Melanie Cole, MS (Host): Welcome to Flourish: a Prisma Health podcast. I'm Melanie Cole. And today, we're talking about managing sickle cell disease. We have a panel for you today, and joining me is Dr. Gary Bell, he's a board-certified internal medicine physician at Prisma Health. And LaChina Moore-Hollis, she's a board-certified family nurse practitioner specializing in Internal Medicine and the care of adults at Prisma Health.

Thank you both so much for joining us today. And Dr. Bell, I'd like to start with you. Can you please let the listeners know what is sickle cell disease, and how is it different when we've heard the term sickle cell anemia so many times? How do they differ, and who is most at risk?

Dr. Gary Bell: Okay. Just as some background, sickle cell disease is the most common inherited red blood cell disorder in the United States, and upwards or over 100,000 people are affected in the United States with sickle cell disease, and South Carolina has the highest rate of sickle cell disease in the US.

And actually, about one in 350 births are affected by sickle cell disease, and one in nine births carry the sickle cell trait. And sickle cell disease itself is somewhat of an umbrella term for a family of blood disorders. And in the US and here in the clinic, we deal mainly with four types.

The most common and perhaps the most severe form of sickle cell disease is the SS disease, where the child or the patient has inherited one sickle gene from each parent. That's the SS disease. The SC, the child inherits one sickle gene from one parent and the C hemoglobin gene from another parent, and they have SC disease, which if you want to say it's a milder form of sickle cell disease, you can.

The other two are sickle beta thal plus, where the child inherits a single S gene, sickle gene from one parent and the beta thalassemia gene from the other parent. And the beta thalassemia sickle cell patient, they're able to make some normal hemoglobin. So, it manifests itself as clinically a milder form of sickle cell disease. Whereas the fourth type of sickle cell disease is the sickle beta-zero thalassemia, where they don't make any normal hemoglobin, and they have a similar clinical picture as the SS disease, and it's more severe.

Thus, with sickle cell anemia, we usually refer to the most severe types, the SS and the sickle beta-zero thalassemia. And you ask yourself, "Well, why is that important?" It's important because we can anticipate how the disease can progress over time, and we can look for the complications that form of sickle cell disease might have. And if you look at, well, what population of patients are at risk for developing sickle cell disease, you know, as background, we do know that the genetic change that occurred with sickle cell disease occur in the areas of Western, Central, and Sub-Saharan Africa, as well as those countries that border the Mediterranean Sea, as well as parts of Central and South America, as well as the subcontinent in Asia, particularly India.

And anyone coming from those areas are at increased risk for developing sickle cell disease. But here in the US, we know that African Americans are particularly disproportionately affected. And we see it more in the African American community, but we are seeing more of a Hispanic population, particularly here in the Southeast, and one in 16,000 births in the Hispanic community can be affected by sickle cell disease.

That's why it's important that everyone is screened at birth regardless of their background, their ethnicity or race. Because early diagnosis means early treatment. And that's just some background in terms of sickle cell disease itself.

Melanie Cole, MS: Thank you so much, Dr. Bell, for giving us that background and really who is most at risk. So China, tell us a little bit about the disease course itself. What symptoms, complications can sickle cell disease cause?

LaChina Hollis: So, sickle cell disease, it can really vary from individual to individual. So, everyone's so different. But it can cause a number of symptoms, and it's really based on the abnormal red blood cells breakdown. So, they break down early and they tend to be sticky, and they stick together and block blood flow, and they cause pain episodes.

And pain is really the hallmark of sickle cell disease. That's the most common symptom that occurs, and that's the symptom that really leads patients to emergency departments. So, pain, really, it's sudden and it can be severe, often in the bones, the back, the chest, abdomen. It can really occur wherever sickle cells clump together and impede blood flow.

Another symptom can be anemia, which can cause fatigue and weakness, dizziness, pale skin, a fast heartbeat. Jaundice is another symptom which can be yellowing of the eyes or skin, and it's a result of the breakdown of red blood cells as well; swelling of the hands and feet, this is particularly common in young children when it occurs; frequent infections particularly in children because the spleen may not be functional. And another symptom is delayed growth or puberty. So, those are just some general symptoms.

