Effects of Storage Time on Glycolysis in Donated Human Blood Units

Abstract

Background: Donated blood is typically stored before transfusions. During storage, the metabolism of red blood cells changes, possibly causing storage lesions. The changes are storage time dependent and exhibit donor-specific variations. It is necessary to uncover and characterize the responsible molecular mechanisms accounting for such biochemical changes, qualitatively and quantitatively; Study Design and Methods: Based on the integration of metabolic time series data, kinetic models, and a stoichiometric model of the glycolytic pathway, a customized inference method was developed and used to quantify the dynamic changes in glycolytic fluxes during the storage of donated blood units. The method provides a proof of principle for the feasibility of inferences regarding flux characteristics from metabolomics data; Results: Several glycolytic reaction steps change substantially during storage time and vary among different fluxes and donors. The quantification of these storage time effects, which are possibly irreversible, allows for predictions of the transfusion outcome of individual blood units; Conclusion: The improved mechanistic understanding of blood storage, obtained from this computational study, may aid the identification of blood units that age quickly or more slowly during storage, and may ultimately improve transfusion management in clinics.

An Insight into the Stages of Ion Leakage during Red Blood Cell Storage

“…As had previously been reported [ 38 , 39 ] and confirmed in this work, lactate level significantly increases with the time of storage ( Figure 1 F), while the glucose level decreases ( Table S3 ). Such changes in glucose and lactate (resulting from glycolysis) systematically continue to occur in pRBCs during the whole time of storage.…”

Restoration of Physiological Levels of Uric Acid and Ascorbic Acid Reroutes the Metabolism of Stored Red Blood Cells

“…The rates of extracellular glucose consumption and lactate accumulation were higher at the beginning of the storage, suggesting a more active glycolysis [16,30,32] (Figures 3A and 3B). The antioxidant treatment did not impact these kinetics.…”