{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T10:43:48Z","timestamp":1790765028047,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,3,10]],"date-time":"2017-03-10T00:00:00Z","timestamp":1489104000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Citra Labs, LLC"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Transfusion"],"published-print":{"date-parts":[[2017,4]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Storage of red blood cells (RBCs) under blood bank conditions promotes metabolic modulation within the RBC. This \u201cmetabolic storage lesion\u201d may affect the quality and safety of the transfused RBCs. The aim of this study is to determine the metabolic changes in stored RBCs over 42 days of routine storage followed by a US Food and Drug Administration\u2010approved method of rejuvenation, freezing, and preparation for transfusion.<\/jats:p><\/jats:sec><jats:sec><jats:title>STUDY DESIGN AND METHODS<\/jats:title><jats:p>We exploited a mass spectrometry\u2010based metabolomics approach to monitor 42\u2010day\u2010stored citrate phosphate dextrose\/AS\u20101 RBCs (n\u2009=\u200929) that were rejuvenated, glycerolized and frozen, then thawed and deglycerolized, and held for 24 hours at 1 to 6\u00baC in saline\u2010glucose.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Previously reported metabolic alterations were confirmed in 42\u2010day\u2010old RBCs. In this study, in total, 181 (62%) of the biochemical compounds exhibited significant (p\u2009\u2264\u20090.05) change compared with Day 0 values. Rejuvenation restored adenosine triphosphate and 2,3\u2010diphosphoglycerate levels, replenished purine reservoirs, up regulated glycolysis, increased levels of pentose phosphate pathway intermediates, and partially rescued glutathione biosynthesis. Increased levels of lysophospholipid in rejuvenated RBCs suggests the activation of recycling pathways of damaged membrane lipids, in which a total of 167 (57%) biochemical compounds showed significant change compared with Day 42 values.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p>Rejuvenation reversed over one\u2010half of the metabolic biochemical compounds evaluated compared with Day 42 values, and the compounds were stable through frozen storage and preparation for transfusion. Rejuvenation promoted significant metabolic reprogramming, including the reactivation of energy\u2010generating and antioxidant pathways (the pentose phosphate pathway and glutathione homeostasis), salvage reactions, cofactor reservoirs, and membrane lipid recycling.<\/jats:p><\/jats:sec>","DOI":"10.1111\/trf.14034","type":"journal-article","created":{"date-parts":[[2017,3,10]],"date-time":"2017-03-10T17:32:04Z","timestamp":1489167124000},"page":"1019-1030","source":"Crossref","is-referenced-by-count":59,"title":["Red blood cell metabolic responses to refrigerated storage, rejuvenation, and frozen storage"],"prefix":"10.1111","volume":"57","author":[{"given":"Angelo","family":"D'Alessandro","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics University of Colorado Denver\u2013Anschutz Medical Campus Aurora Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan D.","family":"Gray","sequence":"additional","affiliation":[{"name":"Citra Labs Braintree Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zbigniew M.","family":"Szczepiorkowski","sequence":"additional","affiliation":[{"name":"Department of Pathology Geisel School of Medicine at Dartmouth  Lebanon New Hampshire"},{"name":"Institute of Hematology and Transfusion Medicine Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirk","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics University of Colorado Denver\u2013Anschutz Medical Campus Aurora Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise H.","family":"Herschel","sequence":"additional","affiliation":[{"name":"Institute of Hematology and Transfusion Medicine Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larry J.","family":"Dumont","sequence":"additional","affiliation":[{"name":"Department of Pathology Geisel School of Medicine at Dartmouth  Lebanon New Hampshire"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,3,10]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1423-0410.2006.00778.x"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/trf.13250"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/trf.12804"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/trf.13609"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2012.03.012"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2011.051789"},{"key":"e_1_2_8_8_1","first-page":"548","article-title":"Biochemical assessment of red blood cells during storage by (1)H nuclear magnetic resonance spectroscopy. 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