Amanda Wilde (Host): Meaningful Medicine is a Novant Health Podcast bringing you access to leading doctors who answer questions they wish you would ask. From routine care to rare conditions, our physicians offer tips to navigate medical decisions and build a healthier future. I'm Amanda Wilde, your host. And in this episode, we'll look at signs, symptoms, and the latest advancements in treatments of pediatric sickle cell disease. Pediatric hematology oncologist, Dr. Felipe Bautista, is here to break it down. And Dr. Bautista, welcome to the podcast. Thank you so much for being here.

Felipe Bautista, MD: Thank you so much for the invitation.

Host: To begin with, can you explain what sickle cell disease is and how it presents specifically in children?

Felipe Bautista, MD: Yes, of course. Sickle cell is an inherited blood disorder. It's congenital that is a small genetic change in the hemoglobin. The hemoglobin is a protein that we all have that carries oxygen around our bodies inside the red blood cell. So, nowadays, it is diagnosed on newborn screen. In the United States, every state screens for this at birth, so we get to diagnose it as soon as a baby is born.

Now, this disease can affect any organ in the body. You know, that change in the genetic code of the hemoglobin causes that hemoglobin to, like—we call it polymerization, meaning it kind of like it sticks together. It makes that red blood cell abnormal, like kind of half moon, crescent shape, sickle cell shape. And it causes other downline changes in the biology of things, which increases inflammation, the stickiness of things. The immune system is also involved and it leads to problems pretty much in any organ in the body, you know, and as time goes by, that can get worse.

So, in children, as compared to adults, obviously, you're just kind of born with it, right? And at the beginning, your body is protected by hemoglobin F, fetal hemoglobin that we all have, has no sickle cells in it. That's the vast majority of hemoglobin at birth. So, we don't see symptoms right away. But of course, you have a family That has a baby with this chronic blood disorder. So, a lot that goes into that at the beginning as compared to obviously an adult where it's the actual patient being diagnosed and things like that.

Host: So, there's screening from birth, but you just mentioned there maybe no symptoms right away, but what symptoms or complications should parents be aware of in younger kids?

Felipe Bautista, MD: So, again, it takes about four or six months for the hemoglobin S or the sickle hemoglobin to be the most abundant in the body, right? So during those first few months of life, kids are relatively protected. But the changes that start to happen little by little, also right away.

So, one of the first things that occurs is that the spleen, the spleen is an organ that we all have. It is a filter for blood, it starts to trap those sickle cells. The sickle cells get stuck in the circulation in there. And the spleen slowly stops working very well, little by little, right? So, the spleen in all of us protects us against some infections, some important bacterial infections that can make us very sick and can be life-threatening.

So, the first thing that we're always trying to make families aware of that we're on the lookout for is severe infections with what we call encapsulated bacteria. So, these things can present with sepsis, bloodstream infections, meningitis, things like that. So, one of the most important things to make families aware of or to understand is that there's an increased risk of some infections that can be life-threatening.

So at any point in the lifetime of a patient with sickle cell throughout their entire life, if they have a high fever, they always need to be evaluated right away. And that's something that even some physicians or some healthcare providers are not aware of, and we still recommend that, they need to be evaluated right away and go through a workup, make sure that there's no bloodstream, life-threatening infection and get treatment like that.

I would say the initial maybe more emphasis that we place on a potential early symptom that we see—but, of course, the most common symptom in sickle cell, most people know about this, is pain crisis, right? So, those sickle cells get stuck in the circulation, decrease blood flow to different areas of the body, of course, your bones. And it's more complicated than that. There's inflammation. There's other things that go on. But in general, pain crisis is the most common symptom.

And in babies, while the other things that we can see are like swelling of the hands and the feet, we call it dactylitis. And then, there's, again, inflammation. That's the way that a pain crisis may present in a little baby. But overall, the pain crisis, again, where is the pain? Pain can be anywhere actually. That's another thing that we're on the lookout for early on.

Host: And what treatments or management strategies are currently available for pediatric sickle cell disease?

