General Updates | What is HbSC disease, and how does it differ from HbSS disease in pathophysiology and presentation?

So hemoglobin SC disease is the second most common form of sickle cell disease. In the Netherlands, around 30% of our patient population has hemoglobin SC disease. It is considered more mild, but patients do get the same complications as sickle cell anemia patients, but sometimes at an older age. And I don’t think it’s a benign condition – it’s quite severe, and it can also have, patients with hemoglobin SC disease can have quite severe complications, just like patients with sickle cell anemia. 

So because of the compound heterozygosity for hemoglobin S with hemoglobin C, you have a different disease pathophysiology. So these red blood cells are more dense, more dehydrated, because other ion channel function, especially the potassium chloride co-transporter, is affected in hemoglobin SC disease, resulting in a more dehydrated, denser blood cell. And these cells, they hemolyze less, so there’s less anemia, but the viscosity of the blood is higher. And I think that’s also causing higher incidence of retinopathy. So problems with the eye in sickle cell disease patients or hemoglobin SC disease patients. They do also present with vaso-occlusive events, pain crisis, but also acute chest syndrome. And they tend to have also avascular necrosis and nephropathy. But the retinopathy is the most common feature of hemoglobin SC disease next to the pain crisis, which is the main cause of hospital admission in hemoglobin SC disease. But the patients that have these complications are less than the sickle cell anemia patients. So generally speaking, it might be a milder course. Some patients do not have any problems, but then again, there are also sickle cell anemia patients who do not have that many problems. But for hemoglobin SC disease, I think this is more common that they have less complications. And I think also important, the complications can occur at a later age. 

And the management of the disease so because they have less hemolysis they also have a higher hemoglobin so they have less anemia and therefore there is a problem because they cannot be enrolled in clinical trials because most of the time you have to have some kind of anemia for that. So also there’s no specific therapy for hemoglobin SC disease. There is, of course, hydroxyurea. And the first study that actually investigated, a randomized controlled trial in Africa, showed promising results. But there’s some reluctance sometimes to prescribe this to hemoglobin SC disease patients because they already have a high hemoglobin and you don’t want it to rise. So another treatment that might be interesting is phlebotomy, so bloodletting, where you actually reduce the viscosity and induce an iron deficiency, and we have shown in a few cases that that is beneficial. The sickling tendency is decreased. There also have been retrospective studies that showed beneficial effects of phlebotomy. So what we now try to do is when a patient is more anemic, then hydroxyurea could be an option. And if they have a high hemoglobin, then phlebotomy might be an option. And this is, of course, when patients have complications. Because in our really asymptomatic patients, we only monitor the organ damage, if there’s any organ damage, and we do not start a treatment for this patient group.

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