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dc.contributor.authorBordbar, Aarash
dc.contributor.authorJohansson, Pär I.
dc.contributor.authorPaglia, Giuseppe
dc.contributor.authorHarrison, Scott J.
dc.contributor.authorWichuk, Kristine
dc.contributor.authorMagnusdottir, Manuela
dc.contributor.authorValgeirsdottir, Sóley
dc.contributor.authorGybel-Brask, Mikkel
dc.contributor.authorOstrowski, Sisse R.
dc.contributor.authorPalsson, Sirus
dc.contributor.authorRolfsson, Ottar
dc.contributor.authorSigurjónsson, Olafur E.
dc.contributor.authorHansen, Morten B.
dc.contributor.authorGudmundsson, Sveinn
dc.contributor.authorPalsson, Bernhard O.
dc.date.accessioned2016-05-30T11:50:44Zen
dc.date.available2016-05-30T11:50:44Zen
dc.date.issued2016-04en
dc.date.submitted2016en
dc.identifier.citationIdentified metabolic signature for assessing red blood cell unit quality is associated with endothelial damage markers and clinical outcomes 2016, 56 (4):852 Transfusionen
dc.identifier.issn00411132en
dc.identifier.doi10.1111/trf.13460en
dc.identifier.urihttp://hdl.handle.net/2336/611192en
dc.descriptionTo access publisher's full text version of this article click on the hyperlink at the bottom of the pageen
dc.description.abstractBACKGROUNDThere has been interest in determining whether older red blood cell (RBC) units have negative clinical effects. Numerous observational studies have shown that older RBC units are an independent factor for patient mortality. However, recently published randomized clinical trials have shown no difference of clinical outcome for patients receiving old or fresh RBCs. An overlooked but essential issue in assessing RBC unit quality and ultimately designing the necessary clinical trials is a metric for what constitutes an old or fresh RBC unit. STUDY DESIGN AND METHODSTwenty RBC units were profiled using quantitative metabolomics over 42 days of storage in SAGM with 3- to 4-day time intervals. Metabolic pathway usage during storage was assessed using systems biology methods. The detected time intervals of the metabolic states were compared to clinical outcomes. RESULTSUsing multivariate statistics, we identified a nonlinear decay process exhibiting three distinct metabolic states (Days 0-10, 10-17, and 17-42). Hematologic variables traditionally measured in the transfusion setting (e.g., pH, hemolysis, RBC indices) did not distinguish these three states. Systemic changes in pathway usage occurred between the three states, with key pathways changing in both magnitude and direction. Finally, an association was found between the time periods of the metabolic states with the clinical outcomes of more than 280,000 patients in the country of Denmark transfused over the past 15 years and endothelial damage markers in healthy volunteers undergoing autologous transfusions. CONCLUSIONThe state of RBC metabolism may be a better indicator of cellular quality than traditional hematologic variables.
dc.description.sponsorshipinfo:eu-repo/grantAgreement/EC/FP7/232816 National Heart, Lung and Blood Institute/R43HL123074en
dc.language.isoenen
dc.publisherWiley-Blackwellen
dc.relation.urlhttp://doi.wiley.com/10.1111/trf.13460en
dc.relation.urlhttp://onlinelibrary.wiley.com/doi/10.1111/trf.13460/epdfen
dc.rightsArchived with thanks to Transfusionen
dc.subjectBlóðgjöfen
dc.subjectNAF12
dc.subjectBAB12
dc.subject.meshod Preservationen
dc.subject.meshErythrocyte Transfusionen
dc.subject.meshHospital Mortalityen
dc.subject.meshRisk Factorsen
dc.titleIdentified metabolic signature for assessing red blood cell unit quality is associated with endothelial damage markers and clinical outcomesen
dc.typeArticleen
dc.contributor.department[ 1 ] Sinopia Biosci, 600 West Broadway Suite 700, San Diego, CA 92101 USA [ 2 ] Univ Copenhagen, Transfus Med Sect, Capital Reg Blood Bank, Rigshosp, DK-2100 Copenhagen, Denmark [ 3 ] Univ Iceland, Ctr Syst Biol, Reykjavik, Iceland [ 4 ] Tech Univ Denmark, Novo Nordisk Fdn Ctr Biosustainabil, DK-2800 Lyngby, Denmark [ 5 ] Landspitali Univ Hosp, Blood Bank, Reykjavik, Iceland   Organization-Enhanced Name(s)      Landspitali National University Hospital [ 6 ] Reykjavik Univ, Sch Sci & Engn, Reykjavik, Icelanden
dc.identifier.journalTransfusionen
dc.rights.accessNational Consortium - Landsaðganguren
dc.contributor.institutionSinopia Biosciences; San Diego Californiaen
dc.contributor.institutionSection for Transfusion Medicine, Capital Region Blood Bank, Rigshopitalet, University of Copenhagen; Copenhagen Denmarken
dc.contributor.institutionCenter for Systems Biology, University of Iceland; Reykjavik Icelanden
dc.contributor.institutionNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark; Lyngby Denmarken
dc.contributor.institutionCenter for Systems Biology, University of Iceland; Reykjavik Icelanden
dc.contributor.institutionCenter for Systems Biology, University of Iceland; Reykjavik Icelanden
dc.contributor.institutionCenter for Systems Biology, University of Iceland; Reykjavik Icelanden
dc.contributor.institutionSection for Transfusion Medicine, Capital Region Blood Bank, Rigshopitalet, University of Copenhagen; Copenhagen Denmarken
dc.contributor.institutionSection for Transfusion Medicine, Capital Region Blood Bank, Rigshopitalet, University of Copenhagen; Copenhagen Denmarken
dc.contributor.institutionSinopia Biosciences; San Diego Californiaen
dc.contributor.institutionCenter for Systems Biology, University of Iceland; Reykjavik Icelanden
dc.contributor.institutionBlood Bank, Landspitali-University Hospitalen
dc.contributor.institutionSection for Transfusion Medicine, Capital Region Blood Bank, Rigshopitalet, University of Copenhagen; Copenhagen Denmarken
dc.contributor.institutionBlood Bank, Landspitali-University Hospitalen
dc.contributor.institutionCenter for Systems Biology, University of Iceland; Reykjavik Icelanden
html.description.abstractBACKGROUNDThere has been interest in determining whether older red blood cell (RBC) units have negative clinical effects. Numerous observational studies have shown that older RBC units are an independent factor for patient mortality. However, recently published randomized clinical trials have shown no difference of clinical outcome for patients receiving old or fresh RBCs. An overlooked but essential issue in assessing RBC unit quality and ultimately designing the necessary clinical trials is a metric for what constitutes an old or fresh RBC unit. STUDY DESIGN AND METHODSTwenty RBC units were profiled using quantitative metabolomics over 42 days of storage in SAGM with 3- to 4-day time intervals. Metabolic pathway usage during storage was assessed using systems biology methods. The detected time intervals of the metabolic states were compared to clinical outcomes. RESULTSUsing multivariate statistics, we identified a nonlinear decay process exhibiting three distinct metabolic states (Days 0-10, 10-17, and 17-42). Hematologic variables traditionally measured in the transfusion setting (e.g., pH, hemolysis, RBC indices) did not distinguish these three states. Systemic changes in pathway usage occurred between the three states, with key pathways changing in both magnitude and direction. Finally, an association was found between the time periods of the metabolic states with the clinical outcomes of more than 280,000 patients in the country of Denmark transfused over the past 15 years and endothelial damage markers in healthy volunteers undergoing autologous transfusions. CONCLUSIONThe state of RBC metabolism may be a better indicator of cellular quality than traditional hematologic variables.


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