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

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

Author information

1
Center for Biomedicine, European Academy of Bozen/Bolzano, Bolzano, Italy;
2
Department of Biochemistry and Molecular Genetics, University of Colorado Denver School of Medicine, University of Colorado Denver, Aurora, CO;
3
Center for Systems Biology, University of Iceland, Reykjavik, Iceland;
4
The Blood Bank, Landspitali-University Hospital, Reykjavik, Iceland; School of Science and Engineering, Reykjavik Unversity, Reykajvik, Iceland; and.
5
Sinopia Biosciences, San Diego, CA.
6
Center for Systems Biology, University of Iceland, Reykjavik, Iceland; Sinopia Biosciences, San Diego, CA.
7
The Blood Bank, Landspitali-University Hospital, Reykjavik, Iceland;

Abstract

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.

PMID:
27554084
DOI:
10.1182/blood-2016-06-721688
[Indexed for MEDLINE]

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