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Haematologica 2021 Volume 106(5):1290-1302
Blood Transfusion
Donor sex, age and ethnicity impact stored red blood cell antioxidant metabolism through mechanisms in part explained by glucose 6-phosphate dehydrogenase levels and activity
Angelo D’Alessandro,1,2,3 Xiaoyun Fu,4 Tamir Kanias,3,5 Julie A. Reisz,1
Rachel Culp-Hill,1 Yuelong Guo,6 Mark T. Gladwin,5 Grier Page,6
Steve Kleinman,7 Marion Lanteri,8 Mars Stone,8 Michael P. Busch,8#
and James C. Zimring9# for the Recipient Epidemiology and Donor Evaluation Study-III (REDS III)
1Department of Biochemistry and Molecular Genetics, University of Colorado Denver – Anschutz Medical Campus, Aurora, CO, USA; 2Department of Medicine – Division of Hematology, University of Colorado Denver – Anschutz Medical Campus, Aurora, CO, USA; 3Vitalant Research Institute (previously Blood Systems Research Institute), Denver, CO, USA; 4Bloodworks Northwest Research Institute, Seattle, WA, USA; 5University of Pittsburgh, Pittsburgh, PA, USA; 6RTI International, Atlanta, GA, USA; 7University of British Columbia, Victoria, Canada; 8Vitalant Research Institute (previously Blood Systems Research Institute), San Francisco, CA, USA and 9University of Virginia, Charlotesville, VA, USA
#MPB and JCZ contributed equally as co-senior authors
ABSTRACT
Red blood cell (RBC) storage in the blood bank promotes the progres- sive accumulation of metabolic alterations that may ultimately impact the erythrocyte capacity to cope with oxidant stressors. However, the metabolic underpinnings of the capacity of RBC to resist oxidant stress and the potential impact of donor biology on this phenotype are not known. Within the framework of the REDS-III RBC-Omics study, RBC from 8,502 healthy blood donors were stored for 42 days and tested for their propensity to hemolyse following oxidant stress. A subset of extreme hemolysers donated a second unit of blood, which was stored for 10, 23, and 42 days and profiled again for oxidative hemolysis and metabolomics (599 samples). Alterations of RBC energy and redox homeostasis were noted in donors with high oxidative hemolysis. RBC from females, donors over 60 years old, donors of Asian/South Asian race-ethnicity, and RBC stored in additive solu- tion-3 were each independently characterized by improved antioxidant metabolism compared to, respectively, males, donors under 30 years old, Hispanic and African American race ethnicity donors, and RBC stored in additive solution-1. Merging metabolomics data with results from an inde- pendent genome-wide association study on the same cohort, we identified metabolic markers of hemolysis and glucose 6-phosphate dehydrogenase- deficiency, which were associated with extremes in oxidative hemolysis and dysregulation in nicotinamide adenine dinucleotide phosphate and glu- tathione-dependent detoxification pathways of oxidized lipids. Donor sex, age, ethnicity, additive solution and glucose 6-phosphate dehydrogenase sta- tus impact the metabolism of the stored erythrocyte and its susceptibility to hemolysis following oxidative insults.
Introduction
Over the past decade the application of Omics Technologies1 to the field of red blood cell (RBC) storage has exponentially expanded our understanding of the temporal sequence and mechanisms of the storage lesion. Indeed, while refrigerat- ed storage in the blood bank is a logistic necessity to make ~110 million units
Correspondence:
ANGELO D’ALESSANDRO
angelo.dalessandro@ucdenver.edu
Received: January 7, 2020. Accepted: March 27, 2020. Pre-published: April 2, 2020.
https://doi.org/10.3324/haematol.2020.246603
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