Felipe Bautista, MD: So, the field is undergoing an exciting time in the sense that there's more research than in the past. For a long time, this disease does not occur with other similar chronic illnesses that maybe affect more people, in terms of research and things like that. This affects minority populations. Those differences in the healthcare system for minority groups are well-evidenced in this disease, unfortunately. And for a long time, we've made progress in that. So, it's an exciting time in the sense that there's more research, newer therapies that are coming in. And we may address those in a little bit. But traditionally, we've had blood transfusions to help manage some of the symptoms. Of course, that comes with a big burden to the family, lots of other potential side effects from blood transfusions. And it is only, like, we try to use it more only on the acute issues and things like that.

But there's a medication, most people are aware of this, hydroxyurea that has been used in sickle cell since the 1970s, 1980s. And it still remains our best outpatient therapy. Even after all these decades, it still remains our main, least aggressive disease-modifying. medication. And it actually can be very helpful in most patients.

You know, it's tricky in sickle cell because there are different types of sickle cell. And we think of the different types, there's still a lot of variation within patients. So, not everybody responds very well to hydroxyurea, but most people do, especially the ones with severe forms of sickle cell. So, hydroxyurea has been shown during these decades to prolong life—so, extend the life in patients with severe forms of sickle cell. Imagine these are medications that can make these patients live longer.

So, that's something that we found with research along all these decades. So, that's still very good. It helps by protecting damage from sickle cell to the different organs in the body. And the downside is that, as a medication, they have to take every single day for essentially the rest of your life, unless you're undergoing other disease-modifying or curative transformative therapies, right? So, that's a big burden on the patients. And again, not everybody responds even if they take it every day, but most people do have a benefit, right? It's not a hundred percent effective, but it helps to decrease essentially most complications from sickle cell. Maybe not all, but most complications, including those pain crisis.

Host: Along with that, early and consistent care can make a difference in a child's long-term health and quality of life. How have you seen that play out?

Felipe Bautista, MD: So, in pediatrics, we first start dealing with the parents, with the family, actually, throughout most of our time than the the patients, right? So, there's lot of education that needs to go on, and establishing that trust that is so important in healthcare with the patients family, right?

So, a baby, imagine that it's just a baby, right? It's just there. And we're sharing all these risks that the disease can carry, affect any organ in the body and things like that. So just, having a connection with the family is very important. So, a lot of our efforts go there in education, trying for the families to understand the risks of the disease. That can be very overwhelming. How to navigate the healthcare system, how to understand what needs to go in, a lot of prevention. A lot of prevention, prevention, prevention is what we do mostly on our outpatient visits.

And a lot of families have a hard time understanding that or keeping up with the multiple appointments that are required. So at the beginning, it is really, again, getting to have that connection with the family, understanding education, what things to look out for and things like that. And also, a big component of this is genetic counseling. Some of these families never had a member of their families with sickle cell disease. And suddenly, they have a baby with a severe form of sickle cell disease. What does that mean? So, having the parents understand where it came from, the risks, even if there's no family members that were affected, how do you navigate all of that? What does it mean for family planning in the future?

So, our goal is not to make decisions or say what do you or should not do, but you know, educate parents with the tools that are there to make decisions for themselves. So for example, you know, you have a child with severe form of sickle cell disease, you plan to have more children in the future. My goal is for people to understand that there are things available out there. You know, there's things like in vitro fertilization that you can pursue to prevent having a child from sickle cell, but that's their decision. It's not that they should or should not do that, but most people are not aware that that is even an option, right?

To people with who are carriers for sickle cell, you know, it typically is about a 25% chance of having a child with sickle cell. So, that also means for a family that is a 75% chance of not having a child with sickle cell. So, how do you navigate those decisions? You know, our goal is to empower families to be armed with the knowledge, to make decisions for themselves.

And later on, as the children continue to grow, right, they start to venture into the early teenage years or sometimes we forget that we did all this teaching with the parents, but we now have to translate that and communicate it in an easy way to the patient, as they keep growing as a teenager and prepare them to be empowered on their own because their parents are not going to be there holding hands, you know, like forever. And the healthcare system also, it's not as welcoming or as helpful in this regard. You have to be empowered to really kind of keep going on your own, right? So, all of those are the challenges of pediatric sickle cell care, but we try to do our best.

Host: That's interesting. I was just going to ask what comprehensive care that addresses pain management, to school support, to mental and emotional health look like, not just for children themselves, but for families?

