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Mean levels of 2,3-diphosphoglycerate (DPG) were significantly increased in erythrocytes (RBC) from 43 nonanemic black blood donors (4.80 ± 0.06 μmoles/1 RBC) compared with 22 white donors 4.47 ± 0.08 μmoles/1 RBC) (p < 0.01). Additional studies were done on RBCs from eight of the 12 black donors with DPG levels > 5 μmoles/1 RBC. Although a potentially hemolytic disorder could be defined in four (AS hemoglobin, β-Thalassemia minor, C6PD deficiency), reticulocyte counts were normal. However, when RBCs from the subgroup were compared to RBCs from an additional 25 unselected white donors, the following suggested an abnormally large population of young RBCs in the subgroup: 1) normal or elevated RBC-ATP with normal serum phosphate level; 2) significantly increased activities of RBC age-dependent enzymes hexokinase (p < 0.02), pyruvate kinase (p < 0.05), and glutamic-oxaloacetic transaminase (p < 0.01), with normal activity of phosphoglycerate kinase, an age-independent enzyme; 3) decreased dense (older) RBCs as determined by sedimentation in phthalate esters. Since DPG is increased in young RBCs and falls as the RBC ages, loss of older relatively DPG depleted RBCs due to shortened survival could account for the elevated DPG levels seen in the subgroup.