{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T00:56:10Z","timestamp":1776473770453,"version":"3.51.2"},"reference-count":43,"publisher":"Elsevier BV","issue":"6","license":[{"start":{"date-parts":[[2024,6,1]],"date-time":"2024-06-01T00:00:00Z","timestamp":1717200000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,6,1]],"date-time":"2024-06-01T00:00:00Z","timestamp":1717200000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"vor","delay-in-days":365,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100008648","name":"Pfizer Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008648","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["1588"],"award-info":[{"award-number":["1588"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["jthjournal.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Thrombosis and Haemostasis"],"published-print":{"date-parts":[[2024,6]]},"DOI":"10.1016\/j.jtha.2024.02.005","type":"journal-article","created":{"date-parts":[[2024,2,19]],"date-time":"2024-02-19T12:09:02Z","timestamp":1708344542000},"page":"1558-1568","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":4,"title":["Endogenous thrombin potential and time-dependent thrombin generation parameters are independent risk factors for mortality in the general population"],"prefix":"10.1016","volume":"22","author":[{"given":"Romy","family":"de Laat-Kremers","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simona","family":"Costanzo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Roest","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amalia","family":"De Curtis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dana","family":"Huskens","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Augusto","family":"Di Castelnuovo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marisa","family":"Ninivaggi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Cerletti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Benedetta","family":"Donati","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bas","family":"de Laat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Licia","family":"Iacoviello","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.jtha.2024.02.005_bib1","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1038\/nature06797","article-title":"Triggers, targets and treatments for thrombosis","volume":"451","author":"Mackman","year":"2008","journal-title":"Nature"},{"key":"10.1016\/j.jtha.2024.02.005_bib2","doi-asserted-by":"crossref","first-page":"1908","DOI":"10.1111\/jth.13441","article-title":"Coagulation and non-coagulation effects of thrombin","volume":"14","author":"Posma","year":"2016","journal-title":"J\u00a0Thromb Haemost"},{"key":"10.1016\/j.jtha.2024.02.005_bib3","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1213\/ane.0b013e31819bcc9c","article-title":"Blood coagulation: hemostasis and thrombin regulation","volume":"108","author":"Tanaka","year":"2009","journal-title":"Anesth Analg"},{"key":"10.1016\/j.jtha.2024.02.005_bib4","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1152\/physrev.00016.2011","article-title":"New fundamentals in hemostasis","volume":"93","author":"Versteeg","year":"2013","journal-title":"Physiol Rev"},{"key":"10.1016\/j.jtha.2024.02.005_bib5","series-title":"GeneReviews(\u00ae)","article-title":"Factor V Leiden thrombophilia","author":"Kujovich","year":"1993"},{"key":"10.1016\/j.jtha.2024.02.005_bib6","first-page":"255","article-title":"Prevalence of positive factor V Leiden and prothrombin mutations in samples tested for thrombophilia in Saudi Arabia","volume":"11","author":"Madkhaly","year":"2021","journal-title":"Am J Blood Res"},{"key":"10.1016\/j.jtha.2024.02.005_bib7","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1007\/s11239-012-0824-5","article-title":"Homozygous factor V Leiden and double heterozygosity for factor V Leiden and prothrombin mutation","volume":"36","author":"Saemundsson","year":"2013","journal-title":"J\u00a0Thromb Thrombolysis"},{"key":"10.1016\/j.jtha.2024.02.005_bib8","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1097\/01.coc.0000436088.69084.22","article-title":"Clinical and prognostic significance of coagulation assays in pancreatic cancer patients with absence of venous