Overview of Sickle Cell Disease: Pathophysiology and Clinical Burden


An overview on the pathophysiology of sickle cell disease and expert perspectives on the clinical (and psychosocial) burden it presents.


Ifeyinwa Osunkwo, MD: Hello, everybody. My name is Ifeyinwa Osunkwo; I’m a professor of medicine and pediatrics, and I’m the medical director for the sickle cell disease enterprise at the Levine Cancer Institute at Atrium Health in Charlotte, North Carolina. Today I have some amazing colleagues of mine, and we’re here to have a conversation at HCPLive© Peer Exchange titled “Emerging Treatment Options for the Management of Sickle Cell Disease.” I’m going to get us started by introducing our guests and have them give us a little of their background, starting with Dr Wally Smith.

Wally R. Smith, MD: Hi, I’m Wally Smith. I’m a general internist by training, but I’ve been caring for patients with sickle cell disease at 2 institutions. I’m currently the Florence Neal Cooper Smith professor of sickle cell disease at Virginia Commonwealth University and the director of the adult medical home.

Ifeyinwa Osunkwo, MD: The next panelist is Dr Nirmish Shah.

Nirmish Ramesh Shah, MD: Hi, I’m Dr Nirmish Shah. I’m the director of the sickle cell transition program at Duke University. I take care of both kids and adults, and I love working with kids as they grow up into young adults and become successful.

Ifeyinwa Osunkwo, MD: Last but not least is an amazing friend of mine, Dr Payal Desai. Not that you others are not amazing, but I want to have Payal introduce herself.

Payal Desai, MD: Thank you, Ifey. I’m Payal Desai. I’m transitioning, but I was the head of the adult sickle cell comprehensive center at Ohio State University. I look forward to chatting with all of you.

Ifeyinwa Osunkwo, MD: Let’s start our discussion by talking about an overview of sickle cell disease. I’m going to pose this to Dr Shah. Can you give us a brief overview of sickle cell disease? The different genotypes, and how the genetic inheritance works so that people who are listening can understand what sickle cell disease is and how it’s inherited for people who typically get it in the United States?

Nirmish Ramesh Shah, MD: It’s good to understand the basics. Sickle cell disease is an inherited disease; you get it from mom and dad. It’s not contagious; it’s not something you get from the water. Many times, mom and dad don’t even know they’re carriers for sickle cell disease. [For example], let’s say the mom knows she’s a carrier for the sickle cell trait and the dad may not know, but then they have a child. They come to our clinic, and they have a new diagnosis of sickle cell disease. What we see with sickle cell disease is that there’s a small change in the genetics that causes the blood to change shape. There are a lot of interesting things that cause that to happen, but in the end, when it changes its shape, the blood turns into the sickled shape, and then it can get stuck in the blood.

Of course, if blood doesn’t get to go where it needs to go, that causes problems, and there are different types of sickle cell disease. If you have this 1 classic sickle mutation, this 1 sickle change, there are other things that you inherit with it that also are sickle cell disease. The most common is type SS, but there’s also SC, S beta-plus, and S beta-zero. There are different types of sickle cell disease, but they all have that sickle gene, and that’s what unifies the diagnosis. You’re bringing up a good point: not every patient is the same. We have some SS patients who do really well and some who have some more speed bumps than others, and they have some more complications. We need to keep in mind that even if you have a genotype that’s of more concern than maybe another type, we must watch every patient closely.

Ifeyinwa Osunkwo, MD: Excellent. It’s a disease that affects people differently, so you may have the same mutation, but it may show up differently depending on multiple factors. Dr Desai, can you briefly discuss the prevalence and the disease burden? How does sickle cell affect children vs adults, and what are the unmet needs for sickle cell disease?

Payal Desai, MD: The first thing, as Dr Shah said, is that the genotype does not always express phenotype. This means that what people have doesn’t always define what complications they’re going to have, but the primary thing we think about with sickle cell disease is pain. For some children, that starts as young as 6 to 9 months of age. For some adults, they can have 1 episode their entire life. Those episodes of pain can happen infrequently, or they can happen 4 or 5 times a year. They can be so severe that people have to be in the hospital for support: pain medications, IV [intravenous] fluids, watching for complications.

We focus a lot on pain, and that’s the primary reason people seek medical care or think about sickle cell disease, but there are many other complications to think about. Just as the pain is a manifestation of a vaso-occlusive episode where the blood flow decreases in different parts of the body, it can affect the organs in silent ways. It can affect the heart, the kidneys, the brain—anywhere the blood flows. I frequently describe it to my patients as almost like mini heart attacks. You’re decreasing the flow to anywhere, and we all know what a heart attack is. Where you have less blood flow, it causes damage to that area. Hopefully, the blood eventually flows again, but you may have some permanent damage. It can impact all your health.

The other part that’s really neglected is watching all those organs. And then what does that do to the person’s quality of life in the long term? What happens to their mental health dealing with a chronic illness that they can’t predict so they can’t plan like the rest of us? In the same way, if they have a lot of complications, they can’t plan if they have a homework assignment due. They can’t plan to go to the prom. I’ve had patients come in the day before their wedding—the stress of it, the implications of it. They can’t plan for life events in the same way. Sometimes those disappointments can have impact on their mental health over time.

Ifeyinwa Osunkwo, MD: In conclusion, it’s a disease of lifestyle disruption, quality-of-life disruption, as well as acute exacerbations and progressive organ damage.

Transcript edited for clarity.

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