{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T12:10:55Z","timestamp":1793448655718,"version":"4.5.0"},"reference-count":67,"publisher":"Georg Thieme Verlag KG","issue":"07","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Semin Thromb Hemost"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Sepsis disrupts the physiological balance between coagulation and fibrinolysis, resulting in a state in which fibrin formation exceeds fibrin removal and drives microvascular thrombosis, organ failure, and mortality. Although an early burst of endothelial tissue-type plasminogen activator (t-PA) may transiently increase plasmin generation, this phase is rapidly eclipsed by sustained upregulation of plasminogen activator inhibitor-1 (PAI-1), dysregulated activation of thrombin-activatable fibrinolysis inhibitor, depletion of endogenous anticoagulants, and progressive endotheliopathy. Beyond inhibitor excess, emerging evidence indicates that a quantitative defect in plasminogen is a central contributor to fibrinolytic insufficiency. Neutrophil extracellular traps (NETs) contain elastase, which cleaves plasminogen into inactive fragments, reducing functional plasminogen availability and impairing fibrin-bound plasmin generation. When functional plasminogen falls below rate-limiting levels, fibrin surfaces cannot efficiently support plasmin formation, resulting in persistent microvascular fibrin deposition despite elevated D-dimer concentrations. This NET\u2013plasminogen axis links immunothrombosis to the \u201cfibrinolytic insufficiency phenotype observed in sepsis-induced coagulopathy and overt disseminated intravascular coagulation (DIC).\u201d Clinically, hypofibrinolysis is characterized by high D-dimers, elevated PAI-1, reduced plasmin generation, and low fibrinolytic activity on viscoelastic testing. Multimodal assessment integrating biomarker panels and viscoelastic assays, including t-PA- or urokinase-challenged protocols, may improve risk stratification. Therapeutic strategies largely targeted coagulation; however, persistent hypofibrinolysis limits their effectiveness. Translational data demonstrate that plasminogen supplementation restores functional plasminogen levels and normalizes plasmin generation in septic patients and in experimental DIC, providing proof of concept for fibrinolysis-directed therapy. Future progress requires standardized definitions, functional fibrinolytic phenotyping, and phenotype-guided clinical trials to restore the coagulo-fibrinolytic balance in sepsis.<\/jats:p>","DOI":"10.1055\/a-2840-5585","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T23:01:06Z","timestamp":1775775666000},"page":"858-868","source":"Crossref","is-referenced-by-count":4,"title":["Redefining Fibrinolytic Insufficiency in Sepsis-Associated DIC"],"prefix":"10.1055","volume":"52","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"},{"name":"Faculty of Medical Science, Juntendo University, Urayasu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Helms","sequence":"additional","affiliation":[{"name":"Medical Intensive Care Unit, NHC, INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), Strasbourg University (UNISTRA), Strasbourg University Hospital, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl L.","family":"Maier","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Roberts","sequence":"additional","affiliation":[{"name":"Clinical Trials Unit-Global Health Clinical Trials Group, London School of Hygiene and Tropical Medicine, London, United 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Care"},{"issue":"12","key":"ref4","doi-asserted-by":"crossref","first-page":"3114","DOI":"10.1182\/blood.V78.12.3114.3114","article-title":"Basic and clinical aspects of fibrinolysis and thrombolysis","volume":"78","author":"D Collen","year":"1991","journal-title":"Blood"},{"issue":"03","key":"ref5","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1111\/j.1365-2141.2005.05444.x","article-title":"Molecular mechanisms of fibrinolysis","volume":"129","author":"G Cesarman-Maus","year":"2005","journal-title":"Br J Haematol"},{"issue":"01","key":"ref6","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1111\/j.1538-7836.2008.03220.x","article-title":"New insights into the molecular mechanisms of the fibrinolytic system","volume":"7","author":"D C Rijken","year":"2009","journal-title":"J Thromb Haemost"},{"issue":"01","key":"ref7","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1186\/s12964-024-01910-5","article-title":"A signaling pathway map of plasminogen activator inhibitor-1 (PAI-1\/SERPINE-1): a review of an innovative frontier in molecular aging and cellular senescence","volume":"22","author":"S B Shaikh","year":"2024","journal-title":"Cell Commun Signal"},{"issue":"04","key":"ref8","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1016\/j.molcel.2008.05.031","article-title":"Structure of activated thrombin-activatable fibrinolysis