title: Metabolomics comparison of red cells stored in four additive solutions reveals differences in citrate anticoagulant permeability and metabolism.
abstract: OBJECTIVE
  Metabolomics studies have revealed transition points in metabolic signatures of red cells during storage in SAGM, whose clinical significance is unclear. We set out to investigate whether these transition points occur independent of storage media and define differences in the metabolism of red cells in additive solutions.
  
  
  METHODS
  Red cell concentrates were stored in SAGM, AS-1, AS-3 or PAGGSM, and sampled fourteen times spanning Day 1-46. Following quality control, the samples were split into extracellular and intracellular aliquots. These were analysed with ultra-high-performance liquid chromatography coupled to mass spectrometry analysis affording quantitative metabolic profiles of both intra- and extracellular red cell metabolites.
  
  
  RESULTS
  Differences were observed in glycolysis, purine salvage, glutathione synthesis and citrate metabolism on account of the storage solutions. Donor variability however hindered the accurate characterization of metabolic transition time-points. Intracellular citrate concentrations were increased in red cells stored in AS-3 and PAGGSM media. The metabolism of citrate in red cells in SAGM was subsequently confirmed using13C citrate isotope labelling and shown to originate from citrate anticoagulant.
  
  
  CONCLUSIONS
  Metabolic signatures that discriminate between 'fresh' and 'old' stored red cells are dependent upon additive solutions. Specifically, the incorporation and metabolism of citrate in additive solutions with lower chloride ion concentration is altered and impacts glycolysis.
authors.affiliation: Center for Systems Biology, University of Iceland, Reykjavik, Iceland.|Medical Department, University of Iceland, Reykjavik, Iceland.
authors.forename: Ó
authors.identifier: http://orcid.org/0000-0003-4258-6057
authors.initials: Ó
authors.lastname: Rolfsson
authors.affiliation: The Blood Bank, Landspitali-University Hospital, Reykjavik, Iceland.|School of Science and Engineering, Reykjavik University, Reykjavik, Iceland.
authors.forename: Ó E
authors.initials: ÓE
authors.lastname: Sigurjonsson
authors.affiliation: Center for Systems Biology, University of Iceland, Reykjavik, Iceland.
authors.forename: M
authors.initials: M
authors.lastname: Magnusdottir
authors.affiliation: Center for Systems Biology, University of Iceland, Reykjavik, Iceland.|Medical Department, University of Iceland, Reykjavik, Iceland.
authors.forename: F
authors.initials: F
authors.lastname: Johannsson
authors.affiliation: Center for Systems Biology, University of Iceland, Reykjavik, Iceland.|Center for Biomedicine, European Academy of Bolzano/Bozen, Bolzano, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Paglia
authors.affiliation: Center for Systems Biology, University of Iceland, Reykjavik, Iceland.
authors.forename: S
authors.initials: S
authors.lastname: Guðmundsson
authors.affiliation: Sinopia Bioscience, San Diego, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Bordbar
authors.affiliation: Sinopia Bioscience, San Diego, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Palsson
authors.affiliation: Center for Systems Biology, University of Iceland, Reykjavik, Iceland.
authors.forename: S
authors.initials: S
authors.lastname: Brynjólfsson
authors.affiliation: The Blood Bank, Landspitali-University Hospital, Reykjavik, Iceland.
authors.forename: S
authors.initials: S
authors.lastname: Guðmundsson
authors.affiliation: Center for Systems Biology, University of Iceland, Reykjavik, Iceland.
authors.forename: B
authors.initials: B
authors.lastname: Palsson
mesh_terms: D000925:Anticoagulants / Q000378:metabolism; D001793:Blood Preservation / Q000379:methods*; D019343:Citric Acid / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D008297:Male; D055432:Metabolomics; D010539:Permeability; D012996:Solutions
chemical_list: D000925:Anticoagulants; D012996:Solutions; D019343:Citric Acid
keywords: SAGM; citrate; metabolomics; red cell storage; storage lesion