{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T17:42:33Z","timestamp":1791999753559,"version":"4.4.0"},"reference-count":17,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T00:00:00Z","timestamp":1624492800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Although both leukocytosis and leukopenia have been considered Systemic Inflammatory Response Syndrome criteria, leukopenia is not generally considered a normal response to infection. We sought to evaluate the prognostic validity of leukopenia as a sign of sepsis-defining hematological organ dysfunction within the Sepsis-3 framework. We hypothesized that leukopenia is associated with higher risk of mortality than leukocytosis among patients with suspected infection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a retrospective cohort study using the Medical Information Mart v1.4 in Intensive Care-III database. Multivariable regression models were used to evaluate the association between leukopenia and mortality in patients with suspected infection defined by Sepsis-3.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified 5,909 ICU patients with suspected infection; 250 (4.2%) had leukopenia. Leukopenia was associated with increased in-hospital mortality compared with leukocytosis (OR, 1.5; 95% CI 1.1\u20131.9). After adjusting for demographics and comorbidities in the Sepsis-3 consensus model, leukopenia remained associated with increased risk of mortality compared with leukocytosis (OR 1.6, 95% CI 1.2\u20132.2). Further adjustment for the platelet component of the SOFA attenuated the association between leukopenia and mortality (OR decreased from 1.5 to 1.1). However, 83 (1.4%) of patients had leukopenia without thrombocytopenia and 14 had leukopenia prior to thrombocytopenia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Among ICU patients with suspected infection, leukopenia was associated with increased risk of death compared with leukocytosis. Due to correlation with thrombocytopenia, leukopenia did not independently improve the prognostic validity of SOFA; however, leukopenia may present as a sign of sepsis prior to thrombocytopenia in a small subset of patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0252206","type":"journal-article","created":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T13:29:24Z","timestamp":1624541364000},"page":"e0252206","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":64,"title":["Evaluation of leukopenia during sepsis as a marker of sepsis-defining organ dysfunction"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9461-7022","authenticated-orcid":true,"given":"Samuel H.","family":"Belok","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7161-5254","authenticated-orcid":true,"given":"Nicholas A.","family":"Bosch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth S.","family":"Klings","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan J.","family":"Walkey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,6,24]]},"reference":[{"key":"pone.0252206.ref001","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)","volume":"315","author":"M Singer","year":"2016","journal-title":"JAMA"},{"key":"pone.0252206.ref002","doi-asserted-by":"crossref","first-page":"1644","DOI":"10.1378\/chest.101.6.1644","article-title":"Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis","volume":"101","author":"RC Bone","year":"1992","journal-title":"Chest"},{"key":"pone.0252206.ref003","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1164\/rccm.201502-0275OC","article-title":"Incidence and prognostic value of the systemic inflammatory response syndrome and organ dysfunctions in ward patients","volume":"192","author":"MM Churpek","year":"2015","journal-title":"Am J Respir Crit Care Med"},{"key":"pone.0252206.ref004","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1001\/jama.2016.0288","article-title":"Assessment of Clinical Criteria for Sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)","volume":"315","author":"CW Seymour","year":"2016","journal-title":"JAMA"},{"key":"pone.0252206.ref005","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1007\/s001340050816","article-title":"Epidemiological features and prognosis of severe community-acquired pneumococcal pneumonia","volume":"25","author":"H Georges","year":"1999","journal-title":"Intensive Care Med"},{"key":"pone.0252206.ref006","first-page":"181","article-title":"Prognostic significance of the neutrophil count in immunocompetent patients with bacteraemia","volume":"88","author":"L Leibovici","year":"1995","journal-title":"Qjm"},{"key":"pone.0252206.ref007","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1378\/chest.101.6.1656","article-title":"Evaluation of definitions for sepsis","volume":"101","author":"WA Knaus","year":"1992","journal-title":"Chest"},{"key":"pone.0252206.ref008","first-page":"1","article-title":"MIMIC-III, a freely accessible critical care database","volume":"3","author":"AEW Johnson","year":"2016","journal-title":"Sci Data"},{"key":"pone.0252206.ref009","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1093\/jamia\/ocx084","article-title":"The MIMIC Code Repository: Enabling reproducibility in critical care research","volume":"25","author":"AEW Johnson","year":"2018","journal-title":"J Am Med Informatics Assoc"},{"key":"pone.0252206.ref010","article-title":"PhysioBank, PhysioToolkit, and","volume":"101","author":"AL Goldberger","year":"2000","journal-title":"PhysioNet. 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