{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T05:23:41Z","timestamp":1770960221774,"version":"3.50.1"},"reference-count":41,"publisher":"Georg Thieme Verlag KG","license":[{"start":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T00:00:00Z","timestamp":1745798400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The General Program of the Hunan Provincial Natural Science Foundation of China","award":["2025JJ50671"],"award-info":[{"award-number":["2025JJ50671"]}]},{"name":"The Scientific Research Plan Project of the Health Commission of Hunan Province","award":["202203023609"],"award-info":[{"award-number":["202203023609"]}]},{"name":"The Scientific Research Plan Project of the Health Commission of Hunan Province","award":["202214015252"],"award-info":[{"award-number":["202214015252"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Patients with spontaneous intracerebral hemorrhage (ICH) are at high risk of venous thromboembolism (VTE). Recent studies have shown the involvement of neutrophil extracellular traps (NETs) in thrombogenesis.<\/jats:p><jats:p>To explore the predictive value of serum MPO-DNA (a NETs surrogate) for VTE and the effect of statins on serum MPO-DNA levels and the VTE incidence in ICH patients.<\/jats:p><jats:p>This prospective cohort study enrolled 117 ICH patients and 15 healthy controls. Serum MPO-DNA levels were measured via ELISA. The relationship between serum MPO-DNA levels and VTE risk was analyzed. The predictive value of MPO-DNA was evaluated by ROC curves. Effects of statin on NETs and VTE incidence were evaluated.<\/jats:p><jats:p>The median MPO-DNA level in patients with VTE was 0.304 (95% CI: 0.231\u20130.349), significantly higher than the 0.188 (95% CI: 0.159\u20130.236) in non-VTE patients. Elevated MPO-DNA levels were associated with an increased VTE risk (OR 7.13, 95% CI 2.58\u201319.75; P\u2009&lt;\u20090.001), and this association persisted after adjustment. The AUC values for MPO-DNA, CRP, and D-dimer were 0.824 (95% CI: 0.719\u20130.928), 0.618 (95% CI: 0.481\u20130.754), and 0.786 (95% CI: 0.683\u20130.888), respectively. Moreover, statin users exhibited reduced MPO-DNA levels (0.174 vs. 0.218; P\u2009=\u20090.007), though VTE incidence differences (13.8% vs. 19.3%) lacked statistical significance.<\/jats:p><jats:p>Serum MPO-DNA serves as a sensitive biomarker for VTE prediction in ICH, highlighting NETs as potential therapeutic targets. Statins could attenuate NETosis, but larger trials are required to validate their clinical efficacy and safety in VTE prevention for ICH patients.<\/jats:p>","DOI":"10.1055\/a-2595-1927","type":"journal-article","created":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T22:48:16Z","timestamp":1745880496000},"source":"Crossref","is-referenced-by-count":2,"title":["Serum MPO-DNA for Predicting the Risk of Venous Thromboembolism and the Effect of Statins in Patients with Spontaneous Intracerebral Hemorrhage"],"prefix":"10.1055","author":[{"given":"Xinyan","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hunan Provincial People's Hospital and The First-Affiliated Hospital of Hunan Normal University, Changsha, Hunan, People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenyan","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Hunan Provincial People's Hospital and The First-Affiliated Hospital of Hunan Normal University, Changsha, Hunan, People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4460-4802","authenticated-orcid":false,"given":"Yunrong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Hunan Provincial People's Hospital and The First-Affiliated Hospital of Hunan Normal University, Changsha, Hunan, People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2025,5,9]]},"reference":[{"issue":"02","key":"ref1","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S1474-4422(09)70340-0","article-title":"Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: a systematic review and meta-analysis","volume":"9","author":"C J van Asch","year":"2010","journal-title":"Lancet Neurol"},{"issue":"15","key":"ref2","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1212\/WNL.0000000000002015","article-title":"Time trends in incidence, case fatality, and mortality of intracerebral hemorrhage","volume":"85","author":"W M Jolink","year":"2015","journal-title":"Neurology"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1016\/S0140-6736(18)31878-6","article-title":"Intracerebral haemorrhage: current approaches to acute management","volume":"392","author":"C Cordonnier","year":"2018","journal-title":"Lancet"},{"issue":"07","key":"ref4","doi-asserted-by":"crossref","first-page":"e282","DOI":"10.1161\/STR.0000000000000407","article-title":"2022 guideline for the management of patients with spontaneous intracerebral hemorrhage: a guideline from the American Heart Association\/American Stroke Association","volume":"53","author":"S M Greenberg","year":"2022","journal-title":"Stroke"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2174\/1874205X01408010001","article-title":"Risk factors for DVT\/PE in patients with stroke and intracranial