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

Department of Pathology and Cell Biology, Columbia University Vagelos College of Physicians and Surgeons and NewYork-Presbyterian Hospital, New York, New York, USA. University of Colorado Denver-Anschutz Medical Campus, Aurora, Colorado, USA. Department of Medicine and. Department of Nuclear Medicine, Columbia University Vagelos College of Physicians and Surgeons and NewYork-Presbyterian Hospital, New York, New York, USA. Division of Nuclear Medicine and Molecular Imaging, Icahn School of Medicine at Mount Sinai Hospital, New York, New York, USA. Department of Anesthesia and Critical Care Medicine, Montpellier University Hospital Gui de Chauliac, Montpellier, France. New York Blood Center, New York, New York, USA. Division of Hematology Oncology, Icahn School of Medicine at Mount Sinai Hospital, New York, New York, USA. Carter Immunology Center, University of Virginia School of Medicine, Charlottesville, Virginia, USA.

The Journal of clinical investigation. 2020;(5):2270-2285
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Abstract

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 REGISTRATIONClinicalTrials.gov 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.

Methodological quality

Publication Type : Clinical Trial

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