Melanie Cole, MS: Well, so China, I'd like you to speak about how some of these challenges change as someone moves from childhood to adulthood. But what I'd also like you to mention, because you mentioned pain as being a hallmark, and if somebody does end up in the ER, what would you like them to know as they become an adult and can advocate for themselves about how to describe what they're going through, how to let the staff know what they're going through so that this can be diagnosed quickly as an episode and be treated for their pain?

LaChina Hollis: Childhood with sickle cell disease is typically marked by infections and that particularly occurs with the loss of spleen function. So, that changes as we go into adulthood or adolescence. And of course, in childhood, the acute pain episodes can occur and in childhood, there's a stroke risk as well.

So, adolescence, it's marked by an increase in the frequency of pain episodes and school disruption can occur, and the patients are transitioning from parent-managed care to self-managed care. So usually, there can be some delay in that area.

Also, from a pediatric standpoint, there's more of a combined care or more multiple specialties are often involved in the patient's care with pediatrics. So, it's usually a little bit more involved. But as they transition to adulthood, the pain can be more chronic and it can be more cumulative organ damage as patients age. And it typically affects the kidneys, lungs, eyes, and bones as we age with sickle cell disease and often frequent hospitalizations.

So, you asked the question since pain is the hallmark of sickle cell disease, what should patients tell providers when they present to the ER? So, the main thing is if a patient has a pain plan in place, usually, they know what treats their pain, what works best for their pain. So, a pain plan at hand is often the best course when you go into the emergency department.

Melanie Cole, MS: That is great advice. Something really important to note. Now, Dr. Bell, speak a little bit about treatment. What role does lifelong treatment plan play in preventing some of these complications?

Dr. Gary Bell: Well, as China said, the management of the acute pain is separate from the medications that we use to sort of modify the disease process itself. And right now, in the United States, there are three FDA-approved medications for the treatment of sickle cell disease. And the first one that came out was hydroxyurea back in—I think, it was FDA approved in 1998.

And hydroxyurea is considered the gold standard in terms of treatment, because it has shown its usefulness over the years. And it's an oral medication, you take it by mouth. And it's usually started at a very young age, and the goal is to address the underlying issues in sickle cell disease that can cause chronic problems if the disease itself is not addressed at an early age. And hydroxyurea actually helps the body make more of the fetal hemoglobin. That is the hemoglobin that may be present when a child is born. And it keeps the red blood cells that are circulating healthier, and it helps prevent them from sticking to the walls of the blood vessels. And thus, as China said, causing clogging of the blood vessels, which delays the delivery of oxygen to the organs and tissues, and thus precipitating the painful crisis.

And hydroxyurea also helps cut down the level of inflammation in the body as well, because we've learned over time that sickle cell disease is a chronic inflammatory process. So if you address inflammation, you can address sickling and pain crises. And hydroxyurea as well helps keep the lining of the blood vessel itself healthier and thus also decreasing the incidence of blocking those blood vessels and causing the crisis.

Another drug that's used is called Adakveo, and Adakveo is a medication that is administered by IV infusion. That is the patient will come into our clinic and get a monthly infusion of that medication. And what Adakveo does over time is that it reduces the painful crisis in terms of its severity and frequency. And say, if that person goes into the hospital, Adakveo has been shown to decrease the length of stay that that person has to stay in the hospital because it decreases the length of the crisis. It's given in the clinic and it's tolerated well by patients. Adakveo works by decreasing that stickiness that we talked about, that the blood cells experience prior to and after sickling.

The third medication is Endari, and Endari actually is a powder. It's taken orally, taken twice a day and it too reduces the pain crises and reduces the incidence of something called acute chest syndrome, which mimics an infection. But it can be very severe in terms of debilitating and increasing the length of stay in the hospital. So, Endari addresses that. Endari also decreases the frequency of hospitalizations and the number of days stayed in the hospital as well.

Melanie Cole, MS: Dr. Bell, can it ever be cured?

