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Impact of donor biology on stored RBC metabolism
Red blood cells from female and over 60 donors have lower levels of oxidative hemolysis and increased energy and antioxidant metabolism
Following the observations by Kanias and colleagues in the original REDS-III cohort of donors, in the subpopula- tion of recalled donors (that included the extreme low and high hemolysers from phase I) we noted that RBC from female donors had lower oxidative hemolysis than male counterparts, especially in the age window between 30 and 60 years of age (Figure 4A). This observation held true independently of storage duration (Figure 4B) and at any given storage day tested in this study (Figure 4C). Principal component analysis noted that donor sex explained 6.7% of the total metabolic heterogeneity
across donors (Figure 4D), in the absence of any measur- able confounders related to storage duration, storage additive or donor age/ethnicity between the two groups (Figure 4E). GSH levels were significantly higher in RBC from female donors at any given time point tested in the study (Figure 4F-G). This observation was in part explained by increased levels of early glycolytic metabo- lites in RBC from female donors (independently of stor- age day), suggestive of a potential switch from glycolysis towards the PPP to generate reducing equivalents – as supported by higher levels of PPP intermediates and end- products in this group (Figure 4H). This metabolic rewiring was accompanied by higher ATP but lower DPG levels, and overall lower methionine and S-adenosylho-
AB
DE
C
Figure 6. Glucose 6-phosphate dehydrogenase (G6PD) deficiency (A) is a critical factor influencing oxidative hemolsysis. Genome wide association study analysis (GWAS) (B) in a subset of the recalled donor population in the REDS-III study (C). Biomarker analysis of metabolomics data identifies pyruvate and pyruvate/lactate ratios (D), dopamine and glyceraldehyde 3-phosphate (E) as a potential predictor of G6PD deficiency. G6PD: glucose 6-phosphate dehydrogenase; GSH: reduced glu- tathione; GSSG: oxidized glutathione; NADPH: nicotinamide adenine dinucleotide phosphate, reduced; WT: non-G6PD deficient. AUC: area under the curve.
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