Approaching Risk Factors and Diagnosis of Hemophilia


Considering the risk factors and symptoms that might lead one to seek medical attention, expert panelists review the diagnostic workup of hemophilia and query whether or not universal screening is feasible.

Peter L. Salgo, MD: We’re up to date now. Here we are 2018. What do these folks have to look forward to? Is the mortality rate the same as all-comers? Is it slightly higher than all-comers?

Robert F. Sidonio Jr, MD: If you look at some of the studies—and they track this better in Europe than we do in the United States—it’s almost approaching normal healthy males, slightly behind. Obviously, if you have a complication like the inhibitors, and I know we’ll talk a little bit more about that, your mortality rate could be 2 to 3 times higher. But what we’re seeing is that it’s more morbidity issues than mortality. But certainly, in most types of Von Willebrand disease and hemophilia without inhibitors, those patients are often living almost normal lives.

Peter L. Salgo, MD: Let’s talk about the risks and the complications then. What is it about these diseases that affects the population and affects their anticipated lifespan?

Lacey Chapman, RPh: The only thing that I see is people have problems with their joints. People with hemophilia get blood pooling into their joints when they have a bleed, and it just compounds over time. They have joint arthropathy, they have problems with chronic pain, and they even have muscle atrophy. If they have a muscle bleed, that causes problems in the future. It’s also known that they have a higher risk of osteoporosis, so this must have something to do with the interaction of factor VIII with the bone. We could recommend extra calcium and vitamin D supplements for them. And for some reason, they had a higher risk of heart disease in one of the studies that I was reading. So, it’s just within our recommendation that we tell our patients to eat healthy, exercise, and try to decrease their risk.

Peter L. Salgo, MD: It’s funny. We have how many diseases from how many different specialties, and the recommendations always funnel down to eat better, stop smoking, and don’t drink too much. You think that it’s generic, but it’s not.

Robert F. Sidonio Jr, MD: Yes.

Peter L. Salgo, MD: This is how the body works.

Robert F. Sidonio Jr, MD: Sure.

Peter L. Salgo, MD: By the way, regarding the progressive joint disease, I’ll bet that it’s an inflammatory response. Blood does not belong in a joint space.

Robert F. Sidonio Jr, MD: You’re correct. Before we were trying to prevent too many joint bleeds, and now we’re trying to limit the number of joint bleeds because once you set that into motion, it leads to all these downstream inflammatory effects. That joint is never the same, even after 1 bleed. They started doing prophylaxis in the 1950s in Sweden and other countries in Europe, and they followed those same men for 30 or 40 years. What they’re seeing is that we’re delaying joint disease into their 30s and 40s. It doesn’t stop it completely, but hopefully we can delay until much later in life.

Peter L. Salgo, MD: If you get down to zero bleeds, period, the guess would be no joint disease, right?

Robert F. Sidonio Jr, MD: Yes.

Peter L. Salgo, MD: That’s the gold standard.

Robert F. Sidonio Jr, MD: Yes, and we know that there are some of what we call ‘microscopic’ or ‘microbleeds’, that’s a newer topic that we discuss. If you follow the joint range of motion of normal individuals compared to hemophiliacs, even in those milder patients who report never having a joint bleed, the range of motion in their joints goes down faster than a normal person.

Tim Boonstra, RPh: The most important person at our Hemophilia Treatment Center, and our hematologists agree with this statement, is our physical therapist.

Robert F. Sidonio Jr, MD: Definitely.

Tim Boonstra, RPh: They guide a lot of the therapy that takes place at our center.

Peter L. Salgo, MD: I haven’t heard that whole concept of microbleeds before, but it sure makes sense: a little bit here, a little bit there, and it adds up.

Robert F. Sidonio Jr, MD: It adds up. It might not be noticeable, but over time, if you do an MRI, you see these little ditzels in there and cysts that are probably from an old joint bleed.

Peter L. Salgo, MD: Let’s go over diagnosis because if it is—I know the correct term is not ‘variable penetrance’, but variable…

Robert F. Sidonio Jr, MD: Expression, maybe?

Peter L. Salgo, MD: There’s the word. You studied it. Sometimes diagnosing this isn’t necessarily straightforward, or not even done early in life. What are the signs and symptoms you look for, and then how do you work it up?

Robert F. Sidonio Jr, MD: Like Lacey said before, they can often present with life-threatening bleeding events. Obviously, the more severe it is, the more likely you’re going to present earlier in life. But people need to remember that those with mild disease may present when they are 10 or 15 years of age. I saw a patient who developed it after a tonsillectomy. Everybody thought it’s impossible for him to have mild hemophilia, but it isn’t impossible. Typical symptoms are oral bleeding, cuts in the skin that take more than 15 to 20 minutes to stop bleeding, or a nosebleed that goes on for more than 15 to 30 minutes. It’s difficult because we’re not circumcising every child at birth, and that was a typical event that would lead to bleeding. But 20% to 30% of hemophiliacs won’t bleed during a circumcision, and so people get lulled into complacency. But typically, it’s oral bleeding, nasal bleeds, or even life-threatening bleeding events after a bad delivery.

Peter L. Salgo, MD: How do you work this up? If somebody presents with what looks like abnormal bleeding, what tests do you do?

Robert F. Sidonio Jr, MD: The typical tests that we start off with are things like PT [prothrombin time] and PTT [partial thromboplastin time]. When we’re thinking about hemophilia A and B, the part of the pathway would require the PTT test. That would typically be prolonged, but usually the factor level has to be below 30% before you really trigger a prolongation of the PTT. That’s a good start. If there’s any concern, if somebody has a circumcision bleed, I typically send factor VIII, factor IX, and a PTT because I know if it’s prolonged, we don’t want to have to go back and stick a hemophiliac one more time to make a diagnosis.

Tim Boonstra, RPh: Do you see toddlers with bruising coming in when they’re starting to walk, and those things?

Robert F. Sidonio Jr, MD: Yes, exactly. We see these symptoms, and it obviously depends on the mother’s level of concern. Some kids come in and they have 1 bruise and you know that they probably don’t have a bleeding disorder. And then some kids come in with little horns on their heads from so many hematomas, and you know that they obviously have a bleeding disorder. We have to remember in Von Willebrand disease, the PTT is not an appropriate screening test because the factor VIII level is often normal in the vast majority of patients. And so, you have to send those specific tests. With Von Willebrand factor antigen, there are 2 different functional assays: GPIb, or ristocetin; and then of course, factor VIII.

Peter L. Salgo, MD: What I learned is, it’s not just 1 single mutation; this is a wrath of mutations and variable expressions. If they’re having microbleeds, which may not be symptomatic, you don’t want them to have those either. And yet, they’re not going to come to your attention until they’re symptomatic. Why not take every live birth, male and female in the United States, and screen them? What’s wrong with that?

Robert F. Sidonio Jr, MD: It’s interesting you said that. When I was a Fellow in Pittsburgh, that was actually an idea that we had. We said, “Well, how much will that cost? Is that a feasible option?” And it won’t happen until the test gets a lot cheaper. The problem is that intron 22 inversion is the most common and severe. That’s only in 50% of the cases. And so, you’re not going to detect it. It’s not like cystic fibrosis, which has an easy target. That’s the problem. There’s such variety in mutation that it makes that test not feasible.

Related Videos
Related Content
© 2024 MJH Life Sciences

All rights reserved.