Dr. Gary Bell: Well, the cure addresses a treatment, I think, that aims at permanently correcting or bypassing the underlying genetic defect in sickle cell disease rather than managing the symptoms, the painful crises, the hospitalizations, and such. And right now, there are two cures for sickle cell disease, and one is bone marrow or stem cell transplant.

And bone marrow transplants is reserved for patients with more severe sickle cell disease but is also reserved for patients who are relatively healthy and don't have any of the long-term organ complications that can come from chronic sickle cell disease like kidney failure, chronic kidney disease, or pulmonary hypertension, which is an elevated blood pressure in your lungs that can cause a dependency on oxygen or congestive heart failure.

So, you don't want to get sickle cell disease and allow it to progress till you have organ damage, which would put you out of contention for a possible bone marrow transplant. And with bone marrow transplant, of course, you need a donor. So, the ideal donor would be a sibling-matched donor. And, I think, less than 15% of the time, you find a sibling-matched donor.

And the other curative therapy is gene therapy, where the patient's own stem cells are used to make new blood that's higher in fetal hemoglobin or anti-sticking hemoglobin. It's a very extensive process, gene therapy is, and it's also very expensive. So, you have those limitations when it comes to curative therapy when you talk about bone marrow and gene therapy.

Melanie Cole, MS: That's so interesting. It's a very exciting time, Dr. Bell. That was great information. Thank you. Now, China, many people with sickle cell disease experience gaps in care when they transition from pediatric to adult medicine. Tell us a little bit about why you feel this happens and why it's so important to establish that ongoing care, that continuum of care with an adult sickle cell specialist.

LaChina Hollis: So, yes, that's actually a great question, and there are a lot of studies that are out now that show that the transition from pediatric to adult care is a really high-risk period. And sickle cell disease is a disease that has to be managed lifelong. So, it means you have to have a continuity of care.

So, a lot of patients become lost during this transition period because they come from a really highly coordinated pediatric system. Parents are involved, the appointments are scheduled, school accommodations are arranged in the pediatric setting. Oftentimes, you know, pediatric hematologists, they know the patient from top to bottom. They know the patient's history really well. And so, around adolescence, you lose some patients because the patients are growing up and they're less interested in healthcare at that point.

And so, when the patients are transitioning to young adulthood, oftentimes they don't want as much care, they don't want as much involvement. So, we have to really have some good programming in place to keep up with their care and to force continuity. So often, there are other reasons for gaps that include the transfer from familiar pediatric teams to unfamiliar adult teams. And also, there's some difficulty in finding hematologists that have specific skill sets in sickle cell disease or expertise in sickle cell disease.

And another big issue, that loss of parental involvement is huge because the patients become responsible for their own care. They become responsible for any changes in insurance, or they have losses in pediatric coverage. Sometimes transportation can be an issue or employment, or when they transition to college, finding programs that support sickle cell disease is hard.

So, mental health, social challenges, those can also be some things that interfere with that transition. So, you did ask about why is it important to establish with a sickle cell specialist. It's really important because sickle cell disease is far more than just the management of an occasional pain crisis. It's really a lifelong multi-system disease that has so many complications, and these complications can accumulate even when our patients aren't going through sickle cell crisis. So, adult specialists can provide that continuity and proactively monitor for, you know, things like kidney disease or pulmonary hypertension, retinopathy, avascular necrosis, strokes, which are some of the things that can happen secondary to sickle cell disease.

Melanie Cole, MS: Well, thank you for that. So, Dr. Bell, what can people do to manage the disease, reducing their risk of a crisis? Speak about some common triggers and really when you feel it's important that someone seek emergency care

Dr. Gary Bell: Well, you know, here in the clinic, I think one of the things we stress is managing stress. That is avoiding anything or activity that puts the body under stress. And when the body is under stress, patients start to experience crisis. We begin to see the effect of that blocking of blood flow and oxygen to the organs.

And as China said, the primary manifestation of that is pain. And some of the common triggers that we talk about all the time, temperature changes. You know, whether you're going from a warm environment into a cold environment, that's enough stress to cause blood cells to sickle. And we encourage patients to dress appropriately for conditions.

