{"doi":"10.1172/jci133530","title":"Donor glucose-6-phosphate dehydrogenase deficiency decreases blood quality for transfusion","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.","journal":"Journal of Clinical Investigation","year":2020,"id":53337,"datarank":2.0870864133015017,"base_score":4.77912349311153,"endowment":4.77912349311153,"self_citation_contribution":0.7168685239667295,"citation_network_contribution":1.370217889334772,"self_endowment_contribution":0.7168685239667295,"citer_contribution":1.370217889334772,"corpus_percentile":null,"corpus_rank":null,"citation_count":118,"citer_count":47,"citers_with_citation_signal":34,"citers_with_endowment":34,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9232,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT04081272"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":28360,"name":"Angelo D’Alessandro","orcid":"0000-0002-2258-6490","position":1,"is_corresponding":false},{"id":271748,"name":"Andrew Eisenberger","orcid":"0000-0001-6846-5099","position":2,"is_corresponding":false},{"id":273108,"name":"Mark Soffing","orcid":null,"position":3,"is_corresponding":false},{"id":271749,"name":"Randy Yeh","orcid":"0000-0003-2945-5546","position":4,"is_corresponding":false},{"id":273109,"name":"Esther Coronel","orcid":null,"position":5,"is_corresponding":false},{"id":271750,"name":"Arif Sheikh","orcid":"0000-0002-4140-2052","position":6,"is_corresponding":false},{"id":271751,"name":"Francesca Rapido","orcid":"0000-0001-9616-3039","position":7,"is_corresponding":false},{"id":225935,"name":"Francesca La Carpia","orcid":"0000-0002-1120-9307","position":8,"is_corresponding":false},{"id":110268,"name":"Julie A. 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