Background/Case Studies: Stored red blood cells (RBCs) undergo various modifications that impair their function, collectively referred to as storage lesions. Available glucose is used as a substrate for the production of ATP and NADPH, serving as energy and reducing power sources, respectively. These lesions include alterations in the redox state of the cells, increased production of reactive oxygen species (ROS), and weakening of antioxidant defenses. In circulation, oxidative damage arises from hemoglobin autooxidation, extracellular agents such as the vascular endothelium, and the inflammatory context.
Study
Design/Methods: We propose that residual leukocytes in the leukoreduced (LR) or non-leukoreduced (NLR) blood units exacerbate oxidative stress during storage. We analyzed the impact of pre-storage leukoreduction compared to non-leukoreduced units on various metabolites affected during storage. Glucose concentration was quantified using the Cobas 6000 analyzer (Roche), ATP was measured by a luminescence-based assay, and NADPH via an enzymatic cycling method.
Results/Findings: A decrease in glucose and ATP concentrations was observed with increasing storage time; however, no significant differences were found between NLR and LR units on day 42 in terms of glucose (NLR 198 ± 37 vs 176 ± 52 mg/dL n=7) and ATP levels (NLR 71 ± 10 µM vs. LR 77 ± 43 µM, n=4). Regarding NADPH quantification, no significant differences were detected between NLR and LR units on day 42 (NLR 14 ± 5 µM vs. LR 14 ± 7 µM, n=4), nor in the NADPH/NADPtotal ratio (NLR 0.69 ± 0.09 vs. LR 0.67 ± 0.15, n=4).
Conclusions: The decline in glucose concentration available for glycolysis may explain the reduction in ATP levels, as glucose is diverted toward NADPH production to sustain reducing power, maintaining its concentration throughout storage. The presence of leukocytes in the leukocyte-depleted blood unit does not appear to significantly impact redox balance, though it may limit ATP production, which is vital for erythrocyte functions. These results are relevant for public health policy decision-making and contribute to the discussion on selective versus universal leukoreduction strategies. Furthermore, they underscore the importance of continued research on the effects of oxidative stress on the metabolic pathways of red blood cells, particularly the pentose phosphate pathway, a key source of NADPH.
