{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T11:25:27Z","timestamp":1767007527786,"version":"3.40.5"},"reference-count":31,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T00:00:00Z","timestamp":1633910400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100001458","name":"American Kennel Club Canine Health Foundation","doi-asserted-by":"publisher","award":["01988"],"award-info":[{"award-number":["01988"]}],"id":[{"id":"10.13039\/100001458","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Transfusion"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Transfusion of red blood cells (RBCs) stored for longer durations induces hemolysis and inflammatory cytokine production in murine and canine models. Despite immune system activation by stored RBCs, human randomized trials suggest that fresher RBC transfusions do not improve clinical outcomes. We hypothesized that underlying recipient hemolysis may affect cytokine responses to older RBC transfusions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study design and methods<\/jats:title><jats:p>C57BL\/6 mouse cohorts were infused with anti\u2010TER119 antibody to induce hemolysis, rabbit anti\u2010platelet antiserum to induce immune thrombocytopenia (ITP), or appropriate control antibodies. Two days later, mice were transfused with fresh or stored RBCs. Furthermore, in a prospective, randomized, blinded trial, 38 client\u2010owned dogs with primary autoimmune hemolytic anemia (AIHA) and two dogs with ITP, requiring RBC transfusion, were enrolled and randomized to receive fresh (\u22647\u2009days) or old (\u226521\u2009days) stored RBC transfusions. Monocyte chemoattractant protein (MCP)\u20101 levels were assessed at defined times after transfusion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Prior immune\u2010mediated hemolysis blunted the MCP\u20101 response to stored RBC transfusion in mice (361\u2009\u00b1\u2009111\u2009pg\/ml vs. 6836\u2009\u00b1\u20091528\u2009pg\/ml in mice with immune hemolysis vs. ITP, respectively; mean\u2009\u00b1\u2009SD; <jats:italic>p<\/jats:italic>\u00a0&lt;\u2009.0001). Although hemolysis markers increased after transfusion of older RBCs, the cytokine response was also muted in dogs with AIHA. No differences in morbidity or mortality were evident comparing dogs randomized to fresh or old RBCs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These data suggest that underlying hemolysis blunts inflammatory responses to old RBC transfusions. The canine data support randomized trial results suggesting a lack of clinical benefit with fresh RBC transfusions in subjects with underlying, baseline hemolysis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/trf.16690","type":"journal-article","created":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T12:42:09Z","timestamp":1634128929000},"page":"3309-3319","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Hemolytic anemia blunts the cytokine response to transfusion of older red blood cells in mice and dogs"],"prefix":"10.1111","volume":"61","author":[{"given":"Mary Beth","family":"Callan","sequence":"first","affiliation":[{"name":"Department of Clinical Sciences and Advanced Medicine University of Pennsylvania School of Veterinary Medicine  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent J.","family":"Thawley","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Advanced Medicine University of Pennsylvania School of Veterinary Medicine  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimberly A.","family":"Marryott","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Advanced Medicine University of Pennsylvania School of Veterinary Medicine  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aidin","family":"Shabro","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cell Biology Columbia University Irving Medical Center \u2013 New York Presbyterian Hospital  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian","family":"Fernando","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cell Biology Columbia University Irving Medical Center \u2013 New York Presbyterian Hospital  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stacie","family":"Kahn","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Columbia University Irving Medical Center \u2013 New York Presbyterian Hospital  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5663-9290","authenticated-orcid":false,"given":"Krystalyn E.","family":"Hudson","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cell Biology Columbia University Irving Medical Center \u2013 New York Presbyterian Hospital  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2367-9509","authenticated-orcid":false,"given":"Eldad A.","family":"Hod","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cell Biology Columbia University Irving Medical Center \u2013 New York Presbyterian Hospital  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,10,11]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1537-2995.2011.03511.x"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1537-2995.2008.01642.x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-11-567750"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.transci.2010.05.009"},{"key":"e_1_2_8_6_1","first-page":"112","article-title":"The controversy over the age of blood: what do the clinical trials really teach us?","volume":"15","author":"Belpulsi D","year":"2017","journal-title":"Blood 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