{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T01:50:28Z","timestamp":1793152228301,"version":"4.5.0"},"reference-count":50,"publisher":"American Society for Clinical Investigation","issue":"1","license":[{"start":{"date-parts":[[2022,1,11]],"date-time":"2022-01-11T00:00:00Z","timestamp":1641859200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"crossref","award":["HHSN 75N92019D00032,HHSN 75N92019D00034,HHSN 75N92019D00035,HHSN 75N92019D00036,HHSN 75N92019D00037,R01HL126130"],"award-info":[{"award-number":["HHSN 75N92019D00032,HHSN 75N92019D00034,HHSN 75N92019D00035,HHSN 75N92019D00036,HHSN 75N92019D00037,R01HL126130"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,1,11]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>RBC transfusion effectiveness varies due to donor, component, and recipient factors. Prior studies identified characteristics associated with variation in hemoglobin increments following transfusion. We extended these observations, examining donor genetic and nongenetic factors affecting transfusion effectiveness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>This is a multicenter retrospective study of 46,705 patients and 102,043 evaluable RBC transfusions from 2013 to 2016 across 12 hospitals. Transfusion effectiveness was defined as hemoglobin, bilirubin, or creatinine increments following single RBC unit transfusion. Models incorporated a subset of donors with data on single nucleotide polymorphisms associated with osmotic and oxidative hemolysis in vitro. Mixed modeling accounting for repeated transfusion episodes identified predictors of transfusion effectiveness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Blood donor (sex, Rh status, fingerstick hemoglobin, smoking), component (storage duration, \u03b3 irradiation, leukoreduction, apheresis collection, storage solution), and recipient (sex, BMI, race and ethnicity, age) characteristics were associated with hemoglobin and bilirubin, but not creatinine, increments following RBC transfusions. Increased storage duration was associated with increased bilirubin and decreased hemoglobin increments, suggestive of in vivo hemolysis following transfusion. Donor\n                      <jats:italic>G6PD<\/jats:italic>\n                      deficiency and polymorphisms in\n                      <jats:italic>SEC14L4<\/jats:italic>\n                      ,\n                      <jats:italic>HBA2<\/jats:italic>\n                      , and\n                      <jats:italic>MYO9B<\/jats:italic>\n                      genes were associated with decreased hemoglobin increments. Donor\n                      <jats:italic>G6PD<\/jats:italic>\n                      deficiency and polymorphisms in\n                      <jats:italic>SEC14L4<\/jats:italic>\n                      were associated with increased transfusion requirements in the subsequent 48 hours.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Donor genetic and other factors, such as RBC storage duration, affect transfusion effectiveness as defined by decreased hemoglobin or increased bilirubin increments. Addressing these factors will provide a precision medicine approach to improve patient outcomes, particularly for chronically transfused RBC recipients, who would most benefit from more effective transfusion products.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>FUNDING<\/jats:title>\n                    <jats:p>Funding was provided by HHSN 75N92019D00032, HHSN 75N92019D00034, 75N92019D00035, HHSN 75N92019D00036, and HHSN 75N92019D00037; R01HL126130; and the National Institute of Child Health and Human Development (NICHD).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1172\/jci.insight.152598","type":"journal-article","created":{"date-parts":[[2021,11,18]],"date-time":"2021-11-18T12:01:43Z","timestamp":1637236903000},"source":"Crossref","is-referenced-by-count":96,"title":["Donor genetic and nongenetic factors affecting red blood cell transfusion effectiveness"],"prefix":"10.1172","volume":"7","author":[{"given":"Nareg H.","family":"Roubinian","sequence":"first","affiliation":[{"name":"Division of Research, Kaiser Permanente Northern California, Oakland, California, USA."},{"name":"Vitalant Research Institute, San Francisco, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2127-1454","authenticated-orcid":true,"given":"Sarah E.","family":"Reese","sequence":"additional","affiliation":[{"name":"Westat, Rockville, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Qiao","sequence":"additional","affiliation":[{"name":"Westat, Rockville, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colleen","family":"Plimier","sequence":"additional","affiliation":[{"name":"Division of Research, Kaiser Permanente Northern California, Oakland, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9829-2934","authenticated-orcid":true,"given":"Fang","family":"Fang","sequence":"additional","affiliation":[{"name":"Division of Biostatistics and Epidemiology, RTI International, Durham, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2582-3786","authenticated-orcid":true,"given":"Grier P.","family":"Page","sequence":"additional","affiliation":[{"name":"Division of Biostatistics and Epidemiology, RTI International, Atlanta, Georgia, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ritchard G.","family":"Cable","sequence":"additional","affiliation":[{"name":"American Red Cross, Farmington, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6251-366X","authenticated-orcid":true,"given":"Brian","family":"Custer","sequence":"additional","affiliation":[{"name":"Vitalant Research Institute, San Francisco, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7267-9006","authenticated-orcid":true,"given":"Mark T.","family":"Gladwin","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9653-9905","authenticated-orcid":true,"given":"Ruchika","family":"Goel","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bob","family":"Harris","sequence":"additional","affiliation":[{"name":"Westat, Rockville, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7928-3132","authenticated-orcid":true,"given":"Jeanne E.","family":"Hendrickson","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Yale University, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6558-0913","authenticated-orcid":true,"given":"Tamir","family":"Kanias","sequence":"additional","affiliation":[{"name":"Vitalant Research Institute, Denver, Colorado, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1638-2969","authenticated-orcid":true,"given":"Steve","family":"Kleinman","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of British Columbia, Victoria, British Colombia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3740-0318","authenticated-orcid":true,"given":"Alan