Metabolomics evaluation of early-storage red blood cell rejuvenation at 4°C and 37°C

Transfusion. 2018 Aug;58(8):1980-1991. doi: 10.1111/trf.14623. Epub 2018 Apr 24.


Background: Refrigerated red blood cell (RBC) storage results in the progressive accumulation of biochemical and morphological alterations collectively referred to as the storage lesion. Storage-induced metabolic alterations can be in part reversed by rejuvenation practices. However, rejuvenation requires an incubation step of RBCs for 1 hour at 37°C, limiting the practicality of providing "on-demand," rejuvenated RBCs. We tested the hypothesis that the addition of rejuvenation solution early in storage as an adjunct additive solution would prevent-in a time window consistent with the average age of units transfused to sickle cell recipients at Duke (15 days)-many of the adverse biochemical changes that can be reversed via standard rejuvenation, while obviating the incubation step.

Study design and methods: Metabolomics analyses were performed on cells and supernatants from AS-1 RBC units (n = 4), stored for 15 days. Units were split into pediatric bag aliquots and stored at 4°C. These were untreated controls, washed with or without rejuvenation, performed under either standard (37°C) or cold (4°C) conditions.

Results: All three treatments removed most metabolic storage by-products from RBC supernatants. However, only standard and cold rejuvenation provided significant metabolic benefits as judged by the reactivation of glycolysis and regeneration of adenosine triphosphate and 2,3-diphosphoglycerate. Improvements in energy metabolism also translated into increased capacity to restore the total glutathione pool and regenerate oxidized vitamin C in its reduced (ascorbate) form.

Conclusion: Cold and standard rejuvenation of 15-day-old RBCs primes energy and redox metabolism of stored RBCs, while providing a logistic advantage for routine blood bank processing workflows.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2,3-Diphosphoglycerate / metabolism
  • Adenosine Triphosphate / metabolism
  • Blood Banks / methods
  • Blood Preservation / methods*
  • Energy Metabolism
  • Erythrocytes / cytology*
  • Glycolysis
  • Humans
  • Metabolomics / methods*
  • Oxidation-Reduction
  • Rejuvenation*
  • Temperature*


  • 2,3-Diphosphoglycerate
  • Adenosine Triphosphate