{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T20:16:54Z","timestamp":1788466614321,"version":"build-2803163510"},"reference-count":28,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2021,9,2]],"date-time":"2021-09-02T00:00:00Z","timestamp":1630540800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Aase og Ejnar Danielsen","award":["18-10-0370"],"award-info":[{"award-number":["18-10-0370"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Background: Septic shock patients are prone to altered fibrinolysis, which contributes to microthrombus formation, organ failure and mortality. However, characterisation of the individual patient\u2019s fibrinolytic capacity remains a challenge due to a lack of global fibrinolysis biomarkers. We aimed to assess fibrinolysis in septic shock patients using a plasma-based fibrin clot formation and lysis (clot\u2013lysis) assay and investigate the association between clot\u2013lysis parameters and other haemostatic markers, organ dysfunction and mortality. Methods: This was a prospective cohort study including adult septic shock patients (n = 34). Clot\u2013lysis was assessed using our plasma-based in-house assay. Platelet count, activated partial thromboplastin time (aPTT), international normalised ratio (INR), fibrinogen, fibrin D-dimer, antithrombin, thrombin generation, circulating fibrinolysis markers and organ dysfunction markers were analysed. Disseminated intravascular coagulation score, Sequential Organ Failure Assessment (SOFA) score and 30-day mortality were registered. Results: Three distinct clot\u2013lysis profiles emerged in the patients: (1) severely decreased fibrin formation (flat clot\u2013lysis curve), (2) normal fibrin formation and lysis and (3) pronounced lysis resistance. Patients with abnormal curves had lower platelet counts (p = 0.05), more prolonged aPTT (p = 0.04), higher lactate (p &lt; 0.01) and a tendency towards higher SOFA scores (p = 0.09) than patients with normal clot\u2013lysis curves. Fibrinogen and fibrin D-dimer were not associated with clot\u2013lysis profile (p \u2265 0.37). Conclusion: Septic shock patients showed distinct and abnormal clot\u2013lysis profiles that were associated with markers of coagulation and organ dysfunction. Our results provide important new insights into sepsis-related fibrinolysis disturbances and support the importance of assessing fibrinolytic capacity in septic shock.<\/jats:p>","DOI":"10.3390\/ijms22179540","type":"journal-article","created":{"date-parts":[[2021,9,2]],"date-time":"2021-09-02T10:02:11Z","timestamp":1630576931000},"page":"9540","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Fibrin Network Formation and Lysis in Septic Shock Patients"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2978-5185","authenticated-orcid":false,"given":"Julie Brogaard","family":"Larsen","sequence":"first","affiliation":[{"name":"Thrombosis and Haemostasis Research Unit, Department of Clinical Biochemistry, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, DK-8200 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathies Appel","family":"Aggerbeck","sequence":"additional","affiliation":[{"name":"Thrombosis and Haemostasis Research Unit, Department of Clinical Biochemistry, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, DK-8200 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim Michael","family":"Larsen","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology and Intensive Care, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, DK-8200 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine Lodberg","family":"Hvas","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology and Intensive Care, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, DK-8200 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7136-7534","authenticated-orcid":false,"given":"Anne-Mette","family":"Hvas","sequence":"additional","affiliation":[{"name":"Thrombosis and Haemostasis Research Unit, Department of Clinical Biochemistry, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, DK-8200 Aarhus, Denmark"},{"name":"Department of Clinical Medicine, Aarhus University, Palle Juul-Jensens Boulevard 82, DK-8200 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1924","DOI":"10.1111\/j.1538-7836.2004.00955.x","article-title":"Treatment effects of drotrecogin alfa (activated) in patients with severe sepsis with or without overt disseminated intravascular coagulation","volume":"2","author":"Dhainaut","year":"2004","journal-title":"J. Thromb. Haemost."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"R111","DOI":"10.1186\/cc12783","article-title":"A multicenter, prospective validation study of the Japanese Association for Acute Medicine disseminated intravascular coagulation scoring system in patients with severe sepsis","volume":"17","author":"Gando","year":"2013","journal-title":"Crit. Care"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1055\/s-0033-1334140","article-title":"Role of Fibrinolysis in Sepsis","volume":"39","author":"Gando","year":"2013","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/2052-0492-2-20","article-title":"Classifying types of disseminated intravascular coagulation: Clinical and animal models","volume":"2","author":"Asakura","year":"2014","journal-title":"J. Intensive Care"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1055\/s-0041-1725096","article-title":"Fibrinolytic Alterations in Sepsis: Biomarkers and Future Treatment Targets","volume":"47","author":"Larsen","year":"2021","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1990","DOI":"10.1007\/s00134-016-4496-z","article-title":"The effect of sepsis and its inflammatory response on mechanical clot characteristics: A prospective observational study","volume":"42","author":"Davies","year":"2016","journal-title":"Intensiv. Care Med."