{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:52:08Z","timestamp":1791219128825,"version":"4.1.0"},"reference-count":244,"publisher":"Portland Press Ltd.","issue":"24","license":[{"start":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T00:00:00Z","timestamp":1671148800000},"content-version":"vor","delay-in-days":15,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,12,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Inflammatory disease is often associated with an increased incidence of venous thromboembolism in affected patients, although in most instances, the mechanistic basis for this increased thrombogenicity remains poorly understood. Acute infection, as exemplified by sepsis, malaria and most recently, COVID-19, drives \u2018immunothrombosis\u2019, where the immune defence response to capture and neutralise invading pathogens causes concurrent activation of deleterious prothrombotic cellular and biological responses. Moreover, dysregulated innate and adaptive immune responses in patients with chronic inflammatory conditions, such as inflammatory bowel disease, allergies, and neurodegenerative disorders, are now recognised to occur in parallel with activation of coagulation. In this review, we describe the detailed cellular and biochemical mechanisms that cause inflammation-driven haemostatic dysregulation, including aberrant contact pathway activation, increased tissue factor activity and release, innate immune cell activation and programmed cell death, and T cell-mediated changes in thrombus resolution. In addition, we consider how lifestyle changes increasingly associated with modern life, such as circadian rhythm disruption, chronic stress and old age, are increasingly implicated in unbalancing haemostasis. Finally, we describe the emergence of potential therapies with broad-ranging immunothrombotic functions, and how drug development in this area is challenged by our nascent understanding of the key molecular and cellular parameters that control the shared nodes of proinflammatory and procoagulant pathways. Despite the increasing recognition and understanding of the prothrombotic nature of inflammatory disease, significant challenges remain in effectively managing affected patients, and new therapeutic approaches to curtail the key pathogenic steps in immune response-driven thrombosis are urgently required.<\/jats:p>","DOI":"10.1042\/cs20220208","type":"journal-article","created":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T03:29:00Z","timestamp":1671161340000},"page":"1809-1829","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Dysregulated haemostasis in thrombo-inflammatory disease"],"prefix":"10.1042","volume":"136","author":[{"given":"Paula\u00a0A.","family":"Klavina","sequence":"first","affiliation":[{"name":"1Irish Centre of Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma","family":"Leon","sequence":"additional","affiliation":[{"name":"1Irish Centre of Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland"},{"name":"2National Children\u2019s Research Centre, Our Lady\u2019s Children\u2019s Hospital Crumlin, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie\u00a0M.","family":"Curtis","sequence":"additional","affiliation":[{"name":"1Irish Centre of Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger\u00a0J.S.","family":"Preston","sequence":"additional","affiliation":[{"name":"1Irish Centre of Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland"},{"name":"2National Children\u2019s Research Centre, Our Lady\u2019s Children\u2019s Hospital Crumlin, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2022,12,16]]},"reference":[{"key":"2022121608284943500_B1","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1111\/bjh.15872","article-title":"Advances in understanding the molecular mechanisms that maintain normal haemostasis","volume":"186","author":"O'Donnell","year":"2019","journal-title":"Br. 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