It’s in your blood: The impact of age, sex, genetic factors and exposures on stored red blood cell metabolism

Transfusion of packed red blood cell (RBCs) saves millions of lives yearly worldwide, making packed RBCs the most commonly administered drug in hospitals after vaccines. However, not all blood units are created equal. By examining blood products as they age in blood banks, transfusion scientists are gaining insights into the intricacies of human chemical individuality as regulated by biological factors (such as sex, age, and body mass index), genetic and non-genetic factors like environmental, dietary, and other exposures. Here, we review recent literature on this topic, with an emphasis on studies linking genetic traits to the metabolic heterogeneity of blood products, the hemolytic propensity of stored RBCs, and transfusion outcomes in both healthy autologous and non-autologous patients requiring transfusion. Given the role of RBCs as a simplified model of eukaryotic cells, and RBC storage as a medically relevant application modeling erythrocyte responses to oxidant stress, these insights have the potential not only to guide the development of precision transfusion strategies, but also to identify novel mechanisms of RBC metabolic regulation relevant to responses to hypoxia and oxidant stress in human (patho)physiology.