{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T07:03:30Z","timestamp":1792047810268,"version":"4.4.0"},"reference-count":58,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Factor XII is a molecule of unclear physiological function that has attracted increasing research interest across multiple medical disciplines. In recent years, a substantial body of evidence has emerged regarding the contribution of factor XII to the pathogenesis of inflammatory and prothrombotic conditions. FXII has been shown to play a protective role in FXII-driven coagulation during host defence against infections and to protect against multi-organ failure in animal models of sepsis. In acute respiratory distress syndrome (ARDS), FXII activity contributes to the release of pro-inflammatory mediators and is associated with severe clinical outcomes; it also induces fibroblast migration in idiopathic pulmonary fibrosis. FXII deficiency has been associated with reduced neutrophil adhesion and migration in sterile skin wounds and immune complex-induced vasculitis. In neurological conditions, FXII deficiency significantly reduced the number and severity of multiple sclerosis relapses and decreased the volume of post-traumatic brain oedema. In heart failure pathogenesis, FXII deficiency and pharmacological inhibition of FXII activity blocked activation of the renin\u2013angiotensin\u2013aldosterone system (RAAS) in dilated cardiomyopathy, increased median survival, and delayed heart failure onset in murine models. Importantly, FXII inhibition prevented arterial thrombosis without affecting haemostasis. This review summarises the latest findings on the contribution of FXII to inflammatory and prothrombotic states across multiple medical fields, including cardiology. Pharmacological inhibition of FXII has generated considerable interest as a potential future therapeutic strategy; however, to date, human studies remain limited.<\/jats:p>","DOI":"10.3390\/ijms27031331","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T08:12:23Z","timestamp":1769674343000},"page":"1331","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Factor XII\u2014A New Therapeutic Target? A Systematic Review"],"prefix":"10.3390","volume":"27","author":[{"given":"Katarzyna","family":"Krajewska","sequence":"first","affiliation":[{"name":"Department of Cardiology, Teaching Hospital in Bialystok, Medical University of Bialystok, 15-276 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5277-9816","authenticated-orcid":false,"given":"Joanna","family":"Pawlus","sequence":"additional","affiliation":[{"name":"Department of Haematology Diagnostics, Teaching Hospital in Bialystok, Medical University of Bialystok, 15-276 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6457-704X","authenticated-orcid":false,"given":"Katarzyna","family":"Ptaszynska","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Teaching Hospital in Bialystok, Medical University of Bialystok, 15-276 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Lisowska","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Teaching Hospital in Bialystok, Medical University of Bialystok, 15-276 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1172\/JCI103109","article-title":"A familial hemorrhagic trait associated with a deficiency of a clot-promoting fraction of plasma","volume":"34","author":"Ratnoff","year":"1955","journal-title":"J. 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