And sometimes we don't think about this. Like, you can go into a restaurant on a day like today where the temperature is 95 outside, and you go into a restaurant where the temperature is 75, and you don't have a sweater on. By the time you get home, if you're a sickle cell patient, you may go into crisis. So, we encourage patients to appropriately dress, both in the winter and the summer.

One of the things that myself, as someone who doesn't have sickle cell disease, when you get on an airplane, they can freeze you out. And if you're not prepared for that, that can cause you to have a pretty long trip or spoil a vacation or something like that.

Anything that lowers the level of oxygen in your blood, say if you are a young 15, 16-year-old who's playing high school sports, and you get out on the football field and overexert yourself, you may precipitate a crisis. I had a patient who recently went to Mexico and went into the mountains, and that precipitated a crisis because he wasn't prepared for the lower level of oxygen in the mountains, and his body reacted to that, and he went into crisis while he was out of the country.

Another common thing that lowers oxygen levels can precipitate hospital admissions is an infection. So, we try to address infections quickly because it can lead to some devastating consequences. It can prolong hospitalizations. And if the infection is not treated appropriately, death could result.

Another thing that we try to manage and trying to get better at addressing is anxiety and depression and emotional issues that can either be precipitated by the disease itself, because again, this is a chronic disease and not only is it chronic, but it manifests itself with pain. And someone in chronic pain has to deal with depressive symptoms.

Life stressors in this community of patients can cause anxiety and depression. All of that affects the response of the body to that stress. That's why it's important that we in the clinic, we aggressively try to get these patients plugged into behavioral health programs so that we can remove that variable in terms of stress.

Melanie Cole, MS: Well, thank you for that. I'd love to give you each a chance for a final thought here. So, Dr. Bell, I would like you to offer your best advice to patients about working with their physicians on some of those exciting treatments you were discussing, on trying to follow the course of the condition and really work with those multidisciplinary specialists so that they can get the best care.

Dr. Gary Bell: Well, the thing to remember in all of this is that sickle cell disease is a chronic condition. And, you know, I reflect back 35 years ago, my brother succumbed to sickle cell disease. And back then, there was not the treatment modalities that we have today. You had dedicated physicians who addressed mainly pain.

Now, we have different modalities that sickle cell specialists and, in some cases, primary care providers, can provide to these patients. But I think the important thing for our patients is to be educated about their disease. They know themselves better than we do. They know when something very subtle means something very big in terms of their health.

So, getting other providers involved, whether it's the hematologist, whether it's physical therapist, whether it's behavioral therapist, it's a collaborative effort that in the end, when we're all working together as a team, we can have much better outcomes for our patients.

Melanie Cole, MS: China, last word to you. I'd like you to speak now to the family members, the friends and caregivers that love these patients. How do they support someone living with sickle cell disease throughout their life? What would you like them to know about the help that's out there at Prisma Health for the entire family and the whole person?

LaChina Hollis: It is really important for families to establish care with centers that are similar to the Lifespan Center that we have here at Prisma Health. So, it is exactly what it means. The Lifespan Center, we want to help patients as they age with sickle cell disease by forming that support system that they need.

So, we're not there just for the patients, we're there for their families too, and providing education and having clinical staff to assist with community needs as well, connecting patients with community-based organizations just feeding into that support system that they need.

Another thing is focusing on what the patient is actually going through. Believe the patient's pain. We often hear that with our patients that they don't feel as if they're heard or listened to. So, actually listening to our patients and meeting their needs, meeting our patients where they are, and helping them to manage sickle cell crisis, helping them to prevent sickle cell crisis, and helping them with their emergency plans and making our families aware of their emergency plans as well.

So, just becoming an overall support system for our patients that are living with sickle cell disease is one of the most important things for our families, their friends, their caregivers, and their overall support system.

Melanie Cole, MS: Thank you both so much for joining us today and really sharing your incredible expertise for our listeners. And to hear more podcasts from our experts, please visit our website at prismahealth.org/podcast. I'm Melanie Cole. And we'd like to invite our audience to download, subscribe, rate, and review Flourish: A Prisma Health Podcast on Apple Podcasts, Spotify, iHeart, and Pandora. Thank you so much for listening to Flourish: A Prisma Health Podcast.