{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:44:25Z","timestamp":1790837065193,"version":"4.1.0"},"reference-count":44,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2024,2,2]]},"abstract":"<jats:p>Tissue factor pathway inhibitor \u03b1 (TFPI\u03b1) is the major physiological regulator of the initiation of blood coagulation. In vitro, TFPI\u03b1 anticoagulant function is enhanced by its cofactor, protein S. To define the role of protein S enhancement in TFPI\u03b1 anticoagulant function in vivo, we blocked endogenous TFPI in mice using a monoclonal antibody (14D1). This caused a profound increase in fibrin deposition using the laser injury thrombosis model. To explore the role of plasma TFPI\u03b1 in regulating thrombus formation, increasing concentrations of human TFPI\u03b1 were coinjected with 14D1, which dose-dependently reduced fibrin deposition. Inhibition of protein S cofactor function using recombinant C4b-binding protein \u03b2 chain significantly reduced the anticoagulant function of human TFPI\u03b1 in controlling fibrin deposition. We report an in vivo model that is sensitive to the anticoagulant properties of the TFPI\u03b1-protein S pathway and show the importance of protein S as a cofactor in the anticoagulant function of TFPI\u03b1 in vivo.<\/jats:p>","DOI":"10.1126\/sciadv.adk5836","type":"journal-article","created":{"date-parts":[[2024,2,2]],"date-time":"2024-02-02T18:58:50Z","timestamp":1706900330000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":15,"title":["TFPI\u03b1 anticoagulant function is highly dependent on protein S in vivo"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-3393-8099","authenticated-orcid":true,"given":"Anastasis","family":"Petri","sequence":"first","affiliation":[{"name":"Centre for Haematology, Hammersmith Hospital Campus, Imperial College London, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2736-4053","authenticated-orcid":true,"given":"Parvathy","family":"Sasikumar","sequence":"additional","affiliation":[{"name":"Centre for Haematology, Hammersmith Hospital Campus, Imperial College London, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia Badia","family":"Folgado","sequence":"additional","affiliation":[{"name":"Centre for Haematology, Hammersmith Hospital Campus, Imperial College London, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4789-203X","authenticated-orcid":true,"given":"David","family":"Jones","sequence":"additional","affiliation":[{"name":"Centre for Haematology, Hammersmith Hospital Campus, Imperial College London, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3865-1170","authenticated-orcid":true,"given":"Yaoxian","family":"Xu","sequence":"additional","affiliation":[{"name":"Centre for Haematology, Hammersmith Hospital Campus, Imperial College London, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5313-6508","authenticated-orcid":true,"given":"Josefin","family":"Ahnstr\u00f6m","sequence":"additional","affiliation":[{"name":"Centre for Haematology, Hammersmith Hospital Campus, Imperial College London, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7394-0587","authenticated-orcid":true,"given":"Isabelle I.","family":"Salles-Crawley","sequence":"additional","affiliation":[{"name":"Centre for Haematology, Hammersmith Hospital Campus, Imperial College London, London, UK."},{"name":"Vascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, St. George's University of London, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6723-7841","authenticated-orcid":true,"given":"James T. 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