thromboembolism","volume":"38","author":"Sun","year":"2015","journal-title":"Am J Clin Oncol"},{"key":"10.1016\/j.jtha.2024.02.005_bib9","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1080\/10245332.2017.1365458","article-title":"Can biomarkers of coagulation, platelet activation, and inflammation predict mortality in patients with hematological malignancies?","volume":"23","author":"Elmoamly","year":"2018","journal-title":"Hematology"},{"key":"10.1016\/j.jtha.2024.02.005_bib10","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0271663","article-title":"Moli-sani Investigators. Low antithrombin levels are associated with low risk of cardiovascular death but are a risk factor for cancer mortality","volume":"17","author":"Iacoviello","year":"2022","journal-title":"PLoS One"},{"key":"10.1016\/j.jtha.2024.02.005_bib11","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.thromres.2022.03.013","article-title":"Associations between hemostatic markers and mortality in COVID-19 - compounding effects of D-dimer, antithrombin and PAP complex","volume":"213","author":"Bokn\u00e4s","year":"2022","journal-title":"Thromb Res"},{"key":"10.1016\/j.jtha.2024.02.005_bib12","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1046\/j.1365-2796.2002.00997.x","article-title":"Is lipoprotein(a) a predictor for survival in patients with established coronary artery disease? Results from a prospective patient cohort study in northern Sweden","volume":"252","author":"Glader","year":"2002","journal-title":"J\u00a0Intern Med"},{"key":"10.1016\/j.jtha.2024.02.005_bib13","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.blre.2012.06.001","article-title":"Thrombin generation: what have we learned?","volume":"26","author":"Al Dieri","year":"2012","journal-title":"Blood Rev"},{"key":"10.1016\/j.jtha.2024.02.005_bib14","article-title":"In patients with hemophilia, a decreased thrombin generation profile is associated with a severe bleeding phenotype","volume":"7","author":"Verhagen","year":"2023","journal-title":"Res Pract Thromb Haemost"},{"key":"10.1016\/j.jtha.2024.02.005_bib15","doi-asserted-by":"crossref","DOI":"10.1016\/j.rpth.2022.100018","article-title":"Thrombin generation and implications for hemophilia therapies: a narrative review","volume":"7","author":"Sidonio","year":"2023","journal-title":"Res Pract Thromb Haemost"},{"key":"10.1016\/j.jtha.2024.02.005_bib16","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1007\/s12630-021-02165-1","article-title":"The association of thrombin generation with bleeding outcomes in cardiac surgery: a prospective observational study","volume":"69","author":"Bartoszko","year":"2022","journal-title":"Can J Anaesth"},{"key":"10.1016\/j.jtha.2024.02.005_bib17","doi-asserted-by":"crossref","first-page":"2918","DOI":"10.1111\/jth.15538","article-title":"Clinical use of thrombin generation assays","volume":"19","author":"Binder","year":"2021","journal-title":"J\u00a0Thromb Haemost"},{"key":"10.1016\/j.jtha.2024.02.005_bib18","doi-asserted-by":"crossref","DOI":"10.3389\/fcvm.2023.1075121","article-title":"Application of the thrombin generation assay in patients with antiphospholipid syndrome: a systematic review of the literature","volume":"10","author":"Gehlen","year":"2023","journal-title":"Front Cardiovasc Med"},{"key":"10.1016\/j.jtha.2024.02.005_bib19","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1111\/jth.14863","article-title":"Towards standardization of thrombin generation assays: inventory of thrombin generation methods based on results of an International Society of Thrombosis and Haemostasis Scientific Standardization Committee survey","volume":"18","author":"de Laat-Kremers","year":"2020","journal-title":"J\u00a0Thromb Haemost"},{"key":"10.1016\/j.jtha.2024.02.005_bib20","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.thromres.2018.10.005","article-title":"The anticoagulant effect of dabigatran is reflected in the lag time and time-to-peak, but not in the endogenous thrombin potential or peak, of thrombin generation","volume":"171","author":"Bloemen","year":"2018","journal-title":"Thromb Res"},{"key":"10.1016\/j.jtha.2024.02.005_bib21","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1160\/TH06-03-0179","article-title":"Use of calibrated automated thrombinography\u00a0+\/- thrombomodulin to