Felipe Bautista, MD: Yeah, I know. Very good question. So, it takes a village to provide the best care possible for individuals with sickle cell and multiple levels, right? So important to start early, right, with an expert in sickle cell who at least, you know, is involved some regards. Some areas of the country don't have access to a pediatric hematologist near home. So, primary care physicians can play key role also in managing a lot of the things from sickle cell. But having an expert who's at least guiding every few months. And fortunately, here in Charlotte, here in our network, we do have a comprehensive sickle cell center who has the expertise to explain, they do the education, things to look out for and start treatments early. So, we start the hydroxyurea at nine months of age in individuals with severe forms of sickle cell. The milder forms, again, a lot of patients do well with the milder forms without a lot of complications, especially during childhood. And we do follow them a little bit less often, still very closely, but a little bit less often as they're less likely to run into a lot of complications early on.

But a comprehensive treatment for children involves multiple things, right? So, not only the education piece, which we actually have, for example, a dedicated sickle cell nurse who has her own curriculum and kind of tracks how much progress we have made with each family. So, that's great to have the luxury of somebody else—not just the physician or the nurse practitioner or the provider—trying tog to do it alland kind of track these changes, right?

We have medications, again, the use of hydroxyurea. And then vaccines. I didn't talk about vaccines, but they've been so important, so important to prevent the infectious complications from sickle cell. You know, we see now much less often those sepsis or things that my mentors used to see and those deaths from infectious complications. Not that they don't happen, but they are much, much more rare is because of vaccines. So, we are really like, "Hey, we got to go on with such an important part of the preventative care."

And the recommendations for vaccine can be a little bit complicated. So, they keep updating every time and staying on top of that also requires a little bit of extra effort from providers and, again, where the expertise comes in, but we are fortunate to be able to administer those extra vaccines or those extra doses or boosters here in our office too. So again, the comprehensive care, not only the specialist, but being able to provide some of these extra things so that the family doesn't need to have another appointment with somebody else to get some of these extra interventions that are necessary.

Another key important component of sickle cell is the screening for things like stroke. So, sickle cell is one of the most common reasons for a stroke in pediatrics. And in general, patients with sickle cell in the adult years that at increased risk of stroke, right? So, very important complication to try to prevent, keep an eye on. So, have the ability to do some of the screening tests that we do to try to prevent, catch it early, things like that. So, for example, there's ultrasounds of the head called transcranial ultrasounds that are done to screen for the risks of stroke within the sickle cell population that is already at increased risk.

It's also recommended to do MRIs at school age years to screen for silent strokes, you know, there are smaller lesions that may not be a full-blown stroke, but have big implication for the lifetime of the patient, that can create neuropsychological symptoms, learning difficulties, increased risk of stroke farther down the line. So, all of those things are embedded and how to apply them is challenging sometimes. But we have the ability to do that. Continue with that.

Then, we do screenings for cognitive development, the learning difficulties. We started doing that not too long ago with the help of one of our neuropsychologists that we have available here in the network. We have the luxury of having that. That's not available everywhere. And to further kind of identify those kids who are already having some issues, right? Support them, make sure that we are addressing them. Brain imaging to see if it's related or not, the sickle cell support, and kind of set them up for success in the future.

And the other thing, part of the comprehensive care here ideally would be the psychiatric psychological part. Sometimes chronic pain is a big problem. Very challenging to treat in some of our patients, usually when you get into more like the teen years. Not everybody, but some patients get into this chronic pain cycle that is so difficult to get out of. And it needs expertise from multiple specialties. But that's something that, ideally, every comprehensive sickle cell center should have. And it is also, again, a luxury, right? Having a psychologist in the clinic who sees the patients, you know, at the same time of the regular visits, who's an expert in pain, right? I mean, that's again, some of the things that will be ideal. And we don't have it at the moment, but we continue to work with the outpatient services within our network or outside of it.