inhibitor, a molecular link between coagulation and fibrinolysis","volume":"31","author":"L Sanglas","year":"2008","journal-title":"Mol Cell"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"622473","DOI":"10.3389\/fcvm.2020.622473","article-title":"Targeting PAI-1 in cardiovascular disease: structural insights into PAI-1 functionality and inhibition","volume":"7","author":"M Sillen","year":"2020","journal-title":"Front Cardiovasc Med"},{"issue":"07","key":"ref10","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1046\/j.1538-7836.2003.00329.x","article-title":"Thrombin-activatable fibrinolysis inhibitor (TAFI, plasma procarboxypeptidase B, procarboxypeptidase R, procarboxypeptidase U)","volume":"1","author":"B N Bouma","year":"2003","journal-title":"J Thromb Haemost"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s40560-015-0075-6","article-title":"Recent advances in disseminated intravascular coagulation: endothelial cells and fibrinolysis in sepsis-induced DIC","volume":"3","author":"S Madoiwa","year":"2015","journal-title":"J Intensive Care"},{"issue":"11","key":"ref12","doi-asserted-by":"crossref","first-page":"2445","DOI":"10.1161\/01.ATV.0000244680.14653.9a","article-title":"Regulation of fibrinolysis by thrombin activatable fibrinolysis inhibitor, an unstable carboxypeptidase B that unites the pathways of coagulation and fibrinolysis","volume":"26","author":"L O Mosnier","year":"2006","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"12","key":"ref13","doi-asserted-by":"crossref","first-page":"3304","DOI":"10.1016\/j.jtha.2023.09.012","article-title":"The fibrinolysis renaissance","volume":"21","author":"N J Mutch","year":"2023","journal-title":"J Thromb Haemost"},{"issue":"16","key":"ref14","doi-asserted-by":"crossref","first-page":"2568","DOI":"10.1182\/blood-2014-09-599480","article-title":"Plasminogen associates with phosphatidylserine-exposing platelets and contributes to thrombus lysis under flow","volume":"125","author":"C S Whyte","year":"2015","journal-title":"Blood"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.thromres.2019.08.003","article-title":"Networks that stop the flow: a fresh look at fibrin and neutrophil extracellular traps","volume":"182","author":"I Varj\u00fa","year":"2019","journal-title":"Thromb Res"},{"issue":"15","key":"ref16","doi-asserted-by":"crossref","first-page":"12376","DOI":"10.3390\/ijms241512376","article-title":"Plasminogen 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EC Bruno","year":"2024","journal-title":"Front Cell Dev Biol"},{"issue":"05","key":"ref20","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1532\/IJH97.05190","article-title":"Plasminogen activator inhibitor 1 promotes a poor prognosis in sepsis-induced disseminated intravascular coagulation","volume":"84","author":"S Madoiwa","year":"2006","journal-title":"Int J Hematol"},{"issue":"05","key":"ref21","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1097\/SHK.0b013e3182903f0d","article-title":"Biomarkers of endothelial cell activation in early sepsis","volume":"39","author":"S Skibsted","year":"2013","journal-title":"Shock"},{"issue":"01","key":"ref22","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s13054-017-1605-5","article-title":"Shock induced endotheliopathy (SHINE) in acute critical illness - a unifying pathophysiologic mechanism","volume":"21","author":"P I Johansson","year":"2017","journal-title":"Crit Care"},{"issue":"05","key":"ref23","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1097\/ALN.0000000000003122","article-title":"Sepsis-induced coagulopathy and disseminated intravascular coagulation","volume":"132","author":"T Iba","year":"2020","journal-title":"Anesthesiology"},{"issue":"11","key":"ref24","doi-asserted-by":"crossref","first-page":"2475","DOI":"10.1111\/jth.15852","article-title":"Intracellular communication and immunothrombosis in sepsis","volume":"20","author":"T Iba","year":"2022","journal-title":"J Thromb Haemost"},{"issue":"04","key":"ref25","first-page":"666","article-title":"The role of platelets in sepsis","volume":"112","author":"S F de Stoppelaar","year":"2014","journal-title":"Thromb Haemost"},{"issue":"5663","key":"ref27","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1126\/science.1092385","article-title":"Neutrophil extracellular traps kill bacteria","volume":"303","author":"V Brinkmann","year":"2004","journal-title":"Science"},{"issue":"05","key":"ref29","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1159\/000317194","article-title":"The harmful role of C5a on innate immunity in sepsis","volume":"2","author":"P A Ward","year":"2010","journal-title":"J Innate Immun"},{"issue":"12","key":"ref30","doi-asserted-by":"crossref","first-page":"14270","DOI":"10.1096\/fj.201901363RRR","article-title":"DNA-bound elastase of neutrophil extracellular traps degrades plasminogen, reduces plasmin formation, and decreases fibrinolysis: proof of concept in septic