Overview, Diagnosis, and Complications of Hemophilia

Experts provide an overview including the diagnosis and complications of hemophilia.

Luigi Brunetti, PharmD, MPH: Hemophilia is a rare disorder affecting about 20,000 individuals in the United States. Due to insufficient blood clotting proteins, or blood cllotting factors, the blood does not clot normally. The complications of improper care can be severe. Our expert panel today will provide a thorough understanding and best practices for the treatment of hemophilia.

I am Dr. Luigi Brunetti, an associate professor in the Department of Pharmacy Practice and Administration at the Ernest Mario School of Pharmacy, Rutgers University in Piscataway, New Jersey. Joining me today are Robert Sidonio Jr, MD, the associate director and director of clinical operations and clinical research in the Hemostasis and Thrombosis Program at Children's Healthcare of Atlanta in Atlanta, Georgia; and Giles Slocum, PharmD, an emergency medicine clinical pharmacist specialist and factor stewardship pharmacist at Rush University Medical Center in Chicago, Illinois. Thank you so much for joining us, let's begin.

Before we get into some of the clinical pearls, I think it's important for the audience to understand a general overview of hemophilia. So perhaps Dr. Sidonio I'll address this to you, can you briefly discuss the genetic alterations associated with hemophilia A?

Robert F. Sidonio, Jr, MD: Hemophilia A, just like hemophilia B, is an X-linked recessive disorder. And thus it primarily affects males, and there are some situations in which females may lionize and express the disorder, or if they have Turner syndrome. But primarily it affects males. It affects about 1 in 5000 males in the United States, it doesn't have any racial predilection, and it's much more common than hemophilia B, which is about 1 in 25,000 males.

And so it's really important when people are getting their history that they understand the genetic inheritance pattern, because oftentimes mothers will be carriers. You don't know who's going to have the spontaneous mutation. In about a third of the cases, there may be no family history at all because it may skip generations because it has only unaffected males in it.

Luigi Brunetti, PharmD, MPH: And in terms of diagnosis, when is a diagnosis of hemophilia suspected?

Robert F. Sidonio, Jr, MD: The way hemophilia is diagnosed, ideally it would be nice if all the women were diagnosed as carriers. We would get a notification, we'd do pregenetic counseling, and we'd be prepared for the potential of a male child having hemophilia. And that's important for us to know for discussions about whether the delivery needs to be a C-section in preparation for diagnosis. Ideally, you can actuallly make the diagnosis from the cord, so you actually don't have to stick the child, which is always ideal. You don't want to stick a child who may have a bleeding disorder, even a heel stick could lead to prolonged bleeding.

A certainly, you want to make the diagnosis before a decision about circumcision. That's often unfortunately the way a diagnosis is mafe. Sometimes patients are diagnosed a little bit later if there's no family history. And it's really important for people to understand that there are different severities. In severe hemophilia, they have less than 1% factor VIII. In moderate hemophilia, they have 1% to 5% factor VIII. And in mild hemophilia, they have anywhere between 6% and 50% factor VIII. Even recently at our center, we diagnosed a 10-year-old with mild hemophilia.

He had bleeding symptoms, but they were mostly related to trauma. And so it's important for people to know the different severities and get a good family history. The laboratory way we diagnose this is some people can use a screening partial thromboplastin time [PTT] assay, which isn't good enough to screen for mild disorders in general. And so it's always good to send factor VIII. And if you don't know, it's better to send both factor VIII and factor IX because some families don't know what type of hemophilia they have.

Luigi Brunetti, PharmD, MPH: In terms of complications—Dr. Slocum, this is something I can address to you—often these patients will present to the emergency department. What are some of the complications that you see in patients who have hemophilia A?

Giles Slocum, PharmD: As what was just previously discussed, there's that spectrum of severity, right? So depending on where they are along this continuum of severity, we typically see people coming in with large joint bleeds, muscle bleeds. Those are probably the 2 hallmarks that we see in our own emergency department. Those are the areas that they usually present to.

Luigi Brunetti, PharmD, MPH: And in terms of risk factors, there are many, right? I guess it depends on how active an individual with hemophilia A may be. And then there could be some drug risk factors as well. So that's something maybe I could address to both of you. How do you handle some individuals perhaps with hemophilia A who are older and may use over-the-counter products such as nonsteroidal anti-inflammatory drugs [NSAIDs]? What are your thoughts on that?

Robert F. Sidonio, Jr, MD: In the care of pediatric patients, we pretty much avoid any use of NSAIDs. What's interesting is when we see our adult colleagues, it's not unusual to see them on ibuprofen, for example. There are very limited data on the utilization of that. And in certain circumstances, it's probably relatively safe. But chronic use obviously could lead to adverse effects like gastrointestinal [GI] bleeding and could make their bleeding symptoms worse, particularly in adults who may or may not be on prophylactic factor therapy. I know we're going to talk about that in a little bit.

It's a tough discussion particularly in this day and age, when your'e talking about pain management and we're trying to limit our use of opioids. And we've had some other products that have been removed from the market. It can be challenging. But get a good history on the utilization of those medications and try to replace them, particularly if they have headaches, with medicines that are safer.

Luigi Brunetti, PharmD, MPH: Sure.

Giles Slocum, PharmD: I'd like to pick up that as well. In our patient population, in our electronic health record, sometimes you'll see aspirin and NSAIDs, it's like allergies. And I think it's important to note that if they're not actively bleeding, or depending on the severity of the headaches, if it's not for chronic use, it's something just to piggyback on and say, I think it is probably appropriate and can be tolerated.

Robert F. Sidonio, Jr, MD: Yes.

Luigi Brunetti, PharmD, MPH: And this may be something we circle back to when we talk about treatment goals, because some patients in fact need aspirin, right, or need to be on an antiplatelet agent, and we can talk about how we handle those situations.