And finally, not to get too long on the days, but the best comprehensive care for these patients will be like a lifelong center for sickle cell, like the ones that care for the lifespan, right? and there are some centers in our country that do that. And what that means is really your same sickle cell expert seeing you from birth until the end-of-life. So, your whole life, your same team, your same provider, your same doctors, same nurse practitioners, same nurses at the same center, at the same physical clinic—that's, again, a dream here. You know, we have our adult colleagues who also help us and we are trying to work with what we have. But it's difficult to accomplish that. But that will be ideal for this chronic illness. And there are some centers who are doing that.

Host: You have described a sophisticated set of tools and systems for addressing this disease in all of its facets. You also mentioned there are new therapies and research developments on the horizon. What are those and are there any curative options that give you particular hope for the future?

Felipe Bautista, MD: Yes. Like I said earlier, it's an exciting time for sickle cell in the sense that there is more research, there is more advancements that are actually happening very quickly, and how to implement them is still very difficult.

So first, well, for a long time, we had a cure for sickle cell. But that cure, it's the stem cell transplant or bone marrow transplant is another term for that. That has been available since the 1980s. When we first realized that it cures sickle cell by chance, you know, somebody with leukemia had a bone marrow transplant and cured the leukemia and also the sickle cell, right?

But anyway, that process is very complicated. It involves chemotherapy, knocking down your immune system, very high-risk of complications like graft-versus-host disease and things like that. And while things have gotten much better, and we are making progress in that field as well, there's high-risk of complications. So, the cost of cure, it can be pretty high too, right?

Now, the field has made advancements in the sense that for patients who have a full sibling who is a full match for something like a curative therapy like a stem cell transplant, you know, again, the outcomes are improving and we're getting better at that. So, that's something that certainly we offer or we talk about, right? Again, we arm the families, the patients with knowledge to make decisions for themselves. But if a patient has a full match sibling and has severe forms of sickle cell disease, we do encourage a referral to a transplant center to talk about this curative therapy.

Now, newer therapies out there as a lot of people have heard, have been on a New York Times, a lot in the press and things like that, and different news outlets is gene therapy or gene editing, some other word for that. And it was FDA approved a couple years ago Commercially available for kids and adults—kids older than 12 years of age and adults. It's a very promising treatment, already giving us more hope, already transforming the disease in a lot of patients, but a lot of challenges remain.

So. I'm hopeful and I'm excited that this will keep going, and we will get to a place where it's more accessible, more affordable, not only here in the United States, but in the entire world where most of the patients with sickle cell live. And a lot of challenge remain. But again, it's an exciting time, right? It is very expensive And still, we're trying to work out who is the best candidate for that, how to pay for it, and how do we speed things up a little bit. But it's very promising. So, I am overall very excited about the future for the options that we'll have to cure or transform the disease in our patients.

Host: Well, with all of this happening, I can imagine parents may easily feel overwhelmed by the diagnosis of pediatric sickle cell disease. I just want to end by asking what guidance or reassurance would you most want those parents to hear?

Felipe Bautista, MD: Yeah, the first thing, I mentioned it before too, but it's establishing that trust, having the family and the patient trust the providers who are taking care of them, the specialists who are taking care of them. It's so, so important.

And, again, the healthcare system has had some barriers. It still has a lot of barriers for minority populations including the patients who are most affected with these condition, african Americans, Hispanics, minority populations from other parts of the world. That has made it very challenging. Our trial record with some research, we think sickle cell is also tricky to navigate. So, try to relay and establish the trust so that, you know, we can have honest and helpful conversations is so, so important. And I would say, trust your medical team. We're here to help in the best way we can, talk to you, inform and arm you with knowledge.

And then, talking about this new gene therapy, gene editing. It's an exciting time. It gives me a lot of hope already. More tools that I can offer my patients already. Some of our patients are going through these treatments as we speak, which is very exciting. And before, we only had the transfusions, hydroxyurea, and not that much more to offer. But again, patients, families with knowledge to make decisions for themselves. That's the thing. But hopefully, better days are coming for sickle cell.

Host: It's evolving. Well, Dr. Felipe Bautista, thank you so much for this Conversation And for sharing your expertise and insights today into pediatric sickle cell disease.

Felipe Bautista, MD: I appreciate the opportunity to talk about this disease, and thank you very much.

Host: To find a physician, visit novanthealth.org. For more health and wellness information from our experts, visit healthyheadlines.org. This is Meaningful Medicine, a Novant Health podcast.