Biomarkers defining the metabolic age of red blood cells during cold storage

Blood. 2016 Sep 29;128(13):e43-50. doi: 10.1182/blood-2016-06-721688. Epub 2016 Aug 23.


Metabolomic investigations of packed red blood cells (RBCs) stored under refrigerated conditions in saline adenine glucose mannitol (SAGM) additives have revealed the presence of 3 distinct metabolic phases, occurring on days 0-10, 10-18, and after day 18 of storage. Here we used receiving operating characteristics curve analysis to identify biomarkers that can differentiate between the 3 metabolic states. We first recruited 24 donors and analyzed 308 samples coming from RBC concentrates stored in SAGM and additive solution 3. We found that 8 extracellular compounds (lactic acid, nicotinamide, 5-oxoproline, xanthine, hypoxanthine, glucose, malic acid, and adenine) form the basis for an accurate classification/regression model and are able to differentiate among the metabolic phases. This model was then validated by analyzing an additional 49 samples obtained by preparing 7 new RBC concentrates in SAGM. Despite the technical variability associated with RBC processing strategies, verification of these markers was independently confirmed in 2 separate laboratories with different analytical setups and different sample sets. The 8 compounds proposed here highly correlate with the metabolic age of packed RBCs, and can be prospectively validated as biomarkers of the RBC metabolic lesion.

Publication types

  • Validation Study

MeSH terms

  • Adult
  • Biomarkers / blood*
  • Blood Preservation / methods*
  • Cold Temperature
  • Erythrocyte Aging / physiology
  • Erythrocytes / cytology*
  • Erythrocytes / metabolism*
  • Female
  • Humans
  • In Vitro Techniques
  • Male
  • Metabolome
  • Middle Aged
  • Models, Biological
  • Prospective Studies
  • Regression Analysis
  • Time Factors
  • Young Adult


  • Biomarkers