},{"key":"ref_7","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":"Panigada","year":"2015","journal-title":"PLoS ONE"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"224","DOI":"10.4097\/kja.19396","article-title":"Whole-blood hypocoagulable profile correlates with a greater risk of death within 28 days in patients with severe sepsis","volume":"73","author":"Boscolo","year":"2020","journal-title":"Korean J. Anesthesiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1097\/01.CCM.0000153520.31562.48","article-title":"Dynamic evolution of coagulopathy in the first day of severe sepsis: Relationship with mortality and organ failure","volume":"33","author":"Dhainaut","year":"2005","journal-title":"Crit. Care Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1111\/ijlh.12688","article-title":"Global assays of fibrinolysis","volume":"39","author":"Ilich","year":"2017","journal-title":"Int. J. Lab. Hematol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Larsen, J.B., and Hvas, A.-M. (2020). Fibrin Clot Formation and Lysis in Plasma. Methods Protoc., 3.","DOI":"10.3390\/mps3040067"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1111\/jth.14002","article-title":"An international study on the feasibility of a standardized combined plasma clot turbidity and lysis assay: Communication from the SSC of the ISTH","volume":"16","author":"Pieters","year":"2018","journal-title":"J. Thromb. Haemost."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1055\/s-0039-1685140","article-title":"Reduced Mannose-Binding Lectin-Associated Serine Protease (MASP)-1 is Associated with Disturbed Coagulation in Septic Shock","volume":"119","author":"Larsen","year":"2019","journal-title":"Thromb. Haemost."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.thromres.2018.04.025","article-title":"Fibrin clot lysis assay: Establishment of a reference interval","volume":"167","author":"Mogensen","year":"2018","journal-title":"Thromb. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e221","DOI":"10.1097\/CCM.0000000000002919","article-title":"Platelet Drop and Fibrinolytic Shutdown in Patients with Sepsis","volume":"46","author":"Semeraro","year":"2018","journal-title":"Crit. Care Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1111\/jth.12155","article-title":"Guidance for diagnosis and treatment of DIC from harmonization of the recommendations from three guidelines","volume":"11","author":"Wada","year":"2013","journal-title":"J. Thromb. Haemost."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1111\/bjh.15821","article-title":"How we manage haemostasis during sepsis","volume":"185","author":"Scully","year":"2019","journal-title":"Br. J. Haematol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1111\/j.1538-7836.2008.03063.x","article-title":"Effect of tiplaxtinin (PAI-039), an orally bioavailable PAI-1 antagonist in a rat model of thrombosis","volume":"6","author":"Hennan","year":"2008","journal-title":"J. Thromb. Haemost."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"110528","DOI":"10.1016\/j.biopha.2020.110528","article-title":"Embelin ameliorated sepsis-induced disseminated intravascular coagulation intensities by simultaneously suppressing inflammation and thrombosis","volume":"130","author":"Wang","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1002\/hep.30915","article-title":"Mixed Fibrinolytic Phenotypes in Decompensated Cirrhosis and Acute-on-Chronic Liver Failure with Hypofibrinolysis in Those with Complications and Poor Survival","volume":"71","author":"Blasi","year":"2019","journal-title":"Hepatology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1111\/jth.15112","article-title":"Global hemostatic status in patients with acute-on-chronic liver failure and septics without underlying liver disease","volume":"19","author":"Lisman","year":"2021","journal-title":"J. Thromb. Haemost."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1161\/ATVBAHA.120.315338","article-title":"COVID-19 and Sepsis Are Associated with Different Abnormalities in Plasma Procoagulant and Fibrinolytic Activity","volume":"41","author":"Bouck","year":"2020","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","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":"Schmitt","year":"2019","journal-title":"Ann. Intensiv. Care"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12959-016-0076-2","article-title":"Validation of a modified thromboelastometry approach to detect changes in fibrinolytic activity","volume":"14","author":"Kuiper","year":"2016","journal-title":"Thromb. J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2408","DOI":"10.1111\/j.1538-7836.2007.02755.x","article-title":"Tranexamic acid combined with recombinant factor VIII increases clot resistance to accelerated fibrinolysis in severe hemophilia A","volume":"5","author":"Hvas","year":"2007","journal-title":"J. Thromb. Haemost."},{"key":"ref_26","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":"Singer","year":"2016","journal-title":"JAMA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1007\/BF01709751","article-title":"The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction\/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine","volume":"22","author":"Vincent","year":"1996","journal-title":"Intensive Care Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1055\/s-0037-1616068","article-title":"Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation","volume":"86","author":"Taylor","year":"2001","journal-title":"Thromb. Haemost."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/17\/9540\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:55:01Z","timestamp":1760165701000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/17\/9540"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,2]]},"references-count":28,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["ijms22179540"],"URL":"https:\/\/doi.org\/10.3390\/ijms22179540","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,2]]}}}