Children’s Hospital of Philadelphia hematology clinical manager, Regina Butler, RN, talks about a new treatment for hemophilia.
Interview conducted by Ivanhoe Broadcast News in 2023.
Can you explain what hemophilia is?
Butler: Yes, hemophilia is either the deficiency or the absence of one of the proteins that we need to clot our blood. We have a lot of factors in our blood that use- that contribute to clotting. The most common deficiency causing hemophilia is the deficiency of Factor VIII or the deficiency of Factor IX.
Can you explain what causes it?
Butler: Yes, hemophilia is genetic. So it’s inherited, it’s caused by mutation on the X chromosome. So we call it an X linked recessive disorder, which is why it’s usually affects males much more frequently than females. Because males have one X chromosome and females have two. So the other one usually compensates for the lack of the affected X chromosome.
Who is at most risk? What do these patients experience, the patients with hemophilia?
Butler: So the most common experience in patients with hemophilia overall, is bleeding into the joints. So the bleeding into the joints can lead to deformity, pain, and disability because the more often bleeding occurs into the joints, the more damage there is to a joint. But bleeding can occur anywhere that we have blood vessels so in children-the most common in young children, the most common is mouth bleeding or head trauma, and then after that it’s joint and muscle bleeding.
And what life do these patients live? Do they have to be careful with what type of activities they participate in and etc because of the potential of bleeding?
Butler: Yes, there have been a lot of changes in hemophilia and how it affects individuals over the last 50 or 60 years. So right now, children that are born with hemophilia do have some restrictions in their activities, but because of the advances in treatment, they leave very full lives and are able to participate in most activities and even most sports. Maybe just not the most high contact sports.
And with the evolution of treatment, before the evolution, I guess what was the prognosis of those patients? What was very limited to what patients of this time?
Butler: Yes, so when I started 50 years ago, most of the patients with hemophilia had some deformity or disability. Some were in wheelchair, some wore braces, some were in crutches. And there was an early death for some of them, it wasn’t really a death sentence, they just often lived limited lives. And now, that isn’t the case at all. Now, very few of our children have any joint damage or even very frequent joint bleeds anymore because of the treatments available today.
Could you tell us about the treatments then and now?
Butler: Sure, when I first started, children with Factor IX deficiency had to be treated with fresh rosen plasma, which is like a transfusion. You hang the bag and it takes a while to infuse. And most of the time it was done in the emergency department or in the hospital. Children with a Factor VIII deficiency used something called cryoprecipitate, which is also a blood product or in the very early days of my time here, some started to use Factor VIII concentrates. So that is the concentrated form that comes in a bottle that was kept in the refrigerator. The unfortunate part about that was that it contained the donators- up to 10,000 donors per lot of Factor VIII concentrate. Which led to the HIV epidemic in the ’70s and ’80s in the United States. Because many- with that many donors and with HIV in the blood products, it was- we were not able to detect it. There wasn’t a test for it, and there wasn’t any way to prevent it.
Fast forward, decades later, how has the treatment evolved?
Butler: The treatment has evolved so rapidly that we sometimes call it new product fatigue. We kept getting better and better products- products Factor VIII and Factor IX concentrates that were purified to prevent infection. Then products that were not derived from any human or animal protein at all to really almost eliminate those risks. And now we have products that don’t replace the factor. But mimic the action of the factor so that they don’t need to get factor concentrate. At least for Factor VIII deficiency. So patients like the warts with Factor VIII deficiency can use a product that they, instead of getting an IV infusion every other day or three times a week, they can take this subcutaneous little needle every two weeks, every three weeks or every four weeks, and prevent most bleeding.
That’s incredible, and can you talk a little bit about now that there’s a potential cure for hemophilia which in therapy? What’s that for? You’ve been treating these patients for over 50 years and be able to see that, that we would potentially have a cure.
Butler: It’s remarkable to me. I feel like I’ve come full circle in my career with hemophilia, starting with very limited treatments and very disabled patients, and ending my career on such a positive note with the potential for a cure in the future. Right now, there are two licensed gene therapy products in the United States. One for Factor VIII deficiency and one for Factor IX deficiency. Of course, we work with children and none of these are licensed for children. And it’s early days, a very few people have been treated with these products so far. But I think it’s just the beginning, there are a lot of products and clinical trials and I think that there, if not a cure for at least, turning severe hemophilia into mild hemophilia and decreasing the treatment burden and limiting the lifestyle disruption for the families is really on the horizon.
And what’s the life expectancy for patients 50 years ago then and now?
