Clinical Presentations Associated With Sickle Cell Disease

Peter Salgo, MD: One of the reasons that you get anemia with this disease, when you get anemia, is the red cells destroy themselves. But then we have these other clinical presentations. I have a practice in a hospital in the upper part of Manhattan. You see all of these presentations, not just anemia. So what, there’s vaso-occlusive crisis [VOC], right? What on earth is that? Tell me about vaso-occlusive and other issues that all of this produces.

Sophie Lanzkron, MD, MHS: The most common complication that we’ve seen in folks with sickle cell disease is the vaso-occlusive crisis. These are these painful episodes where you have blockage of the microcirculation, and areas distal to the blockage become hypoxic and you end up with pain. And that’s the most common manifestation, these acute episodes of pain.

Peter Salgo, MD: And there’s pulmonary hypertension, right?

Sophie Lanzkron, MD, MHS: The next one I might move to from the acute stage is acute chest syndrome, which is the one we associate with a lot of mortality and other acute lung disease. Patients can get pulmonary hypertension.

Peter Salgo, MD: You’re talking to an intensivist here.

Sophie Lanzkron, MD, MHS: There are probably about 6% of patients with sickle cell disease who will have pulmonary arterial hypertension. There are other forms of pulmonary hypertension patients can get. We do things like echocardiograms where we can identify echo-defined pulmonary hypertension, which we know is associated with morbidity and mortality.

Peter Salgo, MD: Why do people with sickle disease, and I’ll lump all of this together as sickle disease if that’s OK with you guys, why do they have infectious disease issues? Why do they have problems?

Jane Hankins, MD, MS: Can I say a little bit about the spleen?

Peter Salgo, MD: Sure.

Jane Hankins, MD, MS: Since that is linked to the spleen. One of the acute complications in children with sickle cell disease is when the spleen is affected. So, 2 things can happen in the spleen. One, the spleen can die, and in fact, 90% of the kids with SS disease, they lose their spleen by 2 years of age. Then you are really predisposed to infections from all of the encapsulated organisms. The main one is pneumococcus, they call it strep pneumo [streptococcus pneumoniae]. And then you can have pneumonia, you can have meningitis, then you can die of sepsis. And the other thing, your spleen can grow. You can have splenic sequestration, and that is a severe complication and can kill the child. So, since I’m a pediatric hematologist, that’s 1 of the 2 things that I do the most in those first years of life because infection can kill the child and splenic sequestration can kill a child.

Peter Salgo, MD: If you start blocking the microcirculation, it occurs to me that end organs are all at risk, whether it’s a kidney, microvascular, the bones, avascular necrosis. Is this all of a pattern? Is it all from microvascular occlusion, or is there some other process going on?

Sophie Lanzkron, MD, MHS: There are so many downstream effects of having this abnormal hemoglobin. There’s lots of endothelial dysfunction. You end up with strokes. There’s a multitude of chronic inflammation. It’s considered a hypercoagulable state, so there are a multitude of complications associated with the abnormal hemoglobin.

Jane Hankins, MD, MS: That’s what we see. I think it’s a combination of several factors. Their vessels are sick, their cells are sick, they’re adhering to the endothelium, there’s inflammation, there’s hypercoagulation.

Biree Andemariam, MD: And we’re beginning to know that other cells are involved, too, and I think that’s going to be important when we talk about novel therapies.

I think we’ve all grown up thinking, and some of us have grown up for longer, but I think we’ve all grown up thinking that it’s all about the red blood cell. And I think it’s important that we educate everybody about the newer knowledge that the white cells, and platelets, and endothelial cells are sick and play an important role.

Peter Salgo, MD: This is a systemic disease.

Elliot Vichinsky, MD: I think it’s important to separate pain and sickle cell disease because their progressive disease may not be linked to their pain alone. While pain is a severe complication, it is 1 of the symptoms, but there are many patients who never have a pain crisis, or a serious one. And when they become adults, they can develop severe renal failure, they can lose their hips, they can have a massive stroke, and their whole childhood was characterized as few episodes of pain. The phenotypic expression of the disease actually separates into different categories. And patients who have relatively high hemoglobin tend to have more pain, and those with very low hemoglobin have very few pains, but they have very progressive risk factors for early death. So, pain is what the emergency department doctors see, but when you look at the patients over time, the organ failure and death are really happening insidiously asymptomatically to the patient.

Sophie Lanzkron, MD, MHS: You get lulled into this false sense that you’re doing well, and patients often think they’re doing well when in fact their organs are quite affected.

Peter Salgo, MD: Because they’re not having these crises.

Sophie Lanzkron, MD, MHS: Exactly.

Peter Salgo, MD: If you look at a patient and you look at their quality of life, let me put them in the same 2 silos, if you’ll permit me to do that. One is the pain silo, which immediately and very loudly tells you we have a problem here. But insidiously the other silo is going silently and destroying end organs, and eventually is the more damaging of the 2. Is that fair?

Jane Hankins, MD, MS: I heard this explanation from a patient that I thought was the best. He said, “This is like having a house and every day you lose a brick from your house.”

Peter Salgo, MD: And that’s it. And you can’t tell until that last brick goes out. It’s like Jenga, right, where everything just falls out.

Jane Hankins, MD, MS: Exactly. Every day 1 piece comes out.

Biree Andemariam, MD: Yes. But I think there’s a third silo when you talk to patients. I hear you, it’s vaso-occlusive pain, it’s chronic organ damage. And we as clinicians worry about both. But I think if you speak to patients, they’re worried about other things that are more practical, like how they feel, their fatigue level, how much sleep they get, chronic pain, their memory, their cognitive function. Patients are telling us that it’s not just about VOCs and they’re learning more and more about the importance of chronic organ damage. But if you ask them, they’re in a third silo.

Peter Salgo, MD: I’ll tell you that as a clinician who doesn’t specialize in this, it’s always been my sneaking suspicion that it’s not vaso-occlusive disease alone. There is something else going on in this disease.

Elliot Vichinsky, MD: There are a lot of pathologic effects that are downstream from the mutation and the membranes stimulating thrombosis, inflammation, a lot of biologic changes. I actually think sickle cell would be a totally different, treatable disease if the medical community wasn’t only focused on pain. In the emergency department or some other things, they characterize the patient in terms of how they do with their pain, and they don’t address these other medical problems.

Jane Hankins, MD, MS: I agree.

Elliot Vichinsky, MD: In a lot of ways, if pain wasn’t the problem, I think the enormous brain injury that sickle cell patients have, both focal and non-focal and progressive neurocognitive decline, would be better treated because they would see it as a neurodegenerative disease.

Peter Salgo, MD: Look, let’s take a look at our emergency department colleagues where a lot of these folks get seen, for lack of a better place to go. They’re swamped, and they’re there to take care of an acute issue, which is often pain. And they are not there for, and we covered the waterfront of all these other issues, which is why there’s a gap, it seems to me, in the care of sickle patients.

Transcript edited for clarity.