{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:17:44Z","timestamp":1790266664892,"version":"4.1.0"},"reference-count":37,"publisher":"Georg Thieme Verlag KG","issue":"07","funder":[{"name":"The Promotion and Mutual Aid Corporation for Private Schools of Japan"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Semin Thromb Hemost"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Historically, heparin has had the longest historical use as an anticoagulant and continues this day to be the primary therapeutic option for preventing thrombosis and thromboembolism in critically ill hospitalized patients. Heparin is also used to treat sepsis and sepsis-associated disseminated intravascular coagulation (DIC) in various countries. However, the efficacy and safety of heparin for this indication remains controversial, as adequately powered randomized clinical studies have not demonstrated as yet a survival benefit in sepsis and sepsis-associated DIC, despite meta-analyses and propensity analyses reporting improved outcomes without increasing bleeding risk. Further, activated protein C and recombinant thrombomodulin showed greater improvements in outcomes compared with heparin, although these effects were inconclusive. In summary, further research is warranted, despite the ongoing clinical use of heparin for sepsis and sepsis-associated DIC. Based on Japanese guidelines, antithrombin or recombinant thrombomodulin may be a preferable choice if they are accessible.<\/jats:p>","DOI":"10.1055\/s-0044-1786754","type":"journal-article","created":{"date-parts":[[2024,5,11]],"date-time":"2024-05-11T22:31:37Z","timestamp":1715466697000},"page":"1012-1018","source":"Crossref","is-referenced-by-count":11,"title":["Heparins May Not Be the Optimal Anticoagulants for Sepsis and Sepsis-Associated Disseminated Intravascular Coagulation"],"prefix":"10.1055","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0255-4088","authenticated-orcid":false,"given":"Toshiaki","family":"Iba","sequence":"additional","affiliation":[{"name":"Department of Emergency and Disaster Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0895-6800","authenticated-orcid":false,"given":"Julie","family":"Helms","sequence":"additional","affiliation":[{"name":"Strasbourg University Hospital, Medical Intensive Care Unit - NHC, INSERM (French National Institute of Health and Medical Research), Strasbourg University (UNISTRA), UMR 1260, Regenerative Nanomedicine (RNM), FMTS, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7188-5876","authenticated-orcid":false,"given":"Takaaki","family":"Totoki","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Kyushu University, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3766-4962","authenticated-orcid":false,"given":"Jerrold H.","family":"Levy","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Critical Care, and Surgery, Duke University School of Medicine, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2024,5,11]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.thromres.2019.04.025","article-title":"Role of disseminated intravascular coagulation in severe sepsis","volume":"178","author":"S Gando","year":"2019","journal-title":"Thromb Res"},{"issue":"01","key":"ref2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.jtha.2023.07.020","article-title":"Thromboinflammation in acute injury: infections, heatstroke, and trauma","volume":"22","author":"T Iba","year":"2024","journal-title":"J Thromb Haemost"},{"issue":"05","key":"ref3","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1111\/bjh.17172","article-title":"Disseminated intravascular coagulation: epidemiology, biomarkers, and management","volume":"192","author":"K Adelborg","year":"2021","journal-title":"Br J Haematol"},{"issue":"22","key":"ref5","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1056\/NEJM199105303242206","article-title":"Heparin","volume":"324","author":"J Hirish","year":"1991","journal-title":"N Engl J Med"},{"issue":"03","key":"ref6","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1111\/bjh.14885","article-title":"The role of heparin in sepsis: much more than just an anticoagulant","volume":"179","author":"X Li","year":"2017","journal-title":"Br J Haematol"},{"issue":"04","key":"ref7","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1097\/01.CCM.0000059441.70680.DC","article-title":"Evaluation of antiinflammatory and antiadhesive effects of heparins in human endotoxemia","volume":"31","author":"U Derhaschnig","year":"2003","journal-title":"Crit Care Med"},{"issue":"05","key":"ref8","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1164\/rccm.200612-1803OC","article-title":"Prophylactic heparin in patients with severe sepsis treated with drotrecogin alfa (activated)","volume":"176","author":"M Levi","year":"2007","journal-title":"Am J Respir Crit Care Med"},{"issue":"04","key":"ref9","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1097\/CCM.0b013e31819c06bc","article-title":"Unfractioned heparin for treatment of sepsis: a randomized clinical trial (The HETRASE Study)","volume":"37","author":"F Jaimes","year":"2009","journal-title":"Crit Care Med"},{"issue":"05","key":"ref10","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1186\/s13054-014-0563-4","article-title":"Heparin therapy reduces 28-day mortality in adult severe sepsis patients: a systematic review and meta-analysis","volume":"18","author":"C Wang","year":"2014","journal-title":"Crit Care"},{"issue":"15","key":"ref11","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1001\/jama.286.15.1869","article-title":"Caring for the critically ill patient. 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