Butler: I think, when I started, the life expectancy was somewhere in the 30s. And then it increased. Then it actually went up to the ’60s or ’70s with the treatments that we were able to provide. And then of course, it dropped significantly during the tragedy of HIV. And now I think it’s back up to normal or near normal.
Can you tell them a little bit about the Ward family? This has been in their family for a while now, right?
Butler: Yes. When I started, one of the first families I met was Melody Ward’s father- grandfather rather, and grandmother. And her- so they had- so Melody’s grandmother and grandfather had five children, I believe, but three of them were boys and all three boys had hemophilia. And so they had very significant bleeding, lots of trips to the hospital, spent a lot of time in the hospital. Her father had more significant complications than his two brothers. Unfortunately, they were all affected by the HIV epidemic. And her father actually lived to be, I think, 52 or somewhere in his ’50s. So her father really lived longer than his brothers, but they had- her grandmother was an amazing woman who was a pioneer and learned how to treat her children at home early on so that she would do the IV infusions for her children at home to help them be able to go to school and participate as much as possible. But they had a lot of limitations and they had- they did suffer pain and frequent hospitalizations and frequent bleeding, and lots of problems with their joints. Whereas then when Melody’s first son was born, we met- I had met Melody as a little girl, but knowing her grandfather and knowing how hemophilia is transmitted, usually from fathers to daughters, who transmitted to their sons. And I met her when she had her- again when she had her first son and was diagnosed- he was diagnosed with hemophilia. And then her second son was diagnosed with hemophilia, but they were such a well-educated family. Even her husband who didn’t grow up with hemophilia, she must have really spoken to him a lot about it because they were very well informed and very eager to do whatever they could to make the life of their children safer, easier, and more normal. And in the beginning, I remember Melody and her husband taking turns bringing their oldest son, Jayden, three times a week to the clinic to get an infusion before they were able to do it themselves. And then they took that responsibility on themselves and their children do very, very well. They’re active and healthy and remarkably happy children. And now they have the even most advanced treatment available to children so that they don’t even need to get three times a week infusions, they get the Sub-Q injection.
How is their son’s treatment different from what others have had like Melody’s dad?
Butler: So it’s remarkably different. The treatment is so much different in that, the early days, when we had to use IV infusions for factor replacement, first, we didn’t even treat prophylactically, we just treated children that had bleeding. When they had bleeds, they got treated. And then the advances were to treat preventively, try to treat several times a week to prevent bleeding, which was a tremendous change. And that really significantly changed the trajectory and the lives of individuals with hemophilia, especially children. So her father didn’t have prophylaxis, her uncles didn’t have prophylaxis. So even in the beginning, her boys had the best care and prophylaxis, and parents that really made sure that that happened regularly. But their fathers, also when you have- when you’re using factory replacement products, which was the traditional treatment, you need to get- you need to access a vein. So many children had to have central venous access devices implanted, which come with their own set of complications and trials and tribulations. Or they needed to find parents or home care nurses who could actually insert the needle into the vein or to bring their child to clinic several times a week. So now, all of that disruption in their family life and that pain and those risks have really are avoided with the treatment that Melody’s children have now.
Can we talk about bioengineer protein therapy? What is it and how does it work? Is that- I think that is meant for gene therapy. Do you expect life to be very different for the boys as they grow older?
Butler: Yeah, I think for the Ward family, I think those boys will have a near-normal life. They always need to remember that they have hemophilia, so that if they have to have a procedure or a surgery, or they’re in an accident, they need to be careful and they need to make sure that they have Factor VIII on hand to replace it if they bleed. But for the most part in their everyday life, I think that they will have a very similar life to the other children that are in their class.
And what do you think is the most exciting research? You talked about gene therapy, but is there anything in the pipeline for hemophilia?
Butler: I’m a little bit excited about some new therapies on the pipeline for Factor IX deficiency because right now those children with Factor IX deficiency and of course adults need to infuse once a week or even some of the products once every two weeks, but they still have to have IV infusions. There is no current product to treat Factor IX deficiency as easily as we have for Factor VIII. So I’m looking forward to advances for those patients.
In the Ward family, they have Factor VIII?
Butler: They have Factor VIII.
Got it. Anything else you’d like to add or that we missed?
Butler: No, well, I would like to say that I think that taking care of a child with hemophilia is a team effort. And so the Wards were great members of the team. We like to call the patients and families the quarterbacks or the captains of the team. But it requires the support of a wide range of people. From physicians, nurses, social workers, physical therapists in the healthcare setting, as well as the support of family and friends and other patients with bleeding disorders in the community that provide support to one another.
END OF INTERVIEW
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