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Donor glucose-6-phosphate dehydrogenase deficiency decreases blood quality for transfusion
- Source :
- Journal of Clinical Investigation. May, 2020, Vol. 130 Issue 5, p2270, 16 p.
- Publication Year :
- 2020
-
Abstract
- 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% [+ or -] 8.4% (mean [+ or -] SD), which was significantly lower than that for G6PD-normal RBCs (85.3% [+ or -] 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.<br />Introduction Red blood cell (RBC) transfusion is one of the most common therapeutic interventions for hospitalized patients (1). In particular, chronic transfusions are essential for patients with sickle cell disease [...]
- Subjects :
- United States. Food and Drug Administration
Phosphates -- Comparative analysis
Glucose -- Comparative analysis
Metabolites -- Comparative analysis
Glucose metabolism -- Comparative analysis
Oxidative stress
Oxidation-reduction reactions
Alkaloids
Homeostasis
Monosaccharides
Health care industry
Subjects
Details
- Language :
- English
- ISSN :
- 00219738
- Volume :
- 130
- Issue :
- 5
- Database :
- Gale General OneFile
- Journal :
- Journal of Clinical Investigation
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.624327933
- Full Text :
- https://doi.org/10.1172/JCI133530