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Impact of donor biology on stored RBC metabolism
Operating Characteristic (ROC) curves of metabolic pre- dictors of low and high oxidative hemolysis across the recalled donor population (Figure 3). ROC curves, sensi- tivities specificities and absolute quantitative thresholds for each metabolite are presented in Figure 3. Of note, concentrations of lactate above 13.5 mM, 5-oxoproline (above 68.3 uM), glutamine (8.6 uM), GSH (1.0 mM) and citrulline (1.1 uM) had areas under the curve (AUC) ≥0.7.
Oxidative hemolysis is subject to biological variability across donors
As noted above, end of storage RBC from some donors had similar metabolic phenotypes and oxidative hemolysis to day 10 RBC from other donors and vice versa. In this view, we hypothesized that factors other than storage dura- tion alone may impact RBC oxidative hemolysis and the associated metabolic phenotypes. Consistently, we noted
ABC
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Figure 4. Oxidative hemolysis as a function of donor sex (male vs. female = blue vs. pink) and age (A). Oxidative hemolysis was higher in male donors at any given storage day (B) or storage day 10, 23 and 42 (C). Vice versa, reduced glutathione (GSH) was lower in male donors at any given storage day (F) and in the longitudinal analysis at day 10, 23 and 42 (G). Partial least squares discriminant analysis (PLS-DA) discriminated between male and female donors (D), in the absence of signif- icant enrichment for AS-3 or AS-1 sample in either group (E). Red blood cells (RBC) from male donors have altered glycolysis, lower activation of the pentose phos- phate pathway, altered methionine and citrulline metabolism (samples are plotted with no distinction of storage days, only samples stored in AS-3 are shown in this panel - H). ALL: allantoin; ATP: adenosine triphosphate; CITR: citrate; DPG: 2,3-diphosphoglycerate; E4P: erythrose phosphate; FBP: fructose bisphosphate; GA3P: glyceraldehyde 3-phosphate; GLUC: glucose; GSH: reduced glutathione; LAC: lactate; METH: methionine; PEP: phosphoenolpyruvate; PGLY: phosphoglycerate; PYR: pyruvate; RibP: ribose phosphate (isomers); SAH: S-adenosylhomocysteine.
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