hemorrhage","volume":"8","author":"M Stecker","year":"2014","journal-title":"Open Neurol J"},{"issue":"01","key":"ref6","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.jvn.2018.10.006","article-title":"Higher risk of deep vein thrombosis after hemorrhagic stroke than after acute ischemic stroke","volume":"37","author":"R Ji","year":"2019","journal-title":"J Vasc Nurs"},{"issue":"01","key":"ref7","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/s12959-021-00345-z","article-title":"Patients with venous thromboembolism after spontaneous intracerebral hemorrhage: a review","volume":"19","author":"Q Cai","year":"2021","journal-title":"Thromb J"},{"issue":"06","key":"ref8","doi-asserted-by":"crossref","first-page":"E304","DOI":"10.1093\/neuros\/nyy333","article-title":"Venous thromboembolism in patients with spontaneous intracerebral hemorrhage: a multicenter study","volume":"84","author":"D Ding","year":"2019","journal-title":"Neurosurgery"},{"issue":"05","key":"ref9","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1111\/j.1538-7836.2011.04241.x","article-title":"Efficacy and safety of anticoagulants in the prevention of venous thromboembolism in patients with acute cerebral hemorrhage: a meta-analysis of controlled studies","volume":"9","author":"M Paciaroni","year":"2011","journal-title":"J Thromb Haemost"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"1198952","DOI":"10.3389\/fimmu.2023.1198952","article-title":"Neutrophil extracellular traps mediate deep vein thrombosis: from mechanism to therapy","volume":"14","author":"M Yao","year":"2023","journal-title":"Front Immunol"},{"issue":"10","key":"ref11","doi-asserted-by":"crossref","first-page":"2544","DOI":"10.1038\/s41375-019-0500-2","article-title":"High circulating levels of MPO-DNA are associated with thrombosis in patients with MPN","volume":"33","author":"A Guy","year":"2019","journal-title":"Leukemia"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.rinim.2014.03.001","article-title":"Evidence for simvastatin anti-inflammatory actions based on quantitative analyses of NETosis and other inflammation\/oxidation markers","volume":"4","author":"W M Al-Ghoul","year":"2014","journal-title":"Results Immunol"},{"key":"ref13","first-page":"1493684","article-title":"Simvastatin reduces NETosis to attenuate severe asthma by inhibiting PAD4 expression","volume":"2023","author":"Y R Chen","year":"2023","journal-title":"Oxid Med Cell Longev"},{"issue":"10","key":"ref14","first-page":"16852","article-title":"High-dose atorvastatin and rosuvastatin reduce the levels of neutrophil extracellular trap-related proteins in coronary artery disease: association with prothrombotic state","volume":"134","author":"K St\u0119pie\u0144","year":"2024","journal-title":"Pol Arch Intern Med"},{"issue":"7814","key":"ref15","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/s41586-020-2394-6","article-title":"DNA of neutrophil extracellular traps promotes cancer metastasis via CCDC25","volume":"583","author":"L Yang","year":"2020","journal-title":"Nature"},{"issue":"06","key":"ref16","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1212\/01.wnl.0000176073.80532.a2","article-title":"Prevention of venous thrombosis in patients with acute intracerebral hemorrhage","volume":"65","author":"K Lacut","year":"2005","journal-title":"Neurology"},{"issue":"06","key":"ref17","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1159\/000511574","article-title":"PREvention of VENous Thromboembolism in Hemorrhagic Stroke Patients - PREVENTIHS Study: a randomized controlled trial and a systematic review and meta-analysis","volume":"83","author":"M Paciaroni","year":"2020","journal-title":"Eur Neurol"},{"issue":"04","key":"ref18","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.jvsv.2012.12.002","article-title":"Plasma DNA is elevated in patients with deep vein thrombosis","volume":"1","author":"J A Diaz","year":"2013","journal-title":"J Vasc Surg Venous Lymphat Disord"},{"issue":"11","key":"ref19","doi-asserted-by":"crossref","first-page":"3166","DOI":"10.1016\/j.jtha.2023.07.007","article-title":"Neutrophil extracellular trap formation is an independent risk factor for occult cancer in patients presenting with venous thromboembolism","volume":"21","author":"A Rosell","year":"2023","journal-title":"J Thromb Haemost"},{"issue":"09","key":"ref20","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1111\/j.1553-2712.2008.00203.x","article-title":"Direct comparison of the diagnostic accuracy of fifty protein biological markers of pulmonary embolism for use in the emergency department","volume":"15","author":"K E Nordenholz","year":"2008","journal-title":"Acad Emerg Med"},{"issue":"07","key":"ref21","doi-asserted-by":"crossref","first-page":"e0270865","DOI":"10.1371\/journal.pone.0270865","article-title":"Markers of neutrophil activation and neutrophil extracellular traps in diagnosing patients with acute venous thromboembolism: a feasibility study based on two VTE cohorts","volume":"17","author":"P Smith","year":"2022","journal-title":"PLoS One"},{"issue":"01","key":"ref22","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/s12959-023-00512-4","article-title":"The