E.","family":"Mast","sequence":"additional","affiliation":[{"name":"Versiti Blood Research Institute, Milwaukee, Wisconsin, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0928-3436","authenticated-orcid":true,"given":"Steven R.","family":"Sloan","sequence":"additional","affiliation":[{"name":"Department of Pathology, Children\u2019s Hospital Boston, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9008-9154","authenticated-orcid":true,"given":"Bryan R.","family":"Spencer","sequence":"additional","affiliation":[{"name":"American Red Cross, Dedham, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8528-4561","authenticated-orcid":true,"given":"Steven L.","family":"Spitalnik","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1446-125X","authenticated-orcid":true,"given":"Michael P.","family":"Busch","sequence":"additional","affiliation":[{"name":"Vitalant Research Institute, San Francisco, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2367-9509","authenticated-orcid":true,"given":"Eldad A.","family":"Hod","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the National Heart Lung and Blood Institute (NHLBI) Recipient Epidemiology and Donor Evaluation Study IV Pediatrics (REDS-IV-P)","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2022,1,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019000773"},{"issue":"1","key":"B2","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1172\/JCI90837","article-title":"Prolonged red cell storage before transfusion increases extravascular hemolysis","volume":"127","author":"Rapido","year":"2017","journal-title":"J Clin Invest"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-11-567750"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1111\/trf.13609"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020008563"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1111\/trf.15310"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminhematol.2013.06.002"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1172\/JCI62972"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1111\/j.1537-2995.2008.01642.x"},{"issue":"6","key":"B10","first-page":"955","article-title":"Studies on the preservation of human blood. I. Variability in erythrocyte storage characteristics among healthy donors.","volume":"67","author":"Dern","year":"1966","journal-title":"J Lab Clin Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-08-371849"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1172\/JCI133530"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1111\/trf.13250"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2008.12.005"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019000944"},{"key":"B16","article-title":"Multi-ancestry genome-wide association study identifies 27 loci associated with erythrocyte osmotic fragility, oxidative or spontaneous hemolysis following blood storage","author":"Page","journal-title":"J Clin Invest"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1111\/voxs.12518"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.tmrv.2017.07.006"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1111\/trf.14971"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1111\/trf.15833"},{"issue":"2","key":"B21","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1046\/j.1423-0410.1997.7220101.x","article-title":"Evaluation of a new prestorage leukoreduction filter for red blood cell units","volume":"72","author":"AuBuchon","year":"1997","journal-title":"Vox Sang"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.transci.2005.11.006"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3390\/ijns5010016"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1046\/j.1537-2995.1992.32692367195.x"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1046\/j.1537-2995.1999.39299154725.x"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1172\/JCI106165"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-016-2757-0"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25051"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1111\/trf.15439"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1500704"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2019.17478"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1414219"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.13977"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1609014"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1111\/trf.15248"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.21317"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.2830420116"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-02-203323"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1111\/trf.14481"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1111\/vox.12112"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3148.2011.01127.x"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0018328"},{"issue":"6","key":"B43","first-page":"930","article-title":"The poststorage viability of glucose-6-phosphate dehydrogenase-deficient erythrocytes","volume":"75","author":"Orlina","year":"1970","journal-title":"J Lab Clin Med"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-11-327361"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1111\/j.1537-2995.2012.03765.x"},{"key":"B46","unstructured":"National Heart, Lung, and Blood Institute. Recipinet Epidemiology and Donor Evaluation Study III (REDS III) Vein to Vein Databases. https:\/\/biolincc.nhlbi.nih.gov\/studies\/reds_iii\/ Updated March 4, 2020. Accessed November 23, 2021"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1111\/trf.14370"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.jamcollsurg.2020.05.027"},{"issue":"1","key":"B49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v067.i01","article-title":"Fitting linear mixed-effects models using Ime4","volume":"67","author":"Bates","year":"2015","journal-title":"J Stat Softw"},{"key":"B50","unstructured":"R Core Team. Version 4.1.2. R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria; 2021. Accessed November 23, 2021. https:\/\/www.r-project.org\/"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/152598\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T23:40:14Z","timestamp":1779147614000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/152598"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,11]]},"references-count":50,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1,11]]},"published-print":{"date-parts":[[2022,1,11]]}},"alternative-id":["10.1172\/jci.insight.152598"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.152598","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,11]]},"article-number":"e152598"}}