recognise the prothrombotic phenotype","volume":"96","author":"Dargaud","year":"2006","journal-title":"Thromb Haemost"},{"key":"10.1016\/j.jtha.2024.02.005_bib22","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1161\/01.ATV.18.8.1287","article-title":"Clinical studies and thrombin generation in patients homozygous or heterozygous for the G20210A mutation in the prothrombin gene","volume":"18","author":"Kyrle","year":"1998","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"10.1016\/j.jtha.2024.02.005_bib23","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1111\/j.1365-2141.2007.06738.x","article-title":"Elevated endogenous thrombin potential is associated with an increased risk of a first deep venous thrombosis but not with the risk of recurrence","volume":"138","author":"van Hylckama Vlieg","year":"2007","journal-title":"Br J Haematol"},{"key":"10.1016\/j.jtha.2024.02.005_bib24","doi-asserted-by":"crossref","first-page":"110","DOI":"10.2427\/5886","article-title":"The Moli-sani project, a randomized, prospective cohort study in the Molise region in Italy; design, rationale and objectives","volume":"4","author":"Iacoviello","year":"2007","journal-title":"Italian J Public Health"},{"key":"10.1016\/j.jtha.2024.02.005_bib25","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/j.numecd.2008.11.009","article-title":"Dietary patterns, cardiovascular risk factors and C-reactive protein in a healthy Italian population","volume":"19","author":"Centritto","year":"2009","journal-title":"Nutr Metab Cardiovasc Dis"},{"key":"10.1016\/j.jtha.2024.02.005_bib26","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1111\/ijlh.12784","article-title":"Pre-analytical stability of coagulation parameters in plasma stored at room temperature","volume":"40","author":"Linskens","year":"2018","journal-title":"Int J Lab Hematol"},{"key":"10.1016\/j.jtha.2024.02.005_bib27","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1159\/000071636","article-title":"Calibrated automated thrombin generation measurement in clotting plasma","volume":"33","author":"Hemker","year":"2003","journal-title":"Pathophysiol Haemost Thromb"},{"key":"10.1016\/j.jtha.2024.02.005_bib28","doi-asserted-by":"crossref","DOI":"10.3389\/fcvm.2022.897733","article-title":"Increased BMI and blood lipids are associated with a hypercoagulable state in the Moli-sani cohort","volume":"9","author":"de Laat-Kremers","year":"2022","journal-title":"Front Cardiovasc Med"},{"key":"10.1016\/j.jtha.2024.02.005_bib29","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.jtha.2022.11.029","article-title":"DOAC-associated bleeding, hemostatic strategies, and thrombin generation assays - a review of the literature","volume":"21","author":"Shaw","year":"2023","journal-title":"J\u00a0Thromb Haemost"},{"key":"10.1016\/j.jtha.2024.02.005_bib30","doi-asserted-by":"crossref","first-page":"3253","DOI":"10.1177\/0271678X17695572","article-title":"Inflammatory and metalloproteinases profiles predict three-month poor outcomes in ischemic stroke treated with thrombolysis","volume":"37","author":"Gori","year":"2017","journal-title":"J\u00a0Cereb Blood Flow Metab"},{"key":"10.1016\/j.jtha.2024.02.005_bib31","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.ijid.2020.02.026","article-title":"Towards identification of novel putative biomarkers for infective endocarditis by serum proteomic analysis","volume":"96","author":"Snips\u00f8yr","year":"2020","journal-title":"Int J Infect Dis"},{"key":"10.1016\/j.jtha.2024.02.005_bib32","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0237024","article-title":"Thrombin generation's role in predicting coronary disease severity","volume":"15","author":"Elad","year":"2020","journal-title":"PLoS One"},{"key":"10.1016\/j.jtha.2024.02.005_bib33","doi-asserted-by":"crossref","first-page":"E36","DOI":"10.1111\/hepr.12520","article-title":"Thrombin generation measured as thrombin-antithrombin complexes predicts clinical outcomes in patients with cirrhosis","volume":"46","author":"Kalambokis","year":"2016","journal-title":"Hepatol Res"},{"key":"10.1016\/j.jtha.2024.02.005_bib34","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0180477","article-title":"Low thrombin generation predicts poor prognosis in ischemic stroke patients after