{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T04:38:08Z","timestamp":1780634288812,"version":"3.54.1"},"reference-count":20,"publisher":"American Society of Hematology","issue":"23","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,6,4]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Hypofibrinogenemia reduces experimental venous thrombosis, but the impact on arterial thrombosis remains unknown. In a cohort of patients with congenital fibrinogen disorders, 19 of 264 (\u223c7%) patients developed arterial thrombosis, including 4 of 41 (\u223c10%) patients with hypofibrinogenemia. However, 0 of 8 patients with fibrinogen \u03b1C-region truncation mutations reported arterial thrombosis over 286 patient-years. To analyze the impact of hypofibrinogenemia and the fibrinogen \u03b1C region on arterial thrombosis, 2 mouse models were employed: (1) wild-type mice treated with lipid nanoparticles encapsulating small interfering RNA against fibrinogen (siFga) and (2) Fga270\/270 hypofibrinogenemic mice expressing fibrinogen with a truncated \u03b1C region. Although siFga-treated hypofibrinogenemic mice developed occlusive carotid artery thrombi similarly to controls, Fga270\/270 mice displayed suppressed carotid thrombosis following FeCl3 challenge, indicating loss of the \u03b1C region but not hypofibrinogenemia alone reduces arterial thrombosis. To determine if protection from arterial thrombosis in Fga270\/270 mice was linked to loss of \u03b1C-region\u2013platelet glycoprotein VI receptor (GPVI) interaction, platelet GPVI was depleted by JAQ1 antibody administration. JAQ1-treated wild-type mice were protected from arterial thrombosis following 5% FeCl3 but not 10% FeCl3 challenge. Interestingly, JAQ1 administration suppressed arterial thrombosis in siFga-treated mice but did not enhance protection in Fga270\/270 mice following 10% FeCl3 challenge. Our studies suggest the fibrinogen \u03b1C region promotes arterial thrombosis in hypofibrinogenemic conditions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2025031456","type":"journal-article","created":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T17:56:13Z","timestamp":1772819773000},"page":"2821-2827","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":1,"title":["The fibrinogen \u03b1C region promotes arterial thrombosis in the context of hypofibrinogenemia"],"prefix":"10.1182","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9871-0593","authenticated-orcid":false,"given":"Robert H.","family":"Lee","sequence":"first","affiliation":[{"name":"1Department of Biochemistry and Biophysics, The University of North Carolina at Chapel Hill, Chapel Hill, NC"},{"name":"2UNC Blood Research Center, The University of North Carolina at Chapel Hill, Chapel Hill, 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J.","family":"Kastrup","sequence":"additional","affiliation":[{"name":"3Department of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, BC, Canada"},{"name":"4Versiti Blood Research Institute, Milwaukee, WI"},{"name":"10Department of Surgery, Medical College of Wisconsin, Milwaukee, WI"},{"name":"11Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI"},{"name":"12Department of Biomedical Engineering, Medical College of Wisconsin, Milwaukee, WI"},{"name":"13Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1211-8861","authenticated-orcid":false,"given":"Wolfgang","family":"Bergmeier","sequence":"additional","affiliation":[{"name":"1Department of Biochemistry and Biophysics, The University of North Carolina at Chapel Hill, Chapel Hill, NC"},{"name":"2UNC Blood Research Center, The University of North 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