{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:40:42Z","timestamp":1777398042344,"version":"3.51.4"},"reference-count":48,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["F32GM124599"],"award-info":[{"award-number":["F32GM124599"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["75N2019D00033"],"award-info":[{"award-number":["75N2019D00033"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["HemaSphere"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Sickle cell trait (SCT), the heterozygous state for the hemoglobin S (HbS) mutation, affects roughly 1 in 13 African American individuals and is common among blood donors recruited for antigen\u2010matched transfusions in sickle cell disease (SCD). While individuals with SCT are typically asymptomatic, it is unclear whether red blood cells (RBCs) from SCT donors have impaired storage quality and transfusion efficacy. Here, we integrate multi\u2010omics to characterize RBCs from donors SCT and evaluate their performance post\u2010transfusion. We first profiled RBCs from 174 HbAS and 248 HbAA volunteers, identifying elevated levels of metabolic markers of the storage lesion in SCT RBCs at baseline. We then interrogated the REDS RBC Omics dataset (&gt;13,000 donors), identifying blood donors carrying the HbS E6V variants. SCT RBCs exhibited accelerated metabolic aging, oxidative stress, and proteostatic activation\u2014phenotypes further exacerbated by storage duration and co\u2010inheritance of G6PD deficiency. Functional assays confirmed decreased osmotic fragility and increased oxidative hemolysis in SCT RBCs by storage Day 42. Pre\u2010clinically, stored RBCs from Townes mice carrying one allele of human sickle hemoglobin were characterized by a drop in post\u2010transfusion recovery compared to mice expressing canonical human hemoglobin. Clinically, analysis of 6828 transfusion events revealed that SCT RBCs were associated with lower hemoglobin increments 24\u2009h post\u2010transfusion. These findings provide mechanistic and clinical evidence that SCT influences RBC quality and transfusion outcomes. Given the overrepresentation of SCT in donor pools serving patients with SCD, our study supports a more personalized approach to inventory management and transfusion strategies in high\u2010risk populations.<\/jats:p>","DOI":"10.1002\/hem3.70360","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T12:17:06Z","timestamp":1776169026000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lower efficacy of transfusion of red blood cells from donors with sickle cell trait"],"prefix":"10.1002","volume":"10","author":[{"given":"Monika","family":"Dzieciatkowska","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics University of Colorado Denver \u2013 Anschutz Medical Campus Aurora Colorado USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Stephenson","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics University of Colorado Denver \u2013 Anschutz Medical Campus Aurora Colorado USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ariel","family":"Hay","sequence":"additional","affiliation":[{"name":"University of Virginia Charlottesville Virginia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xunde","family":"Wang","sequence":"additional","affiliation":[{"name":"Sickle Cell Branch, National Heart Lung, and Blood Institute, NIH Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory R.","family":"Keele","sequence":"additional","affiliation":[{"name":"RTI International Research Triangle Park North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Travis","family":"Nemkov","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics University of Colorado Denver \u2013 Anschutz Medical Campus Aurora Colorado 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USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steve","family":"Kleinman","sequence":"additional","affiliation":[{"name":"University of British Columbia Vancouver British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip J.","family":"Norris","sequence":"additional","affiliation":[{"name":"Vitalant Research Institute San Francisco California USA"},{"name":"Department of Laboratory Medicine University of California San Francisco San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael P.","family":"Busch","sequence":"additional","affiliation":[{"name":"Vitalant Research Institute San Francisco California USA"},{"name":"Department of Laboratory Medicine University of California San Francisco San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grier P.","family":"Page","sequence":"additional","affiliation":[{"name":"RTI International Research Triangle Park North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven L.","family":"Spitalnik","sequence":"additional","affiliation":[{"name":"Laboratory of Transfusion Biology, Department of Pathology and Cell Biology Columbia University New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nareg","family":"Roubinian","sequence":"additional","affiliation":[{"name":"Vitalant Research Institute San Francisco California USA"},{"name":"Department of Laboratory Medicine University of California San Francisco San Francisco California USA"},{"name":"Kaiser Permanente Northern California Division of Research Oakland California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James C.","family":"Zimring","sequence":"additional","affiliation":[{"name":"University of British Columbia Vancouver British Columbia Canada"},{"name":"Canadian Blood Services Vancouver British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Swee\u2010Lay","family":"Thein","sequence":"additional","affiliation":[{"name":"Sickle Cell Branch, National Heart Lung, and Blood Institute, NIH Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2258-6490","authenticated-orcid":false,"given":"Angelo","family":"D'Alessandro","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics University of Colorado Denver \u2013 Anschutz Medical Campus Aurora Colorado USA"},{"name":"Omix Technologies Inc Aurora Colorado USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,14]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61229-X"},{"issue":"49","key":"e_1_2_10_3_1","first-page":"1155","article-title":"Incidence of sickle cell trait\u2014United States, 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blood cell storage lesion: causes and potential clinical consequences","volume":"17","author":"Yoshida T","year":"2019","journal-title":"Blood Transfus"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2020.273946"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2020.246603"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI133530"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019000944"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2115616120"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo13070793"},{"issue":"1","key":"e_1_2_10_29_1","first-page":"27","article-title":"Red cell proteasome modulation by storage, redox metabolism and transfusion","volume":"20","author":"Tzounakas VL","year":"2022","journal-title":"Blood 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