effect of neutrophil extracellular traps in venous thrombosis","volume":"21","author":"W Li","year":"2023","journal-title":"Thromb J"},{"issue":"21","key":"ref23","doi-asserted-by":"crossref","first-page":"8674","DOI":"10.1073\/pnas.1301059110","article-title":"Neutrophil histone modification by peptidylarginine deiminase 4 is critical for deep vein thrombosis in mice","volume":"110","author":"K Martinod","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"01","key":"ref24","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1038\/s41467-019-09160-7","article-title":"Neutrophil activation and NETosis are the major drivers of thrombosis in heparin-induced thrombocytopenia","volume":"10","author":"J Perdomo","year":"2019","journal-title":"Nat Commun"},{"issue":"01","key":"ref25","doi-asserted-by":"crossref","first-page":"218","DOI":"10.3324\/haematol.2019.217083","article-title":"Neutrophils and neutrophil extracellular traps enhance venous thrombosis in mice bearing human pancreatic tumors","volume":"105","author":"Y Hisada","year":"2020","journal-title":"Haematologica"},{"issue":"01","key":"ref26","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1111\/j.1538-7836.2011.04544.x","article-title":"Neutrophil extracellular traps promote deep vein thrombosis in mice","volume":"10","author":"A Brill","year":"2012","journal-title":"J Thromb Haemost"},{"issue":"04","key":"ref27","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1084\/jem.20112322","article-title":"Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo","volume":"209","author":"M L von Br\u00fchl","year":"2012","journal-title":"J Exp Med"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.thromres.2021.04.028","article-title":"Recombinant human DNase I for the treatment of cancer-associated thrombosis: a pre-clinical study","volume":"203","author":"C BS V\u00e1rady","year":"2021","journal-title":"Thromb Res"},{"issue":"18","key":"ref29","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1056\/NEJMoa0900241","article-title":"A randomized trial of rosuvastatin in the prevention of venous thromboembolism","volume":"360","author":"R J Glynn","year":"2009","journal-title":"N Engl J Med"},{"issue":"02","key":"ref30","doi-asserted-by":"crossref","first-page":"e83","DOI":"10.1016\/S2352-3026(16)30184-3","article-title":"Statins and primary prevention of venous thromboembolism: a systematic review and meta-analysis","volume":"4","author":"S K Kunutsor","year":"2017","journal-title":"Lancet Haematol"},{"issue":"20","key":"ref31","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1093\/eurheartj\/ehx107","article-title":"Statins and secondary prevention of venous thromboembolism: pooled analysis of published observational cohort studies","volume":"38","author":"S K Kunutsor","year":"2017","journal-title":"Eur Heart J"},{"issue":"12","key":"ref32","doi-asserted-by":"crossref","first-page":"e2348213","DOI":"10.1001\/jamanetworkopen.2023.48213","article-title":"Statin use and the risk of venous thromboembolism in women taking hormone therapy","volume":"6","author":"J W Davis","year":"2023","journal-title":"JAMA Netw 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Sci"},{"issue":"08","key":"ref36","doi-asserted-by":"crossref","first-page":"2149","DOI":"10.1161\/STROKEAHA.112.655894","article-title":"Statin therapy and the risk of intracerebral hemorrhage: a meta-analysis of 31 randomized controlled trials","volume":"43","author":"J S McKinney","year":"2012","journal-title":"Stroke"},{"issue":"01","key":"ref37","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1136\/jnnp-2024-333396","article-title":"Statin use and long-term risk of recurrent intracerebral haemorrhage: the MUCH-Italy","volume":"96","author":"A Pezzini","year":"2024","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"18","key":"ref38","doi-asserted-by":"crossref","first-page":"e1793","DOI":"10.1212\/WNL.0000000000207792","article-title":"Association of statin use with risk of stroke recurrence after intracerebral hemorrhage","volume":"101","author":"D Gaist","year":"2023","journal-title":"Neurology"},{"issue":"11","key":"ref39","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1001\/jamaneurol.2014.2124","article-title":"Effect of statin use during hospitalization for intracerebral hemorrhage on mortality and discharge disposition","volume":"71","author":"A C Flint","year":"2014","journal-title":"JAMA Neurol"},{"issue":"09","key":"ref40","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1212\/01.wnl.0000269789.09277.47","article-title":"Statin treatment withdrawal in ischemic stroke: a controlled randomized study","volume":"69","author":"M Blanco","year":"2007","journal-title":"Neurology"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"911347","DOI":"10.3389\/fimmu.2022.911347","article-title":"NETosis in psoriatic arthritis: serum MPO-DNA complex level correlates with its disease activity","volume":"13","author":"B Li","year":"2022","journal-title":"Front Immunol"}],"container-title":["Thrombosis and 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