Sex discrepancies in blood donation: Implications for red blood cell characteristics and transfusion efficacy

Red blood cell (RBC) transfusions carry risks, and the mechanisms mediating adverse transfusion outcomes are not fully understood. This review explores the impact of donor sex and donor-recipient sex mismatch on RBC characteristics and transfusion outcomes. Females, at least those in their reproductive age, have a higher proportion of young RBCs in the circulation when compared to males, associated with higher post transfusion recovery. Also, female RBCs exhibit a greater resilience to the storage lesion, with lower hemolysis rates and better rheologic properties. Despite these qualities, transfusion of female RBCs may be associated with adverse transfusion outcomes, such as pulmonary injury, increased mortality, and immunomodulatory effects, which may differ depending on the sex of the recipient, although not all observations are consistent. As a potential mechanism, the presence of immature RBCs, especially reticulocytes, in transfused blood is associated with immunomodulatory effects. Reticulocytes contain residual cellular components which can interact with surrounding blood cells and endothelial cells, in particular in neonates and cancer patients. Understanding the influence of donor sex and RBC age-subpopulation on RBC quality, and investigating the risks and benefits of immature RBCs in transfusions, offers opportunities for optimizing transfusion practices.