Donor glucose-6-phosphate dehydrogenase deficiency decreases blood quality for transfusion
| Autor: | Chaitanya R. Divgi, Tiffany Thomas, Debra Kessler, Travis Nemkov, Andrew Eisenberger, Angelo D'Alessandro, Yelena Ginzburg, Joseph E. Schwartz, Beth H. Shaz, Mark Soffing, Francesca Rapido, Julie A. Reisz, Steven L. Spitalnik, Eldad A. Hod, Sarah Gehrke, Arif Sheikh, Francesca La Carpia, Richard O. Francis, James C. Zimring, Esther Coronel, Randy Yeh |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
Male 0301 basic medicine Purine congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty Erythrocytes Blood Donors Oxidative phosphorylation Pentose phosphate pathway medicine.disease_cause Andrology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine hemic and lymphatic diseases Internal medicine parasitic diseases Humans Medicine Hematology business.industry nutritional and metabolic diseases General Medicine Glutathione medicine.disease Glucosephosphate Dehydrogenase Deficiency 030104 developmental biology chemistry Blood Preservation 030220 oncology & carcinogenesis Female Clinical Medicine Erythrocyte Transfusion business Homeostasis Oxidative stress Glucose-6-phosphate dehydrogenase deficiency |
| Zdroj: | J Clin Invest |
| ISSN: | 1558-8238 0021-9738 |
| Popis: | BACKGROUND: Glucose-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. METHODS: Male 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. RESULTS: The 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. CONCLUSION: Based 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 REGISTRATION: ClinicalTrials.gov NCT04081272. FUNDING: The 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. |
| Databáze: | OpenAIRE |
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