Understanding red blood cell (RBC) subpopulations is crucial for comprehending donor variability and enhancing transfusion outcomes. This review highlights the significance of RBC subpopulations, focusing on the properties of biologically young and old RBCs and underscores how donor variability impacts transfusion outcomes. The role of senescent RBCs in adverse transfusion reactions and the emerging significance of circulating erythroid cells (CECs) is discussed. RBC aging and the role of oxidative stress and aging mechanisms is highlighted. Changes in RBC flexibility, calcium homeostasis, band 3 protein modifications, membrane microvesiculation, 2,3-diphosphoglycerate (2,3-DPG) levels, and immunological markers like CD47 and CD55 contribute to RBC clearance and erythrophagocytosis. Also, methods of characterizing / separating of biologically young and old RBC subpopulations is introduced. This review emphasizes the importance of RBC subpopulations in understanding donor variability and improving transfusion outcomes.
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