Donor glucose-6-phosphate dehydrogenase deficiency decreases blood quality for transfusion.

Journal Article (Clinical Trial;Journal Article)

BACKGROUNDGlucose-6-phosphate dehydrogenase (G6PD) deficiency decreases the ability of red blood cells (RBCs) to withstand oxidative stress. Refrigerated storage of RBCs induces oxidative stress. We hypothesized that G6PD-deficient donor RBCs would have inferior storage quality for transfusion as compared with G6PD-normal RBCs.METHODSMale volunteers were screened for G6PD deficiency; 27 control and 10 G6PD-deficient volunteers each donated 1 RBC unit. After 42 days of refrigerated storage, autologous 51-chromium 24-hour posttransfusion RBC recovery (PTR) studies were performed. Metabolomics analyses of these RBC units were also performed.RESULTSThe mean 24-hour PTR for G6PD-deficient subjects was 78.5% ± 8.4% (mean ± SD), which was significantly lower than that for G6PD-normal RBCs (85.3% ± 3.2%; P = 0.0009). None of the G6PD-normal volunteers (0/27) and 3 G6PD-deficient volunteers (3/10) had PTR results below 75%, a key FDA acceptability criterion for stored donor RBCs. As expected, fresh G6PD-deficient RBCs demonstrated defects in the oxidative phase of the pentose phosphate pathway. During refrigerated storage, G6PD-deficient RBCs demonstrated increased glycolysis, impaired glutathione homeostasis, and increased purine oxidation, as compared with G6PD-normal RBCs. In addition, there were significant correlations between PTR and specific metabolites in these pathways.CONCLUSIONBased on current FDA criteria, RBCs from G6PD-deficient donors would not meet the requirements for storage quality. Metabolomics assessment identified markers of PTR and G6PD deficiency (e.g., pyruvate/lactate ratios), along with potential compensatory pathways that could be leveraged to ameliorate the metabolic needs of G6PD-deficient RBCs.TRIAL NCT04081272.FUNDINGThe Harold Amos Medical Faculty Development Program, Robert Wood Johnson Foundation grant 71590, the National Blood Foundation, NIH grant UL1 TR000040, the Webb-Waring Early Career Award 2017 by the Boettcher Foundation, and National Heart, Lung, and Blood Institute grants R01HL14644 and R01HL148151.

Full Text

Duke Authors

Cited Authors

  • Francis, RO; D'Alessandro, A; Eisenberger, A; Soffing, M; Yeh, R; Coronel, E; Sheikh, A; Rapido, F; La Carpia, F; Reisz, JA; Gehrke, S; Nemkov, T; Thomas, T; Schwartz, J; Divgi, C; Kessler, D; Shaz, BH; Ginzburg, Y; Zimring, JC; Spitalnik, SL; Hod, EA

Published Date

  • May 1, 2020

Published In

Volume / Issue

  • 130 / 5

Start / End Page

  • 2270 - 2285

PubMed ID

  • 31961822

Pubmed Central ID

  • PMC7191001

Electronic International Standard Serial Number (EISSN)

  • 1558-8238

Digital Object Identifier (DOI)

  • 10.1172/JCI133530


  • eng

Conference Location

  • United States