title: Metabolic pathways that correlate with post-transfusion circulation of stored murine red blood cells.
abstract: Transfusion of red blood cells is a very common inpatient procedure, with more than 1 in 70 people in the USA receiving a red blood cell transfusion annually. However, stored red blood cells are a non-uniform product, based upon donor-to-donor variation in red blood cell storage biology. While thousands of biological parameters change in red blood cells over storage, it has remained unclear which changes correlate with function of the red blood cells, as opposed to being co-incidental changes. In the current report, a murine model of red blood cell storage/transfusion is applied across 13 genetically distinct mouse strains and combined with high resolution metabolomics to identify metabolic changes that correlated with red blood cell circulation post storage. Oxidation in general, and peroxidation of lipids in particular, emerged as changes that correlated with extreme statistical significance, including generation of dicarboxylic acids and monohydroxy fatty acids. In addition, differences in anti-oxidant pathways known to regulate oxidative stress on lipid membranes were identified. Finally, metabolites were identified that differed at the time the blood was harvested, and predict how the red blood cells perform after storage, allowing the potential to screen donors at time of collection. Together, these findings map out a new landscape in understanding metabolic changes during red blood cell storage as they relate to red blood cell circulation.
authors.affiliation: Bloodworks NW Research Institute, Seattle, WA, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: de Wolski
authors.affiliation: Bloodworks NW Research Institute, Seattle, WA, USA University of Washington Department of Internal Medicine, Division of Hematology, Seattle, WA, USA.
authors.forename: Xiaoyoun
authors.initials: X
authors.lastname: Fu
authors.affiliation: Geisel School of Medicine at Dartmouth, Lebanon.
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Dumont
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Roback
authors.affiliation: Bloodworks NW Research Institute, Seattle, WA, USA.
authors.forename: Hayley
authors.initials: H
authors.lastname: Waterman
authors.affiliation: Bloodworks NW Research Institute, Seattle, WA, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Odem-Davis
authors.affiliation: Bloodworks NW Research Institute, Seattle, WA, USA.
authors.forename: Heather L
authors.initials: HL
authors.lastname: Howie
authors.affiliation: Bloodworks NW Research Institute, Seattle, WA, USA University of Washington Department of Internal Medicine, Division of Hematology, Seattle, WA, USA University of Washington Department of Laboratory Medicine and Department of Internal Medicine, Division of Hematology, Seattle, WA, USA jzimring@BloodworksNW.org.
authors.forename: James C
authors.initials: JC
authors.lastname: Zimring
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001793:Blood Preservation / Q000009:adverse effects; D001803:Blood Transfusion; D017707:Erythrocyte Transfusion; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D056726:Genetic Association Studies; D005947:Glucose / Q000378:metabolism; D008297:Male; D053858:Metabolic Networks and Pathways; D055442:Metabolome; D055432:Metabolomics / Q000379:methods; D051379:Mice; D008815:Mice, Inbred Strains; D010084:Oxidation-Reduction; D013045:Species Specificity; D013997:Time Factors
chemical_list: D000975:Antioxidants; D005947:Glucose