{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T17:11:05Z","timestamp":1790961065402,"version":"4.1.0"},"reference-count":22,"publisher":"Georg Thieme Verlag KG","issue":"07","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Semin Thromb Hemost"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The release of extracellular traps by neutrophils (NETs) represents a novel active mechanism of cell death that has been recently implicated in the pathogenesis of thrombotic disorders. The aim of this study was to investigate the generation of NETs in different groups of patients with acute thrombotic events (ATEs) and to establish whether NETs markers can predict the risk of new cardiovascular events. We performed a case\u2013control study of patients with ATE, including acute coronary syndrome (n\u2009=\u200960), cerebrovascular accident (n\u2009=\u200950), and venous thromboembolism (n\u2009=\u200955). Control subjects (n\u2009=\u200970) were identified among patients admitted for acute chest pain and in which a diagnosis of ATE was excluded. Serum levels of NET markers and neutrophil activation, such as myeloperoxidase (MPO)-DNA complexes, neutrophil gelatinase-associated lipocalin, polymorphonuclear neutrophil elastase, lactoferrin, and MPO, were measured in each patient. We found that circulating levels of MPO-DNA complexes were significantly increased in patients with ATE (p\u2009&lt;\u20090.001) compared with controls and that this association remained significant even after fully adjustment for traditional risk factors (p\u2009=\u20090.001). A receiver operating characteristics analysis of circulating MPO-DNA complexes in discriminating between controls and patients with ATE showed a significant area under the curve of 0.76 (95% confidence interval: 0.69\u20130.82). After a median follow-up of 40.7 (\u00b1\u200913.8) months, 24 out of the 165 patients with ATE presented a new cardiovascular event and 18 patients died. None of the markers under investigation influenced survival or the incidence of new cardiovascular events. In conclusion, we found that increase of markers of NETosis can be observed in acute thrombotic conditions, occurring both on the arterial and venous site. Nevertheless, the level of neutrophil markers measured during the ATE is not predictive of future risk of mortality and cardiovascular events.<\/jats:p>","DOI":"10.1055\/s-0043-1769510","type":"journal-article","created":{"date-parts":[[2023,6,12]],"date-time":"2023-06-12T23:18:45Z","timestamp":1686611925000},"page":"709-715","source":"Crossref","is-referenced-by-count":11,"title":["NETosis in Acute Thrombotic Disorders"],"prefix":"10.1055","volume":"49","author":[{"given":"Alessandro","family":"Bressan","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Padova, Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Faggin","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Padova, Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maristella","family":"Donato","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Tonon","sequence":"additional","affiliation":[{"name":"Medicine 1^, Ca' Foncello University Hospital, Treviso, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Buso","sequence":"additional","affiliation":[{"name":"Medicine 1^, Ca' Foncello University Hospital, Treviso, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Nardin","sequence":"additional","affiliation":[{"name":"Medicine 1^, Ca' Foncello University Hospital, Treviso, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Tiepolo","sequence":"additional","affiliation":[{"name":"Medicine 1^, Ca' Foncello University Hospital, Treviso, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Cinetto","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Padova, Padova, Italy"},{"name":"Medicine 1^, Ca' Foncello University Hospital, Treviso, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Scarpa","sequence":"additional","affiliation":[{"name":"Medicine 1^, Ca' Foncello University Hospital, Treviso, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Agostini","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Padova, Padova, Italy"},{"name":"Medicine 1^, Ca' Foncello University Hospital, Treviso, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Pauletto","sequence":"additional","affiliation":[{"name":"Medicine 1^, Ca' Foncello University Hospital, Treviso, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Ventura","sequence":"additional","affiliation":[{"name":"Department of Statistical Sciences, University of Padova, Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Fusaro","sequence":"additional","affiliation":[{"name":"Radiology Unit, Oderzo Hospital, Treviso, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Felice","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Padova, Padova, Italy"},{"name":"Medicine 1^, Ca' Foncello University Hospital, Treviso, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcello","family":"Rattazzi","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Padova, Padova, Italy"},{"name":"Medicine 1^, Ca' Foncello University Hospital, Treviso, 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Donkel","year":"2021","journal-title":"PLoS One"},{"issue":"08","key":"ref7","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.1161\/ATVBAHA.113.301627","article-title":"Elevated levels of circulating DNA and chromatin are independently associated with severe coronary atherosclerosis and a prothrombotic state","volume":"33","author":"J I Borissoff","year":"2013","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"21","key":"ref8","doi-asserted-by":"crossref","first-page":"2928","DOI":"10.1080\/15384101.2019.1662678","article-title":"Neutrophil extracellular traps induced by IL-8 aggravate atherosclerosis via activation NF-\u03baB signaling in macrophages","volume":"18","author":"Z An","year":"2019","journal-title":"Cell Cycle"},{"issue":"02","key":"ref9","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1111\/1756-185X.13226","article-title":"Increased levels of neutrophil extracellular trap remnants in the serum of patients with rheumatoid 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