New research investigates differences in sickle cell disease between the sexes

A new paper from researchers at King's, in collaboration with Muhimbili University in Dar es Salaam, provides an in-depth analysis at why people of the female sex may have milder symptoms for sickle cell disease, specifically looking at differences in hemoglobin.

Sickle cell disease (SCD) refers to a group of diseases where red blood cells are rigid and abnormally shaped. This is due to the cells having an abnormal version of hemoglobin—the protein that allows red blood cells to carry oxygen. As a result of their shape and rigidity, they have a shorter lifespan and are more likely to block blood vessels causing vascular damage and inflammation.

It's well understood that people with SCD have milder symptoms when they have more F-cells—a specific type of red blood cell with fetal hemoglobin. During the fetal stage, it's common for red blood cells to have this version of hemoglobin but this is lost in most of your cells by adulthood. However, some people with SCD display higher than average levels of F cells, which researchers believe is due to their ability to survive longer in the bloodstream than the sickled versions of red blood cells.

The female biological sex has been identified as one factor that generally promotes a higher level of F cell circulation. In this study, researchers at King's including Dr. Stephan Menzel and Dr. Sara El Hoss, from the Red Cell Hematology Lab, looked to compare F cell production and changes in their abundance between female and male SCD patients.

The results, published in the American Journal of Hematology, found that there were significantly higher levels of F-cells in female patients. This created a higher percentage of fetal hemoglobin without a significant difference in the total amount hemoglobin in the bloodstream.

Another interesting observation was made when looking at F-retics—a young version of red blood cells (with fetal hemoglobin) that are not yet fully developed. Results showed a higher percentage of F-Retics (when compared to mature red blood cells) in females. This suggests that a reason for the higher level in F-cells between the sexes is two-fold: more of them are produced in the female bone marrow, and such cells also have a better survival rate circulating in the bloodstream.

New potential therapies being developed for SCD are aiming to stimulate the development of fetal hemoglobin within patients. The researchers hope that understanding the causes behind this difference between the sexes will help the development of these therapies.