title: Metabolomics of ADSOL (AS-1) red blood cell storage.
abstract: Population-based investigations suggest that red blood cells (RBCs) are therapeutically effective when collected, processed, and stored for up to 42 days under validated conditions before transfusion. However, some retrospective clinical studies have shown worse patient outcomes when transfused RBCs have been stored for the longest times. Furthermore, studies of RBC persistence in the circulation after transfusion have suggested that considerable donor-to-donor variability exists and may affect transfusion efficacy. To understand the limitations of current blood storage technologies and to develop approaches to improve RBC storage and transfusion efficacy, we investigated the global metabolic alterations that occur when RBCs are stored in AS-1 (AS1-RBC). Leukoreduced AS1-RBC units prepared from 9 volunteer research donors (12 total donated units) were serially sampled for metabolomics analysis over 42 days of refrigerated storage. Samples were tested by gas chromatography/mass spectrometry and liquid chromatography/tandem mass spectrometry, and specific biochemical compounds were identified by comparison to a library of purified standards. Over 3 experiments, 185 to 264 defined metabolites were quantified in stored RBC samples. Kinetic changes in these biochemicals confirmed known alterations in glycolysis and other pathways previously identified in RBCs stored in saline, adenine, glucose and mannitol solution (SAGM-RBC). Furthermore, we identified additional alterations not previously seen in SAGM-RBCs (eg, stable pentose phosphate pathway flux, progressive decreases in oxidized glutathione), and we delineated changes occurring in other metabolic pathways not previously studied (eg, S-adenosyl methionine cycle). These data are presented in the context of a detailed comparison with previous studies of SAGM-RBCs from human donors and murine AS1-RBCs. Global metabolic profiling of AS1-RBCs revealed a number of biochemical alterations in stored blood that may affect RBC viability during storage as well as therapeutic effectiveness of stored RBCs in transfusion recipients. These results provide future opportunities to more clearly pinpoint the metabolic defects during RBC storage, to identify biomarkers for donor screening and prerelease RBC testing, and to develop improved RBC storage solutions and methodologies.
authors.affiliation: Center for Transfusion and Cellular Therapies, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA. Electronic address: jroback@emory.edu.
authors.forename: John D
authors.initials: JD
authors.lastname: Roback
authors.affiliation: Center for Transfusion and Cellular Therapies, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA.
authors.forename: Cassandra D
authors.initials: CD
authors.lastname: Josephson
authors.affiliation: Center for Transfusion and Cellular Therapies, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA; Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA.
authors.forename: Edmund K
authors.initials: EK
authors.lastname: Waller
authors.affiliation: Center for Transfusion and Cellular Therapies, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA.
authors.forename: James L
authors.initials: JL
authors.lastname: Newman
authors.affiliation: Center for Transfusion and Cellular Therapies, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA.
authors.forename: Sulaiman
authors.initials: S
authors.lastname: Karatela
authors.affiliation: Department of Medicine, Emory University School of Medicine, Atlanta, GA.
authors.forename: Karan
authors.initials: K
authors.lastname: Uppal
authors.affiliation: Department of Medicine, Emory University School of Medicine, Atlanta, GA.
authors.forename: Dean P
authors.initials: DP
authors.lastname: Jones
authors.affiliation: Puget Sound Blood Center Research Institute, Seattle, WA.
authors.forename: James C
authors.initials: JC
authors.lastname: Zimring
authors.affiliation: Geisel School of Medicine at Dartmouth, Lebanon, NH.
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Dumont
mesh_terms: D000225:Adenine / Q000737:chemistry*; D000818:Animals; D001793:Blood Preservation / Q000379:methods*; D002462:Cell Membrane / Q000378:metabolism; D002853:Chromatography, Liquid; D017707:Erythrocyte Transfusion / Q000379:methods; D004912:Erythrocytes / Q000166:cytology*; D008401:Gas Chromatography-Mass Spectrometry; D005947:Glucose / Q000737:chemistry*; D006019:Glycolysis; D006801:Humans; D007700:Kinetics; D008055:Lipids / Q000737:chemistry; D008353:Mannitol / Q000737:chemistry*; D055442:Metabolome; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D015398:Signal Transduction; D012965:Sodium Chloride / Q000737:chemistry*; D053719:Tandem Mass Spectrometry
chemical_list: C037839:ADSOL; D008055:Lipids; D008353:Mannitol; D012965:Sodium Chloride; D005947:Glucose; D000225:Adenine