{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:50:31Z","timestamp":1787028631893,"version":"build-2736575974"},"reference-count":45,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,27]],"date-time":"2022-12-27T00:00:00Z","timestamp":1672099200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin"},{"name":"BIH"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Elevated serum ferritin is a common condition in critically ill patients. It is well known that hyperferritinemia constitutes a good biomarker for hemophagocytic lymphohistiocytosis (HLH) in critically ill patients. However, further differential diagnoses of hyperferritinemia in adult critically ill patients remain poorly investigated. We sought to systematically investigate hyperferritinemia in adult critically ill patients without HLH. Methods: In this secondary analysis of a retrospective observational study, patients \u226518 years admitted to at least one adult intensive care unit at Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin between January 2006 and August 2018, and with hyperferritinemia of \u2265500 \u03bcg\/L were included. Patients with HLH were excluded. All patients were categorized into non-sepsis, sepsis, and septic shock. They were also classified into 17 disease groups, based on their ICD-10 codes, and pre-existing immunosuppression was determined. Uni- and multivariable linear regression analyses were performed in all patients. Results: A total of 2583 patients were analyzed. Multivariable linear regression analysis revealed positive associations of maximum SOFA score, sepsis or septic shock, liver disease (except hepatitis), and hematological malignancy with maximum ferritin. T\/NK cell lymphoma, acute myeloblastic leukemia, Kaposi\u2019s sarcoma, acute or subacute liver failure, and hepatic veno-occlusive disease were positively associated with maximum ferritin in post-hoc multivariable linear regression analysis. Conclusions: Sepsis or septic shock, liver disease (except hepatitis) and hematological malignancy are important differential diagnoses in hyperferritinemic adult critically ill patients without HLH. Together with HLH, they complete the quartet of important differential diagnoses of hyperferritinemia in adult critically ill patients. As these conditions are also related to HLH, it is important to apply HLH-2004 criteria for exclusion of HLH in hyperferritinemic patients. Hyperferritinemic critically ill patients without HLH require quick investigation of differential diagnoses.<\/jats:p>","DOI":"10.3390\/jcm12010192","type":"journal-article","created":{"date-parts":[[2022,12,27]],"date-time":"2022-12-27T03:03:31Z","timestamp":1672110211000},"page":"192","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Differential Diagnosis of Hyperferritinemia in Critically Ill Patients"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5447-7929","authenticated-orcid":false,"given":"Friederike S.","family":"Schuster","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Nyvlt","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Heeren","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1062-0495","authenticated-orcid":false,"given":"Claudia","family":"Spies","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moritz F.","family":"Adam","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Schenk","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Universit\u00e4tsklinikum Jena, 07743 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank M.","family":"Brunkhorst","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, Center for Clinical Studies, Universit\u00e4tsklinikum Jena, 07743 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gritta","family":"Janka","sequence":"additional","affiliation":[{"name":"Clinic of Pediatric Hematology and Oncology, University Medical Center Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"La Ros\u00e9e","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Innere Medizin II, Schwarzwald-Baar-Klinikum, 78052 Villingen-Schwenningen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia","family":"Lachmann","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 13353 Berlin, Germany"},{"name":"Berlin Institute of Health (BIH) at Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, 10178 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2330-9839","authenticated-orcid":false,"given":"Gunnar","family":"Lachmann","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 13353 Berlin, Germany"},{"name":"Berlin Institute of Health (BIH) at Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, 10178 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5818","DOI":"10.1128\/MCB.20.16.5818-5827.2000","article-title":"Coordinate transcriptional and translational regulation of ferritin in response to oxidative stress","volume":"20","author":"Tsuji","year":"2000","journal-title":"Mol. 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