Advances and MASAC Guideline Recommendations for the Treatment of Hemophilia - Episode 3
Peter L. Salgo, MD: What are the goals of therapy when you work out a treatment plan?
Robert F. Sidonio Jr., MD, MSc: They’re different for different severity types. For mild and moderate hemophilia, the standard is on-demand therapy because those patients tend to not have spontaneous bleeds. But there are clearly patients who are different, and it goes back to the mutation type. About a third of the moderate patients with levels of 1% to 5% are on regular preventive treatment. But the standard of care in severe hemophilia is prophylaxis. That means regular factor concentrate infusions to prevent bleeding.
Peter L. Salgo, MD: I want to make this very clear.
Robert F. Sidonio Jr., MD, MSc: Sure.
Peter L. Salgo, MD: There are 2 treatments here. One is that they’re bleeding, so let’s stop it. The other is, how about they don’t bleed at all?
Robert F. Sidonio Jr., MD, MSc: Exactly. For severe levels, we want both of those goals, right? We are trying to prevent as much bleeding as we can, but kids fall and they trip and they hit their heads. And then, you still need to treat for acute bleeding events. But in general, most of the guidelines recommend, before age 3 and before the first joint bleed, to start these regular factor infusions. But as you know, starting an IV [intravenous therapy] in a 2-year-old is not a simple task. Just think about it. You get up in the morning and you’re trying to get your kids ready for school. They might have to do some pushups and get their veins ready; you get them warmed up. You’ve got to start an IV infusion factor, and then get them ready for school. You can imagine doing that 3 times a week, 4 times a week.
Peter L. Salgo, MD: That’s a lot of impact.
Robert F. Sidonio Jr., MD, MSc: It’s tough on the kids. And if you can’t get it, the kids get really upset, and obviously it’s very traumatizing.
Peter L. Salgo, MD: There’s something now called hemophilia treatment centers.
Christopher E. Walsh, MD, PhD: Yes.
Peter L. Salgo, MD: How does that fit this whole model of preventing bleeding, and how do they fit in with what you do?
Christopher E. Walsh, MD, PhD: As another historical vignette, back in the 1970s companies were able to purify factor out of plasma. They could draw this down, analyze it, put it in a vial, and ship it to anybody who needed it. You could reconstitute it and infuse it intravenously. Patients were then freed from going to the hospital. They would get these products. They would learn to infuse themselves intravenously and do this at home.
Peter L. Salgo, MD: Again, it’s IV; not IM [intramuscular], not subcutaneously.
Christopher E. Walsh, MD, PhD: IV. That really prompted a whole wave through the federal government of starting comprehensive treatment centers.
Peter L. Salgo, MD: Let me stop you because I’m a little confused. If you can give somebody this drug to administer to him or herself, or with their parents, what do you need a treatment center for?
Christopher E. Walsh, MD, PhD: It’s easier said than done. Diagnoses need to be made. Patients still bleed on this treatment. The difficulty with taking these proteins is they have a short half-life, which means when you infuse it, after a period of hours a lot of it is gone and has to be readministered. It’s very difficult, especially in children but even in adults, to train them to do that. They will still have bleeding episodes while they’re getting treatment.
Peter L. Salgo, MD: Let’s define it. What is an HTC, a hemophilia treatment center?
Christopher E. Walsh, MD, PhD: By definition, this is a grant-based mechanism from the federal government. The group is HRSA [Health Resources and Services Administration] at HHS [Department of Health and Human Services], and if you’re an institution that has a grant mechanism with them, you are designated as an HTC. But this requires you to have nursing, physical therapists, and social workers. Physicians actually are not mandated in this, which is interesting. It allows these groups, which are scattered—I believe there are 130 or so now in the United States—to obtain factor and dispense it to their patients.
Peter L. Salgo, MD: For the average person with hemophilia, if there is such a thing, are these HTCs easy to get to? Are they accessible?
Christopher E. Walsh, MD, PhD: Throughout the United States, they’re obviously in all major cities. They tend to be scattered. Patients are scattered where you would expect, throughout the Midwest or the West. But they do exist in all states, and some patients have to take a subway ride for an hour to come to New York at our center. Some have to drive 3 or 4 hours in Iowa or out to Denver, that sort of thing.
Peter L. Salgo, MD: We talked about pharmacologic approaches to this, at least in terms of clotting factors, but there are other things that we do that are associated. I suppose you use them at the HTCs and elsewhere, the nonpharmacologic options and physical therapy. What do these involve?
Christopher E. Walsh, MD, PhD: Despite the factor therapy, which has revolutionized treatment in this fatal disease because no one really lived past their second decade, with the advent of prophylaxis they’re still bleeding. That requires orthopedic help, but we found over decades that with physical therapy, it used to be to let the kids sit with ice and leave them alone. Now, that’s not true at all. Get them up and moving around; doing special exercises helps them tremendously. We even use ultrasound now in the clinics. That has taken over. We can actually use ultrasound to detect problems in particular joints that patients have.
Peter L. Salgo, MD: We have pain management issues.
Christopher E. Walsh, MD, PhD: Pain management is a massive problem. I was reared in this field when opiates were quite common, and quite frankly in my view that added a whole other disease onto a disease. But it was mandated that aspirin or nonsteroidal agents or anything like that should not be used because they have effects on platelets. It was thought they would potentiate bleeding. Now we use these quite routinely in the clinic.
Pain issues, because we are left with a cadre of younger and older patients—especially older men with all this joint arthritis—are now evolving in this field. It hasn’t caught up anywhere to where we’d like it to be. We want to avoid opiates at all cost. We go to pain meetings. There are a lot of drugs such as naltrexone that we’re trying to use in our clinic: drugs for fibromyalgia, seizure drugs, and other modes of treatment.
Peter L. Salgo, MD: It’s tricky.
Christopher E. Walsh, MD, PhD: Right. Basically, you prevent bleeding and you prevent the arthritis; but we haven’t gotten to that point yet.
Peter L. Salgo, MD: That’s obviously the gold standard, right?
Christopher E. Walsh, MD, PhD: Right.
Peter L. Salgo, MD: No bleeding, no joint damage, and no need for pain medication. Everything comes with a cost, whether it’s antiplatelets from the NSAIDS [nonsteroidal anti-inflammatory drugs] or tolerance from the narcotics, it’s tricky. What about dental work? These people do need dental work.
Christopher E. Walsh, MD, PhD: This group of patients, I have to admit, probably have the worst teeth I’ve ever seen. Why that is, I do not know, other than we see them on a routine basis. They constantly need dental work and there are many dentists who will avoid these patients at all cost because they just do not feel comfortable.
Peter L. Salgo, MD: I was going to go there. That may be why they have terrible teeth: The dentists won’t touch them, and when they do, they’re afraid to do something.
Christopher E. Walsh, MD, PhD: At our center, and at most centers, we have dentists who are attuned to these patients. We have methods to get them treated before and after any kind of dental work, so that’s really not much of an issue. That’s another obvious benefit of HTCs.
Transcript edited for clarity.