thrombolysis","volume":"12","author":"Hudak","year":"2017","journal-title":"PLoS One"},{"key":"10.1016\/j.jtha.2024.02.005_bib35","doi-asserted-by":"crossref","first-page":"7792","DOI":"10.1038\/s41598-021-85906-y","article-title":"Prognostic value of thrombin generation parameters in hospitalized COVID-19 patients","volume":"11","author":"de la Morena-Barrio","year":"2021","journal-title":"Sci Rep"},{"key":"10.1016\/j.jtha.2024.02.005_bib36","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1160\/TH05-10-0685","article-title":"Age-dependency of thrombin generation measured by means of calibrated automated thrombography (CAT)","volume":"95","author":"Haidl","year":"2006","journal-title":"Thromb Haemost"},{"key":"10.1016\/j.jtha.2024.02.005_bib37","first-page":"378","article-title":"Thrombin generation increasing with age and decreasing with use of heparin indicated by calibrated automated thrombogram conducted in Chinese","volume":"27","author":"Wu","year":"2014","journal-title":"Biomed Environ Sci"},{"key":"10.1016\/j.jtha.2024.02.005_bib38","doi-asserted-by":"crossref","first-page":"2327","DOI":"10.3324\/haematol.2019.221655","article-title":"Thrombin generation in cardiovascular disease and mortality - results from the Gutenberg Health Study","volume":"105","author":"van Paridon","year":"2020","journal-title":"Haematologica"},{"key":"10.1016\/j.jtha.2024.02.005_bib39","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1093\/gerona\/glu228","article-title":"Associations between thrombin generation and the risk of cardiovascular disease in elderly patients: results from the PROSPER study","volume":"70","author":"Loeffen","year":"2015","journal-title":"J\u00a0Gerontol A Biol Sci Med Sci"},{"key":"10.1016\/j.jtha.2024.02.005_bib40","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1111\/j.1538-7836.2007.02824.x","article-title":"Coagulation factors and the protein C system as determinants of thrombin generation in a normal population","volume":"6","author":"Dielis","year":"2008","journal-title":"J\u00a0Thromb Haemost"},{"key":"10.1016\/j.jtha.2024.02.005_bib41","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/S0049-3848(00)00424-2","article-title":"Factor VII, tissue factor pathway inhibitor, and monocyte tissue factor in diabetes mellitus: influence of type of diabetes, obesity index, and age","volume":"101","author":"Vambergue","year":"2001","journal-title":"Thromb Res"},{"key":"10.1016\/j.jtha.2024.02.005_bib42","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1111\/j.1538-7836.2010.03743.x","article-title":"Thrombin generation-based assays to measure the activity of the TFPI-protein S pathway in plasma from normal and protein S-deficient individuals","volume":"8","author":"Maurissen","year":"2010","journal-title":"J\u00a0Thromb Haemost"},{"key":"10.1016\/j.jtha.2024.02.005_bib43","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1160\/TH07-03-0212","article-title":"VTE Impact Assessment Group in Europe (VITAE). Venous thromboembolism (VTE) in Europe. The number of VTE events and associated morbidity and mortality","volume":"98","author":"Cohen","year":"2007","journal-title":"Thromb Haemost"}],"container-title":["Journal of Thrombosis and Haemostasis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S153878362400103X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S153878362400103X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T21:09:59Z","timestamp":1762549799000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S153878362400103X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6]]},"references-count":43,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,6]]}},"alternative-id":["S153878362400103X"],"URL":"https:\/\/doi.org\/10.1016\/j.jtha.2024.02.005","relation":{},"ISSN":["1538-7836"],"issn-type":[{"value":"1538-7836","type":"print"}],"subject":[],"published":{"date-parts":[[2024,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Endogenous thrombin potential and time-dependent thrombin generation parameters are independent risk factors for mortality in the general population","name":"articletitle","label":"Article Title"},{"value":"Journal of Thrombosis and Haemostasis","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jtha.2024.02.005","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}