shock plasma","volume":"33","author":"D BD Cruz","year":"2019","journal-title":"FASEB J"},{"issue":"01","key":"ref31","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.chest.2024.04.005","article-title":"Neutrophil-mediated inflammatory plasminogen degradation, rather than high plasminogen-activator inhibitor-1, may underly failures and inefficiencies of intrapleural fibrinolysis","volume":"167","author":"C D Barrett","year":"2025","journal-title":"Chest"},{"issue":"17","key":"ref32","doi-asserted-by":"crossref","first-page":"6055","DOI":"10.3390\/jcm14176055","article-title":"The fibrinolytic system in bacterial sepsis: a comprehensive review of current assessment methods","volume":"14","author":"F Scarlatescu","year":"2025","journal-title":"J Clin Med"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"16037","DOI":"10.1038\/nrdp.2016.37","article-title":"Disseminated intravascular coagulation","volume":"2","author":"S Gando","year":"2016","journal-title":"Nat Rev Dis Primers"},{"issue":"01","key":"ref34","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s13613-019-0499-6","article-title":"Acute fibrinolysis shutdown occurs early in septic shock and is associated with increased morbidity and mortality: results of an observational pilot study","volume":"9","author":"F CF Schmitt","year":"2019","journal-title":"Ann Intensive 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Haemost"},{"issue":"08","key":"ref41","doi-asserted-by":"crossref","first-page":"e0136463","DOI":"10.1371\/journal.pone.0136463","article-title":"Assessment of fibrinolysis in sepsis patients with urokinase modified thromboelastography","volume":"10","author":"M Panigada","year":"2015","journal-title":"PLoS One"},{"issue":"11","key":"ref42","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1111\/jth.14578","article-title":"Diagnosis and management of sepsis-induced coagulopathy and disseminated intravascular coagulation","volume":"17","author":"T Iba","year":"2019","journal-title":"J Thromb Haemost"},{"issue":"01","key":"ref43","doi-asserted-by":"crossref","first-page":"e884","DOI":"10.1002\/ams2.884","article-title":"Anticoagulant therapies against sepsis-induced disseminated intravascular coagulation","volume":"10","author":"Y Umemura","year":"2023","journal-title":"Acute Med Surg"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.thromres.2018.10.007","article-title":"The anticoagulant treatment for sepsis induced disseminated intravascular coagulation; network meta-analysis","volume":"171","author":"T Yatabe","year":"2018","journal-title":"Thromb Res"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"25","DOI":"10.2147\/OAEM.S135909","article-title":"Management of disseminated intravascular coagulation: current insights on antithrombin and thrombomodulin treatments","volume":"10","author":"M Hayakawa","year":"2017","journal-title":"Open Access Emerg Med"},{"issue":"03","key":"ref46","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1111\/jth.13230","article-title":"Efficacy and safety of anticoagulant therapy in three specific populations with sepsis: a meta-analysis of randomized controlled trials","volume":"14","author":"Y Umemura","year":"2016","journal-title":"J Thromb Haemost"},{"issue":"02","key":"ref47","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/j.chest.2021.08.050","article-title":"VTE prophylaxis in critically ill adults: a systematic review and network meta-analysis","volume":"161","author":"S M Fernando","year":"2022","journal-title":"Chest"},{"issue":"14","key":"ref48","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1056\/NEJMoa1014475","article-title":"Dalteparin versus unfractionated heparin in critically ill patients","volume":"364","author":"D Cook","year":"2011","journal-title":"N Engl J Med"},{"issue":"07","key":"ref49","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1111\/jth.14872","article-title":"Fibrinolytic abnormalities in acute respiratory distress syndrome (ARDS) and versatility of thrombolytic drugs to treat COVID-19","volume":"18","author":"C S Whyte","year":"2020","journal-title":"J Thromb Haemost"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s40560-020-00491-y","article-title":"Perspective on fibrinolytic therapy in COVID-19: the potential of inhalation therapy against suppressed-fibrinolytic-type DIC","volume":"8","author":"H Asakura","year":"2020","journal-title":"J Intensive Care"},{"issue":"03","key":"ref51","doi-asserted-by":"crossref","first-page":"e0120728","DOI":"10.1371\/journal.pone.0120728","article-title":"Abrogation of plasminogen activator inhibitor-1-vitronectin interaction ameliorates acute kidney injury in murine endotoxemia","volume":"10","author":"K K Gupta","year":"2015","journal-title":"PLoS One"},{"issue":"12","key":"ref52","doi-asserted-by":"crossref","first-page":"2511","DOI":"10.1161\/01.ATV.20.12.2511","article-title":"Thrombin activatable fibrinolysis inhibitor and an antifibrinolytic