title: Routine storage of red blood cell (RBC) units in additive solution-3: a comprehensive investigation of the RBC metabolome.
abstract: BACKGROUND
  In most countries, red blood cells (RBCs) can be stored up to 42 days before transfusion. However, observational studies have suggested that storage duration might be associated with increased morbidity and mortality. While clinical trials are under way, impaired metabolism has been documented in RBCs stored in several additive solutions (ASs). Here we hypothesize that, despite reported beneficial effects, storage in AS-3 results in metabolic impairment weeks before the end of the unit shelf life.
  
  
  METHODS
  Five leukofiltered AS-3 RBC units were sampled before, during, and after leukoreduction Day 0 and then assayed on a weekly basis from storage Day 1 through Day 42. RBC extracts and supernatants were assayed using a ultra-high-performance liquid chromatography separations coupled online with mass spectrometry detection metabolomics workflow.
  
  
  RESULTS
  Blood bank storage significantly affects metabolic profiles of RBC extracts and supernatants by Day 14. In addition to energy and redox metabolism impairment, intra- and extracellular accumulation of amino acids was observed proportionally to storage duration, suggesting a role for glutamine and serine metabolism in aging RBCs.
  
  
  CONCLUSIONS
  Metabolomics of stored RBCs could drive the introduction of alternative ASs to address some of the storage-dependent metabolic lesions herein reported, thereby increasing the quality of transfused RBCs and minimizing potential links to patient morbidity.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Colorado Denver-Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Angelo
authors.initials: A
authors.lastname: D'Alessandro
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Colorado Denver-Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Travis
authors.initials: T
authors.lastname: Nemkov
authors.affiliation: Research Laboratory, Bonfils Blood Center, Denver, Colorado.
authors.forename: Marguerite
authors.initials: M
authors.lastname: Kelher
authors.affiliation: Clinical Services, Bonfils Blood Center, Denver, Colorado.
authors.forename: F Bernadette
authors.initials: FB
authors.lastname: West
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Colorado Denver-Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Rani K
authors.initials: RK
authors.lastname: Schwindt
authors.affiliation: Department of Surgery, University of Colorado Denver-Anschutz Medical Campus, Aurora, Colorado.|Denver Health Medical Center, Denver, Colorado.
authors.forename: Anirban
authors.initials: A
authors.lastname: Banerjee
authors.affiliation: Department of Surgery, University of Colorado Denver-Anschutz Medical Campus, Aurora, Colorado.|Denver Health Medical Center, Denver, Colorado.
authors.forename: Ernest E
authors.initials: EE
authors.lastname: Moore
authors.affiliation: Department of Surgery, University of Colorado Denver-Anschutz Medical Campus, Aurora, Colorado.|Department of Pediatrics, University of Colorado Denver-Anschutz Medical Campus, Aurora, Colorado.|Research Laboratory, Bonfils Blood Center, Denver, Colorado.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Silliman
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Colorado Denver-Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Kirk C
authors.initials: KC
authors.lastname: Hansen
mesh_terms: D000225:Adenine / Q000494:pharmacology*; D000328:Adult; D001793:Blood Preservation; D002851:Chromatography, High Pressure Liquid; D002951:Citrates / Q000494:pharmacology*; D003080:Cold Temperature; D017707:Erythrocyte Transfusion; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007552:Isotonic Solutions / Q000494:pharmacology; D055442:Metabolome / Q000187:drug effects*; D019188:Organ Preservation Solutions / Q000494:pharmacology*; D010710:Phosphates / Q000494:pharmacology*; D012965:Sodium Chloride / Q000494:pharmacology*; D013997:Time Factors
chemical_list: C058647:AS-3 preservative solution; D002951:Citrates; D007552:Isotonic Solutions; D019188:Organ Preservation Solutions; D010710:Phosphates; D012965:Sodium Chloride; D005947:Glucose; D000225:Adenine