Genetic Mutation and Signs and Symptoms of Hemophilia


Peter L. Salgo, MD: Thank you for joining us for this unique MD Magazine® Peer Exchange entitled “Advances and MASAC Guideline Recommendations for the Treatment of Hemophilia.” While hemophilia is a rare disorder in which the blood doesn’t clot normally due to insufficient blood-clotting proteins or clotting factors, hemophilia does affect 20,000 individuals in the United States. The more common types are hemophilia A with a factor VIII deficiency and hemophilia B with a factor IX deficiency. We’re going to evaluate the changes in treatment options with new therapies and updated guidelines.

I’m Dr. Peter Salgo. I’m a professor of medicine and anesthesiology at Columbia University College of Physicians here in New York City, and I’m associate director of Surgical Intensive Care at New York Presbyterian Hospital.

Joining me for this discussion is Dr. Christopher Walsh, associate professor of medicine, hematology, and medical oncology at the Icahn School of Medicine at Mount Sinai in New York, New York. In addition to this panel, Dr. Meera Chitlur, pediatric hematologist-oncologist at the Children’s Hospital of Michigan in Detroit, will be providing her perspectives on the treatment of pediatric hemophilia. I want to thank you right now for joining us, and it’s time to begin.

I think our audience, being physicians, knows the word “hemophilia.” They’re associated with it and pretty cognizant of what it is. But why don’t we just get some of the basics down. What is the genetic alteration that we’re looking at here in hemophilia?

Christopher E. Walsh, MD, PhD: Thanks for being here. This is an inherited genetic feedback passed from mother to son. It’s sex-linked, or x-linked, and basically the genes that are involved have multiple mutations. They can be very missense, which are single bases, or where large chunks of the gene are missing or inverted, contorted, if you will. The protein may be there but doesn’t work, or it may be gone, These are different mutations that we have.

Peter L. Salgo, MD: When you’re looking at someone with no family history, as you alluded to, is that because there’s just spontaneous mutation, or because the woman is the carrier and nobody knows about the man’s side?

Christopher E. Walsh, MD, PhD: That’s a great point. Women, female carriers—depending on the mutation and the number of cells in the liver that carry this mutation—can be symptomatic, or asymptomatic and not even know they have this or are carrying the disease. For others, it’s in utero; it’s a spontaneous mutation. It’s all of these.

Peter L. Salgo, MD: You’re not safe just because there’s no family history on either side, this can happen out of the blue. Let’s talk about the different kinds of hemophilia and their prevalence. You alluded to hemophilia A. What are we talking about here?

Christopher E. Walsh, MD, PhD: The estimated prevalence is roughly 1 in 5000 live male births. Hemophilia B is about 1 in 15,000 or 1 in 20,000. It’s estimated, at least in the United States, that there are roughly 20,000 to 25,000 patients in total with hemophilia, and about 4000 of those have hemophilia B.

Peter L. Salgo, MD: You see a lot of patients with hemophilia.

Robert F. Sidonio Jr., MD, MSc: Yes.

Peter L. Salgo, MD: What are the signs and symptoms that you commonly see in your patients?

Robert F. Sidonio Jr., MD, MSc: It depends on the severity. In hemophilia, there are multiple severity sites. Patients who have factor levels of less than 1% are called severe; 1% to 5% are called moderate; and 6% to 50% are called mild. When you look at the general presentation, mild patients can present much later. Sometimes, you can see them in the early teen years or in their first couple years of life, maybe in a hemostatic challenge like a surgery, a tonsillectomy. Sometimes, that’s not the way we would like to diagnose them, but oftentimes that is.

Peter L. Salgo, MD: You get a call from the OR [operating room], “What’s going on here?”

Robert F. Sidonio Jr., MD, MSc: Yes. The surgeon is telling you he won’t stop bleeding, and that’s when we get the phone call. Typically, the more severe and moderate patients present much earlier. For example, just this week we had a severe hemophiliac present and he presented the classic way, which was circumcision bleeding.

Peter L. Salgo, MD: Really?

Transcript edited for clarity.

Robert F. Sidonio Jr., MD, MSc: Sometimes, we make the diagnosis in the first few days of life. Oftentimes, there’s not much bleeding in the beginning, but it’s when they go home and continue to ooze. That’s a very classic presentation. Sometimes, it can be severe, like intracranial hemorrhage or oral bleeding that won’t stop.

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