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Stroke Res."],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The aim of this study is to investigate the association of neutrophil extracellular traps (NETs) markers with clinical and radiological outcomes in acute ischemic stroke (AIS) patients undergoing endovascular thrombectomy (EVT) and assess the effect of periprocedural heparin during EVT on NETs markers and their association with outcomes. From 198 AIS patients included in the MRCLEAN-MED trial, randomized to receive EVT with (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u2009104) or without (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u200994) low-dose unfractionated heparin (5000\u00a0IU bolus followed by 500\u00a0IU\/h for 6\u00a0h,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009104), blood samples were collected at baseline, 1\u00a0h, and 24\u00a0h post-reperfusion. NETs markers (MPO-DNA, histone-DNA, citrullinated histone H3 [CitH3]) were measured in blood samples, and their associations with stroke severity (National Institutes of Health Stroke Scale [NIHSS] score at 24\u00a0h post-reperfusion), long-term functional outcome (modified Rankin Scale [mRS] score at 90-day), and final infarct size (5\u20137\u00a0days) were assessed in EVT and heparin\u2009+\u2009EVT\u2013treated patients using logistic regression, linear regression, and Pearson\u2019s correlation. Histone-DNA levels at 1\u00a0h post-heparin\u2009+\u2009EVT, but not EVT alone, were positively associated with final infarct size. Histone-DNA levels at 24\u00a0h post-heparin\u2009+\u2009EVT were negatively associated with infarct size mRS and NIHSS, while baseline CitH3 was positively correlated with NIHSS at 24\u00a0h post-EVT. Interaction analysis showed that the association between histone-DNA levels at 24\u00a0h and NIHSS at 24\u00a0h was different in the two treatment groups. No further associations were observed. At 1\u00a0h post-heparin\u2009+\u2009EVT, the histone-DNA levels were independently associated with larger infarct size, while at 24 h, histone-DNA linked to improved outcomes post-heparin\u2009+\u2009EVT and baseline-CitH3 to worse outcomes post-EVT, suggesting heparin may attenuate histone-DNA\u2019s effect on outcome.\n                  <\/jats:p>","DOI":"10.1007\/s12975-025-01362-0","type":"journal-article","created":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T14:46:25Z","timestamp":1750949185000},"page":"1985-1995","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Association of NETs Markers with Clinical and Radiological Outcomes in Patients with Acute Ischemic Stroke Undergoing Thrombectomy: Does Heparin Treatment Modify This?"],"prefix":"10.1007","volume":"16","author":[{"given":"Aarazo","family":"Barakzie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wouter","family":"van der Steen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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Stroke. 2018;49(3):754\u20137.","journal-title":"Stroke"}],"container-title":["Translational Stroke Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12975-025-01362-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12975-025-01362-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12975-025-01362-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,8]],"date-time":"2025-11-08T20:03:24Z","timestamp":1762632204000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12975-025-01362-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,26]]},"references-count":39,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["1362"],"URL":"https:\/\/doi.org\/10.1007\/s12975-025-01362-0","relation":{},"ISSN":["1868-4483","1868-601X"],"issn-type":[{"value":"1868-4483","type":"print"},{"value":"1868-601X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,26]]},"assertion":[{"value":"7 March 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 May 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 May 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 June 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Recommended Competing Interests Statement: The authors declare the following competing interests. This study was funded by the Collaboration for New Treatments of Acute Stroke (CONTRAST) consortium, supported by the Netherlands Cardiovascular Research Initiative, an initiative of the Dutch Heart Foundation (CVON2015-01: CONTRAST); the Brain Foundation Netherlands (HA2015.01.06); and the Ministry of Economic Affairs through the PPP Allowance (LSHM17016). The study also received unrestricted funding from Stryker, Medtronic, and Cerenovus. Regarding individual disclosures, AJGJ reports speaker\u2019s fees and travel cost payments from 3SBio, Amgen, and Novartis, international advisory board membership for Novartis, and research funding from CSL Behring, Principia, SOBI, and Argenx, all unrelated to this study. HtC reports consultancy fees from Galapagos, Novostia, Alveron, AstraZeneca, and research support from Bayer. HtC is a shareholder in Coagulation Profile, a UM spinoff company, with all revenues allocated to CARIM for research purposes. D.W.J.D. and A.v.d.L. report grants from the Dutch Heart Foundation, Brain Foundation Netherlands, The Netherlands Organisation for Health Research and Development, and unrestricted grants from Cerenovus, Medtronic USA Inc, Penumbra Inc, Stryker European Operations BV, and Thrombolytic Science, LLC. C.B.L.M.M. reports a grant from the Dutch Heart Foundation and an unrestricted grant from Stryker Corporation. All other authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}]}}