An Overview of the Hemophilia Treatment Paradigm
A panel of experts come together to review the historic understandings of hemophilia, opening the discussion to how it is approached and managed today.
Peter L. Salgo, MD: Welcome to this Specialty Pharmacy Times® Peer Exchange discussion. Today, we’re going to discuss hemophilia. Hemophilia is a rare disorder in which the blood doesn’t clot normally due to insufficient blood-clotting proteins or clotting factors. The most common types are hemophilia A, with a factor VIII deficiency; and hemophilia B, with a factor IX deficiency. A person with hemophilia may bleed for a longer time after an injury than a person without hemophilia. That person would clot normally. The concern is with deep bleeding inside the body—such as in the joints, the knees, the elbows, or the ankles—that can cause tissue and organ damage and bleeding in the head that can cause serious neurologic injury. Throughout this discussion, my colleagues and I will take a look at the recent advances in therapeutic options for the management of hemophilia.
I’m Dr. Peter Salgo, and I’m a professor of medicine and anesthesiology at Columbia University College of Physicians and Surgeons and an associate director of surgical intensive care at New York-Presbyterian Hospital.
Participating today on our distinguished panel are Tim Boonstra, pharmacist and pharmacist site manager of Fairview Pharmacy Center for Bleeding and Clotting Disorders in Minneapolis, Minnesota; Lacey Chapman, pharmacy manager of Factor One Source FAST Pharmacy and PRN pharmacist at Johns Hopkins Bayview Medical Center in Baltimore, Maryland; and Dr. Robert Sidonio Jr., assistant professor of pediatrics and associate director of hemostasis and thrombosis at Emory University School of Medicine in Atlanta, Georgia and Children’s Healthcare of Atlanta.
I want to thank you all so much for being with us. Why don’t we get right down to it? This is a fascinating discussion. Why don’t we start with some basic definitions? I want to know, our audience would like to know, your definitions of and the differences between hemophilia A, hemophilia B, and Von Willebrand disease. Where do we go with this?
Robert F. Sidonio Jr, MD: We can start with the most common bleeding disorder, Von Willebrand disease, and that’s a defective Von Willebrand factor. That’s as common as 1 in 1,000. In some studies, it might be as common as 1 in 100 with very, very mild reduction. It affects both men and women and it’s typically autosomal dominant, with some rare cases being autosomal recessive. And then, there are the more commonly known hemophilia A and B. We use the terms factor VIII deficiency for hemophilia A, and there are 3 main severities for that. About 1 in 5,000 males have that. These are X-linked disorders. Hemophilia B is much less common, about 1 in 25,000 males, and that’s defective factor.
Peter L. Salgo, MD: Now, hemophilia B is called Christmas disease.
Robert F. Sidonio Jr, MD: Yes.
Peter L. Salgo, MD: I’ve got to ask because I forgot: Why?
Robert F. Sidonio Jr, MD: It’s named after the first patient. It wasn’t the first patient who was diagnosed, but the first one who was described in literature. It was named after that family. It is actually, when you look back, the royal disease label that’s often put with hemophilia. When you look back—and they’ve actually traced this—Queen Victoria was a hemophilia B carrier. We all know that history of how that spread throughout Europe and actually changed history.
Peter L. Salgo, MD: It did. In fact, we always talked about this, at least in medical school. The czars who were genetically linked to the royal families elsewhere, the male offspring, often had this. But I didn’t know that it wasn’t factor VIII, it was factor IX.
Robert F. Sidonio Jr, MD: It was a factor IX deficiency. They went back and traced this. It was interesting how when you look at those same czars and the czarevitches, their doctor was actually Dr. Grigori Rasputin. He probably helped them the most by not doing anything because some of the interventions at that time were probably harmful for those people.
Peter L. Salgo, MD: The other thing I think you mentioned—and if not, let’s bring it up—is that there’s a spontaneous mutation rate.
Robert F. Sidonio Jr, MD: Yes, In Von Willebrand disease, we don’t know exactly what that rate is. It’s probably less common than in hemophilia. But in hemophilia A and B, the spontaneous rate is about 30%. Oftentimes, there’s no family history, which makes it very difficult when you’re dealing with a patient who’s bleeding, and you don’t know why because there’s nothing to trace back to that.
Peter L. Salgo, MD: The reason I ask is—let’s go back in history—after the Russian Revolution and the czars were gone, hemophilia didn’t disappear in Russia.
Robert F. Sidonio Jr, MD: It did not, and it’s been around since people recorded this. We’ve talked about this. It’s recorded in the Talmud. It mentions hemophilia. It doesn’t mention it by name, but it mentions a bleeding condition and it talks about not circumcising the second child after one dies. You have to have at least 1 or 2 children die, but it talks about how the mother’s sister’s sons don’t have to be circumcised as well. And so, they obviously understood how it was transmitted. They understood something was there, they just didn’t have a name for it.
Peter L. Salgo, MD: Wow. It’s always fascinating to go back to the ancient literature. They knew about this. They didn’t know about X and Y chromosomes, but they knew transmission before Mendel.
Robert F. Sidonio Jr, MD: Yes, I know. It’s pretty amazing. Von Willebrand disease was one of the ones that was actually named after the founder, Erik Adolf von Willebrand, and he discovered this in a tiny little island, the Åland Islands. The first case was a little girl named Hjördis who had devastating bleeding events. They initially called it pseudo-hemophilia because they were seeing this in girls and they didn’t understand why. Unfortunately, that girl died after her fourth period. And so, it wasn’t until a couple decades later before they figured it out.
Peter L. Salgo, MD: Well, let’s talk about the genetic predispositions leading to hemophilia. We’ve got the prevalence of hemophilia A, B, and Von Willebrand disease. What does that look like?
Tim Boonstra, RPh: Well, there are about 20,000 patients with hemophilia currently in the United States. For Von Willebrand disease, it probably affects about 0.5% of the population.
Peter L. Salgo, MD: That’s not small.
Tim Boonstra, RPh: No, but there are varying degrees of severity. There’s type 1, type 2, and type 3; depending on what type you have, you may or may not need treatment.
Peter L. Salgo, MD: What about hemophilia A and B, what’s the prevalence of those?
Tim Boonstra, RPh: Generally, 80% of patients with hemophilia will have type A, and then 20% will have hemophilia B.
Peter L. Salgo, MD: Let’s talk about the mortality rates, treated and untreated. If you leave this alone—if you are Rasputin, and you don’t do anything—what’s the mortality rate for each of these, A, B, and Von Willebrand?
Tim Boonstra, RPh: I don’t really like to go to mortality rates, necessarily. If it’s untreated, there is certainly some serious morbidity involved with that. But it certainly has changed over the years.
Peter L. Salgo, MD: Tell me about that.
Tim Boonstra, RPh: There were not very effective treatments early on in the 60s and 70s, not very good treatment. And then in the 80s, of course, there were the dark days of hemophilia with the bad blood supply, where we had an HIV epidemic. And hepatitis C was during that time.
Peter L. Salgo, MD: I was practicing during that era, and I recall the entire hemophilia population of the United States being wiped out. It was the most tragic thing.
Tim Boonstra, RPh: Yes, they certainly were very dark days. But now, when in the 80s we were able to get rid of those viruses from the blood supply, viral transmission is virtually unknown.