Shedding light on a neglected form of sickle cell disease

Sickle cell disease (SCD) is a group of painful and life-threatening genetic disorders that affect hemoglobin, the major protein that carries oxygen in red blood cells. It occurs in nearly 100,000 people in the United States and millions worldwide.

The most common type is hemoglobin SS (HbSS), which affects about 65% of those with sickle cell disease. Less familiar and understudied is hemoglobin SC, or HbSC, the second most common type, which affects about 25% of those with sickle cell disease. Clinicians have long regarded HbSC as a “mild” type of the disease, but a new study published in the British Journal of Haematology challenges that notion.

The research is led by Julie Kanter, M.D., a professor at the University of Alabama at Birmingham and director of the school’s Adult Sickle Cell Program. Conducted as part of the Sickle Cell Disease Implementation Consortium (SCDIC), the study included 2,282 individuals ages 15–45 years, with sickle cell disease. About 500 (22%) had HbSC. For the study, the researchers compared clinical outcomes in people with HbSC to those with HbSS over a median period of about five years.

In a recent conversation, Kanter discussed the findings of the new study and what they may mean for people living with HbSC.

Why did you undertake this research on HbSC?

I wanted to try to clear up some of the misconceptions about the disease. For example, in childhood, many people with HbSC have milder manifestations of their sickle cell disease and fewer complications than those with HbSS. However, as they become adults, many with HbSC have complications that are clinically just as severe as they are in people with other types of sickle cell disease. Yet there are fewer studies and medications targeting this group.

What did you find in your study? Anything new or surprising?

We expected to see complications in adults with HbSC that were similar to those in adults with HbSS. But we were surprised to see higher rates of depression in the HbSC cohort. Many in this cohort also had significant retinopathy, an eye disease, as well as avascular necrosis, a disease of the bones.

We think the retinopathy and avascular necrosis in people with HbSC is related to a higher viscosity or thickness of the blood, which seems to cause complications in the blood vessels. We also saw many people with complications involving the spleen, the organ that filters the blood. Unfortunately, these complications are poorly understood. In general, we found that HbSC is more clinically severe than previously thought.

What do you think needs to be done to improve these outcomes?

Overall, sickle cell disease has suffered from over a century of neglect. But within the large group of disorders, HbSC and the people who have it are even more neglected. There are no good animal models of HbSC, and research progress has been even slower than for others with SCD.

We need to increase our understanding of this type of sickle cell disease, develop targeted therapies, and most of all ensure the people living with it remain under care throughout childhood. That way they can see sickle cell disease specialists before they begin developing complications as adults.

Will these findings help in other areas of sickle cell research?

Yes, these findings help advance the understanding of all forms of sickle cell disease, and the large health data networks we’re using are making that possible. For example, the National Alliance of Sickle Cell Centers has adopted the Globin Research Network for Data and Discovery registry to use as a national resource to better understand different genotypes and phenotypes within SCD, including HbSC. This helps improve care for everyone with the disease. The registry is now being used in more than 50 SCD centers.

What’s next in your research on HbSC?

We have several ongoing projects. We are working to better understand and treat one of the more devastating complications of sickle cell disease, multiorgan failure syndrome, that occurs frequently in people with HbSC disease. We want to ensure affected persons are quickly transferred to sickle cell centers.

Is there anything else that could help people in this population?

We need people who work in drug development to not neglect the people living with HbSC disease when designing clinical trials. These individuals are routinely excluded from clinical trials because they add additional variables that can complicate the trial.

As a result, researchers often choose similar types of patients within a group, and because HbSS is more common, patients with that form of SCD are the ones most often chosen. However, people with HbSC need their own cohorts in each clinical trial to ensure they are not left out as the efforts to find new medications and therapies progress.