is. And in people in whom there's equivocation and we're not sure, we usually use this 50% cutoff, because that's the low range of normal, but you can still be a carrier with a normal level—so we do genotyping.
Now, it's become much more common to do genetic testing. If we already know you're an obligate carrier—that is, that you are a carrier—what we really need is your [factor] level. We don't need to do genotyping because we already know it in your son or your father. But many times that's not known. So, in general, if it's not known in the family, we'll do the whole thing.
But the reason that 50% cutoff is important: [It's] not just for diagnosing a carrier, but also for decisions about how to manage your bleeding, and it's not a clear-cut science. Generally, if you're less than 0.5, you can't have an epidural. They won't let you unless you have treatment that brings your level higher and then you need longer treatment, you may be at greater risk for bleeding, all those sorts of things.
And here's another problem: Some women who are carriers don't even know that they're at risk of being carriers, because, don't forget, back 30 years ago, we had the AIDS epidemic. People didn't even want to talk about it or someone died in the family. So again, it was a hush-hush, we didn't talk about it. And so women were the last to know, and certainly their doctors who were not hemostasis doctors, they’re pediatricians, they’re good upstanding internists or gynecologists, don't think of those things. Why would they?
It's sort of one of those issues when a carrier's first symptom, and most common symptom, is heavy menstrual bleeding, you would think that in the realm of things, you would ask the question, “Do you have any other kind of bleeding? What else is going on, is anybody a bleeder in your family?” Those 2 questions could really pave the way for a lot more things.
But let's just suppose now we have established you are a carrier. One of the problems that can happen is we know during pregnancy, for example, your [factor] level may go up, and that's true for hemophilia A, but not for hemophilia B.
By the way, the other thing I forgot to tell you is, there is now a major movement afoot not to classify them as carriers but as hemophilia A and B. I mean, clearly they're carriers by genetic testing, but by talking about what they are, they're mild hemophilia A if they're above 5%, they're mild hemophilia B if they're above 5% of factor VIIII.
By giving them that name, they're taken more seriously, because physicians believe that bleeding disorders only occur in men [and] cannot occur in women who have to bleed at delivery—and that's part of being a normal woman. But the truth is, they have much more severe bleeding than the normal average woman who has menstrual bleeding, who has bleeding at delivery.