pathway","volume":"20","author":"L Bajzar","year":"2000","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"09","key":"ref54","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1111\/trf.17939","article-title":"Plasma as endothelial rescue in septic shock: a randomized, phase 2a pilot trial","volume":"64","author":"N E Clausen","year":"2024","journal-title":"Transfusion"},{"issue":"08","key":"ref55","doi-asserted-by":"crossref","first-page":"e166044","DOI":"10.1172\/jci.insight.166044","article-title":"Plasmin and plasminogen prevent sepsis severity by reducing neutrophil extracellular traps and systemic inflammation","volume":"8","author":"J P Vago","year":"2023","journal-title":"JCI Insight"},{"issue":"01","key":"ref56","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s13054-018-2292-6","article-title":"The glycocalyx: a novel diagnostic and therapeutic target in sepsis","volume":"23","author":"R Uchimido","year":"2019","journal-title":"Crit Care"},{"issue":"01","key":"ref57","doi-asserted-by":"crossref","first-page":"23","DOI":"10.14789\/jmj.JMJ23-0041-P","article-title":"Endothelial glycocalyx protection in sepsis","volume":"70","author":"J H Levy","year":"2024","journal-title":"Juntendo Iji Zasshi"},{"issue":"03","key":"ref58","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1213\/ANE.0000000000004234","article-title":"Fibrinolysis shutdown in trauma: historical review and clinical implications","volume":"129","author":"H B Moore","year":"2019","journal-title":"Anesth Analg"},{"issue":"06","key":"ref59","doi-asserted-by":"crossref","first-page":"416","DOI":"10.14789\/ejmj.JMJ24-0035-P","article-title":"Fibrinolytic changes in critical illnesses: is fibrinolysis shutdown a specific concept?","volume":"70","author":"J H Levy","year":"2024","journal-title":"Juntendo Iji Zasshi"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1016\/S0140-6736(19)33157-5","article-title":"Plasma-first resuscitation to treat haemorrhagic shock in urban areas - authors' reply","volume":"395","author":"M P Chapman","year":"2020","journal-title":"Lancet"},{"issue":"01","key":"ref61","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1055\/s-0039-1694995","article-title":"Sepsis-induced coagulopathy and disseminated intravascular coagulation","volume":"46","author":"T Iba","year":"2020","journal-title":"Semin Thromb Hemost"},{"issue":"02","key":"ref62","doi-asserted-by":"crossref","first-page":"R79","DOI":"10.1186\/cc8992","article-title":"4G\/5G polymorphism of PAI-1 gene is associated with multiple organ dysfunction and septic shock in pneumonia induced severe sepsis: prospective, observational, genetic study","volume":"14","author":"K Mad\u00e1ch","year":"2010","journal-title":"Crit Care"},{"issue":"02","key":"ref63","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.jamcollsurg.2020.05.007","article-title":"Fibrinolysis shutdown correlation with thromboembolic events in severe COVID-19 infection","volume":"231","author":"F L Wright","year":"2020","journal-title":"J Am Coll Surg"},{"issue":"20","key":"ref64","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.1001\/jama.2019.5358","article-title":"Effect of a recombinant human soluble thrombomodulin on mortality in patients with sepsis-associated coagulopathy: the SCARLET randomized clinical trial","volume":"321","author":"J L Vincent","year":"2019","journal-title":"JAMA"},{"issue":"01","key":"ref65","doi-asserted-by":"crossref","first-page":"e950","DOI":"10.1002\/ams2.950","article-title":"Efficacy of antithrombin administration for patients with sepsis: a systematic review, meta-analysis, and meta-regression","volume":"11","author":"T Tsuchida","year":"2024","journal-title":"Acute Med Surg"},{"issue":"10","key":"ref66","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1182\/blood-2016-09-741298","article-title":"Platelets and neutrophil extracellular traps collaborate to promote intravascular coagulation during sepsis in mice","volume":"129","author":"B McDonald","year":"2017","journal-title":"Blood"},{"issue":"08","key":"ref67","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1038\/nm.2843","article-title":"The pulmonary endothelial glycocalyx regulates neutrophil adhesion and lung injury during experimental sepsis","volume":"18","author":"E P Schmidt","year":"2012","journal-title":"Nat Med"},{"issue":"07","key":"ref68","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1001\/jama.2020.11946","article-title":"Effect of ascorbic acid, corticosteroids, and thiamine on organ injury in septic shock: the ACTS randomized clinical trial","volume":"324","author":"A Moskowitz","year":"2020","journal-title":"JAMA"},{"issue":"06","key":"ref69","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1016\/j.amjsurg.2017.09.018","article-title":"Disparate effects of catecholamines under stress conditions on endothelial glycocalyx injury: an in 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