Overview of Sickle Cell Disease

Peter Salgo, MD: Hello and thank you for joining this HCPLive® Peer Exchange titled, “Sickle Cell Disease: Diagnosis, Screening, and Treatment.”

Sickle cell disease is an inherited disease that affects red blood cells with an abnormal version of hemoglobin. The disease is associated with acute and chronic complications and shortened life spans. In this HCPLive® Peer Exchange, I’m joined by a panel of my colleagues, all experts in the field of hematology. Together, we will discuss the challenges associated with a diagnosis and the pharmacologic options for the treatment of sickle cell disease.

I’m Dr Peter Salgo. I’m a professor of medicine and anesthesiology at Columbia University College of Physicians and Surgeons. I’m associate director of surgical intensive care at NewYork-Presbyterian Hospital in New York City.

With me today on our distinguished panel are:

Dr Biree Andemariam, associate professor of medicine and director of New England Sickle Institute at UConn [University of Connecticut] Health, in Farmington, Connecticut;

Dr Jane Hankins, associate member in the Department of Hematology at St. Jude Children’s Research Hospital in Memphis, Tennessee;

Dr Sophie Lanzkron, director of the Sickle Cell Center for Adults, and associate professor of medicine at The Johns Hopkins Hospital in Baltimore, Maryland;

And Dr Elliot Vichinsky, chief of hematology/oncology, professor of pediatrics in the School of Medicine at the University of California, San Francisco, in San Francisco, California.

Thank you all so much for being here. I’m glad to meet some of you. Some of you I’ve met before. This is great. Why don’t we start with the real basics here? Somebody want to define sickle cell disease for me? Who wants to start?

Biree Andemariam, MD: I’ll start.

Peter Salgo, MD: Brave of you, go right in.

Biree Andemariam, MD: I think it’s important for people to recognize that sickle cell disease really is the most common hereditary blood disorder worldwide.

Peter Salgo, MD: The most common?

Biree Andemariam, MD: Yes.

Peter Salgo, MD: OK.

Biree Andemariam, MD: And it affects 300,000 babies per year born across the globe. And it’s estimated that here in the United States there are 100,000 Americans living with sickle cell disease.

Peter Salgo, MD: I want to pause this for a minute because those numbers are large.

Biree Andemariam, MD: They’re very large.

Peter Salgo, MD: I think that there’s a tendency for folks who don’t live in endemic areas in parts of our country to underestimate how big a problem this disease is, don’t you think?

Biree Andemariam, MD: In our country?

Peter Salgo, MD: Yes.

Biree Andemariam, MD: I agree with you. I also think it’s important to realize that although sickle cell disease is most common in individuals of African origin and Latino background in this country, that the face of sickle cell disease has told us that just about everybody can be affected.

Peter Salgo, MD: Really?

Biree Andemariam, MD: Yes, I think all of us will have examples in our practices of individuals who are neither black or brown. It’s also seen in individuals from the Mediterranean, from the Saudi Arabian Peninsula, and also in Southeast Asia. It’s not just a black and brown disease, although in this country that’s predominantly what we see.

Peter Salgo, MD: I could broaden this a little bit. Tell me if you agree, all of you. Whether or not you are the person who has this disease, we’re all affected by it. That’s a lot of folks in this country, don’t you think?

Elliot Vichinsky, MD: Yes. The second most common place in the world where sickle cell is, is in India….

Peter Salgo, MD: I want to take your point to an even broader interpretation. You don’t have to have sickle cell, or you don’t have to have an immediate relative with sickle cell to be affected. As a nation, with that many folks with this problem, I think we’re all affected. Is that a fair statement?

Elliot Vichinsky, MD: Well, I would like the country to feel that way. We clearly are, but sickle cell disease has been a disease that has suffered from discrimination because of the ethnicities that it involves. But it clearly affects the country, and there are many people who are carriers or who have other types of sickle cell disease in this country who are not in 1 particular ethnic group.

Peter Salgo, MD: Let’s get some more basic facts on the table, alright? Genetic underpinning of this disease, the difference between the trait and sickle cell anemia.

Jane Hankins, MD, MS: Sure, yes. I was going to add that sickle cell disease is considered a rare disease, but it’s not really because when you look at the distribution of sickle cell disease, it’s concentrated in certain urban areas. The sickle cell disease is caused by a genetic mutation. It’s a single point mutation in the gene that makes the beta-globin, and the beta-globin is what produces part of our hemoglobin, which is the protein that carries oxygen. So when you mess up that beta hemoglobin, when it binds with the other globin, which is the alpha-globin, it creates this hemoglobin that really isn’t behaving very well. And then it likes to bind with other abnormal hemoglobin that we call sickle hemoglobin, and that clogs the circulation or causes vaso occlusion.

Peter Salgo, MD: Let’s go one step further. That’s the genetics. How does this work? In other words, what is the genetic and epigenetic factors that lead to the actual sickling?

Elliot Vichinsky, MD: Before we get there, I’d like to add 1 thing.... Many clinicians feel that anemia is part of the definition of sickle cell disease, and it’s not true. Many of the types of sickle cell disease are not anemic, and they have different physical characteristics. So they often go undiagnosed. The disease itself is really about the pathology of the cells adhering and the problems they have, not anemia. I think that’s important.

Peter Salgo, MD: But we’re going to get there pretty soon, actually right after this. How do these cells, I guess what makes them sickle? We have these hemoglobins, they’re abnormal. What actually goes on? Do we know why they sickle like that? Do you know?

Elliot Vichinsky, MD: Well, yes. I think sickle cell disease is probably one of the best studied molecular diseases historically. There’s been a lot of work into understanding that. And basically, hemoglobin is made up of 2 alpha and 2 beta chains, and when you’re in utero, you make mainly alpha chains and gamma chains. And after birth or around then, you start making the adult hemoglobin A. These people have a mutation that converts that to the sickle hemoglobin.

And they don’t have symptoms in utero, but with this point mutation, it results in the hemoglobin being OK, relatively OK when the cell is oxygenated, but when the oxygen drops, the polymers or the molecules inside the cell, where they’re kind of floating around, suddenly become rigid and they stick together and they deform the cell. And they make the cell have that sickle shape, but in addition, the membrane dramatically changes, and the inside of the membrane flips to the outside and exposes a great number of phospholipids and changes that induce a remarkable explosion of inflammatory and thrombotic products. And it destroys the membrane, so the cell basically starts falling apart very early.

Sophie Lanzkron, MD, MHS: I wanted to go back to the genetics for a moment and just remind people that there are several different types of sickle cell disease. People can be homozygous for the hemoglobin S mutation and have SS disease, but then there’s SC disease and S beta-plus thalassemia, and as we talk about therapies, it’s going to matter what kind of genotype patients have.

Peter Salgo, MD: That’s why they pay you the big bucks. You know these things.

Transcript edited for clarity.