{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T13:15:11Z","timestamp":1788959711549,"version":"build-2803163510"},"reference-count":51,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T00:00:00Z","timestamp":1777075200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T00:00:00Z","timestamp":1777075200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000288","name":"Royal Society","doi-asserted-by":"publisher","award":["WM170007"],"award-info":[{"award-number":["WM170007"]}],"id":[{"id":"10.13039\/501100000288","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2026,6]]},"abstract":"\n Abstract<\/jats:title>\n \n Psychological stress is a recognised, yet mechanistically unresolved, risk factor for cardiovascular disease (CVD) partly through its association with a hypercoagulable state. Free radical\u2013mediated oxidative stress has been proposed as a key upstream driver of this haemostatic imbalance. In this randomised cross\u2010over study we investigated whether acute psychological stress promotes systemic radical formation and prothrombotic alterations in clot microstructure in eight healthy males. The Trier Social Stress Test was used to induce psychological stress. Antecubital venous blood was collected to measure the ascorbate free radical (A\n \u2022\u2212<\/jats:sup>\n , electron paramagnetic resonance spectroscopy) and clot microstructure (D\n f<\/jats:sub>\n , Fourier transform rheology), alongside standard coagulometry. Compared with the control condition (quiet sitting), psychological stress increased A\n \u2022\u2212<\/jats:sup>\n (\n P<\/jats:italic>\n = 0.042) and D\n f<\/jats:sub>\n (\n P<\/jats:italic>\n = 0.008), the latter reflecting larger, denser and more fibrin\u2010rich networks. We also observed selective shortening of activated partial thromboplastin time (aPTT) (\n P<\/jats:italic>\n = 0.018), indicating activation of the intrinsic coagulation pathway. This study provides the first\n in vivo<\/jats:italic>\n evidence that acute psychological stress triggers systemic free radical formation and drives prothrombotic remodelling of clot architecture. These findings identify oxidative stress as a mechanistic link between psychological stress and CVD risk and highlight it as a compelling target for prevention and therapy.\n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>\n \n Key points<\/jats:title>\n \n \n \n Although psychological stress is a recognised risk factor for cardiovascular disease (CVD), its mechanistic association with a hypercoagulable state remains unresolved.<\/jats:p>\n <\/jats:list-item>\n \n \n Acute psychological stress, induced by the Trier Social Stress Test (TSST), significantly increased systemic free radical formation, as measured by elevated levels of ascorbate free radical (A\n \u2022\u2212<\/jats:sup>\n ) via electron paramagnetic resonance (EPR) spectroscopy, and was associated with the formation of larger, denser, more fibrin\u2010rich clots confirmed by increased fractal dimension (D\n f<\/jats:sub>\n ).\n <\/jats:p>\n <\/jats:list-item>\n \n \n The concurrent increase in A\n \u2022\u2212<\/jats:sup>\n and D\n f<\/jats:sub>\n suggests that free radical\u2013mediated oxidative stress is an upstream driver of psychological stress\u2010induced activation of haemostasis, specifically altering clot quality.\n <\/jats:p>\n <\/jats:list-item>\n \n The TSST selectively shortened activated partial thromboplastin time (aPTT), indicating activation of the intrinsic\/contact coagulation pathway. There were no changes in prothrombin time (PT) or D\u2010dimer, suggesting haemostatic activation occurred without engaging fibrinolysis.<\/jats:p>\n <\/jats:list-item>\n \n The findings demonstrate that even a brief episode of emotional stress can increase thrombotic potential in healthy individuals and identify oxidative stress as a key mechanistic link and a potential therapeutic target for treating stress\u2010related CVD.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/jp290576","type":"journal-article","created":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T00:39:44Z","timestamp":1777163984000},"page":"4707-4716","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Psychological stress catalyses free radical\u2013mediated activation of coagulation in humans"],"prefix":"10.1113","volume":"604","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1515-0672","authenticated-orcid":false,"given":"Lewis","family":"Fall","sequence":"first","affiliation":[{"name":"Neurovascular Research Laboratory University of South Wales Pontypridd UK"},{"name":"Faculty of Computing, Engineering and Science University of South Wales Pontypridd UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1005-7038","authenticated-orcid":false,"given":"Benjamin S.","family":"Stacey","sequence":"additional","affiliation":[{"name":"Neurovascular Research Laboratory University of South Wales Pontypridd UK"},{"name":"Faculty of Life Sciences and Education University of South Wales Pontypridd UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elsie","family":"Swain","sequence":"additional","affiliation":[{"name":"Neurovascular Research Laboratory University of South Wales Pontypridd UK"},{"name":"Faculty of Computing, Engineering and Science University of South Wales Pontypridd UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ebony","family":"Samuel","sequence":"additional","affiliation":[{"name":"Neurovascular Research Laboratory University of South Wales Pontypridd UK"},{"name":"Faculty of Computing, Engineering and Science University of South Wales Pontypridd UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan","family":"Robinson","sequence":"additional","affiliation":[{"name":"Neurovascular Research Laboratory University of South Wales Pontypridd UK"},{"name":"Swansea University Medical School Swansea UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danny W.","family":"Walmsley","sequence":"additional","affiliation":[{"name":"Neurovascular Research Laboratory University of South Wales Pontypridd UK"},{"name":"Faculty of Life Sciences and Education University of South Wales Pontypridd UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Marley","sequence":"additional","affiliation":[{"name":"Neurovascular Research Laboratory University of South Wales Pontypridd UK"},{"name":"Faculty of Life Sciences and Education University of South Wales Pontypridd UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0097-0616","authenticated-orcid":false,"given":"Thomas S.","family":"Owens","sequence":"additional","affiliation":[{"name":"Neurovascular Research Laboratory University of South Wales Pontypridd UK"},{"name":"Faculty of Life Sciences and Education University of South Wales Pontypridd UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adnan","family":"Haq","sequence":"additional","affiliation":[{"name":"Neurovascular Research Laboratory University of South Wales Pontypridd UK"},{"name":"Faculty of Life Sciences and Education University of South Wales Pontypridd UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon G.","family":"Yandle","sequence":"additional","affiliation":[{"name":"Neurovascular Research Laboratory University of South Wales Pontypridd UK"},{"name":"Faculty of Life Sciences and Education University of South Wales Pontypridd UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Cox","sequence":"additional","affiliation":[{"name":"Neurovascular Research Laboratory University of South Wales Pontypridd UK"},{"name":"Faculty of Life Sciences and Education University of South Wales Pontypridd UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0498-7095","authenticated-orcid":false,"given":"Damian M.","family":"Bailey","sequence":"additional","affiliation":[{"name":"Neurovascular Research Laboratory University of South Wales Pontypridd UK"},{"name":"Faculty of Life Sciences and Education University of South Wales Pontypridd UK"},{"name":"Bexorg, Inc. 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