[HTML][HTML] Donor glucose-6-phosphate dehydrogenase deficiency decreases blood quality for transfusion
RO Francis, A D'Alessandro… - The Journal of …, 2020 - Am Soc Clin Investig
RO Francis, A D'Alessandro, A Eisenberger, M Soffing, R Yeh, E Coronel, A Sheikh…
The Journal of Clinical Investigation, 2020•Am Soc Clin InvestigBACKGROUND 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 …
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 …
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.
The Journal of Clinical Investigation