Expert Perspectives on the Optimal Management of Sickle Cell Disease - Episode 3
Key opinion leaders give insight on the presentation of sickle cell disease, also highlighting acute vs chronic complications of the disease.
Ifeyinwa Osunkwo, MD, MPH: Wally, can you talk a little about the acute sickle cell complications and how these differ from the chronic complications? It’s important to highlight that no matter what type of sickle cell disease you have, you are at risk of both acute and chronic complications.
Wally Smith, MD: That’s right. You know, the acute complication that doctors and hospitals know the best is called a vaso-occlusive crisis, or crisis for short. We’ve messed around with terminology to try to better describe it, and I keep coming back to crisis. It is a crisis in the life of the patient because they’re in pain, they want treatment early, and they want treatment immediately. If you intervene sooner, you likely can prevent some of the downstream complications. It’s seen in the emergency departments of many hospitals and in hospital wards around the country. But as you said, the size of vaso-occlusive crises are painful and may cause all kinds of disability and acute organ dysfunction on top of that.
Besides that, there’s this chronic low-level hum of sickling going on all the time in all the blood vessels, in all the organs of every patient with sickle cell disease. Some more than others. And it’s that low-level hum that ongoing crises like complication that you can’t even feel, because it’s the same vaso-occlusive phenomena. That destroys your organs. That causes eventually either liver, lung, eye, brain, heart, kidney, or other failure. Failure of your joints. You get basically rotten hips, rotten shoulders, rotten knees, all due to lack of oxygen getting to those organs and organ death over time. The spleen in most children is gone by the time they’re adults because they’ve been either ischemic or they’ve been trying to filter out those abnormal red cells that I discussed earlier. The spleen is like a trash can, and it’s overworked. By the time they get to be adults, it’s a nub; it’s gone.
Ifeyinwa Osunkwo, MD, MPH: I like how you describe that.
Wally Smith, MD: Patients cannot handle this low-level hum, and their organs 1 by 1 begin to fail. Sometimes they don’t even know their organs are failing.
Ifeyinwa Osunkwo, MD, MPH: That’s a question that I wanted to pose to Abdullah and to Pat. Sometimes patients say, “I’m not having a pain crisis, so I don’t need to see the hematologist. I don’t need to go to the doctor.” I think you see that with pediatric, young adults, teenagers. When they’re not having pain, they’re like, “See you later.” How do you convince them that what Wally says is true? They have this long-standing chronic stuff happening all the time.
Abdullah Kutlar, MD: It’s an excellent point, especially in adolescents and young adults who feel well and who—by luck, by high fetal hemoglobin, or whatever you say—don’t have a lot of acute pain episodes. It’s very difficult. I used to try to persuade patients to be on a disease-modifying therapy, mainly hydroxyurea. Wally, there are some very nice points that we came up with at the end of the MSH [Multicenter Study of Hydroxyurea] follow-up. That shows very nicely that people who have been taking hydroxyurea for most of the time have much lower incidents of death, and that is an eye-opener for many of them. Then you go over different chronic complications. You may not feel pain, but as Wally pointed out, the organ damage is ongoing at that time. It’s still progressing.
Ifeyinwa Osunkwo, MD, MPH: And we still have young adults who have strokes who have never had a pain crisis?
Patrick McGann, MD, MS: Yes, and the paradigm of the disease is really changing as we have these new therapies, which we’ll get into. Wally said that by adulthood your spleen is broken, basically by the time you’re 2 years old your spleen has been shown to be significantly damaged. When I talk to newly diagnosed babies, I talk to them with a much greater sense of optimism than families a decade ago. We start hydroxyurea early and try to protect their organs. It’s a long haul. It’s like a vitamin to keep them healthy. They might hear about pain, but it’s more than pain. For older patients, I try to think of what they might want to do when they get older, whether it’s playing sports or the job that they want to do. If they want to do those effectively, then protecting their organs is an important thing. We try to bring those things up.
Ifeyinwa Osunkwo, MD, MPH: Excellent. This highlights the next comment I’m trying to make here. When you look over years of sickle cell disease, the life expectancy has improved, as you guys mentioned. However, we still have a 3-decade gap between a sickle cell individual and the regular African American who lives in the United States. The median age of sickle cell disease in Africa is 17 years old. That’s dismal. To think the adults in Africa with sickle cell disease are 17 years old, that’s almost embarrassing. In America, they’re still between the 40s and the 50s. You may have some people who live to be 60, 70, and 80, but they’re fewer and far between compared with what we want to see and compared with the general population.
Dr Kenneth Ataga and some colleagues did a minute analysis several years ago. They looked at 41 studies to see the impact of a lower or a dropping of hemoglobin on long-term outcomes of sickle cell disease. It was a very interesting study. This is a little more complex than we can get into in this broadcast, but they showed that a drop in hemoglobin of 0.4 g/dL is enough to increase your risk of having a stroke. A drop in hemoglobin of 0.6 g/dL has an increased risk of kidney problems, pulmonary hypertension, and even the risk of death. And the drop in hemoglobin of 0.9 g/dL increases pulmonary hypertension. It’s really important to remember that it’s not just pain. The hemodynamic changes that are associated with having sickle cell disease cause long-term chronic damage to your organs, as Wally Abdullah, and Pat had mentioned, so we cautiously pay attention. We have a more futuristic way of looking at the patients: How do we protect organs as well as damage control and treat pain as a primary focus of sickle cell disease management?
Transcript Edited for Clarity