{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T06:52:02Z","timestamp":1772952722249,"version":"3.50.1"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Antithrombin resistance (ATR) is a congenital thrombotic predisposition caused by abnormal prothrombin, FII (Factor II). Abnormal FII with ATR characteristics, when converted to thrombin, FIIa (Factor IIa), shows a reduced affinity of binding to AT (antithrombin), resulting in reduced anti-FIIa and a thrombotic tendency. Data on the efficacy of anticoagulants in ATR are currently insufficient.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>Mouse models of ATR were generated to investigate the efficacy of anticoagulants. Because FII R596L, which causes ATR in humans, was considered to correspond to R593L in mice based on gene sequence analysis, knock-in mice that systemically express FII R593L were generated. First, the nature of ATR was confirmed by blood coagulation analysis. We then evaluated thrombotic tendency at the individual level using an inferior vena cava stenosis model, and evaluated the antithrombotic effects of unfractionated heparin, low molecular weight heparin, synthetic pentasaccharide, and direct oral anticoagulants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>In coagulation studies, R593L Homo and Hetero mice (R593L Homo and Hetero, respectively) exhibited lower FII antigen levels and lower FIIa generation potential than wild-type mice, but residual FIIa activity after addition of AT confirmed the presence of ATR properties. In the inferior vena cava stenosis model, significantly higher thrombus formation was maintained in R593L Homo and Hetero compared with wild-type, even 96 hours after inferior vena cava stenosis. In anticoagulant administration experiments, anticoagulants with anti-FIIa effects appeared more effective against FII R593L.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Knock-in of FII R593L produced ATR model mice, which showed a strong thrombotic tendency. Evaluation of antithrombotic therapies showed that anticoagulants with anti-FIIa effects were highly effective.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/atvbaha.125.324007","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T10:00:20Z","timestamp":1767866420000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Antithrombotic Therapy on Antithrombin Resistance in a Mouse Model"],"prefix":"10.1161","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2250-7964","authenticated-orcid":true,"given":"Nobuaki","family":"Suzuki","sequence":"first","affiliation":[{"name":"Department of Transfusion Medicine (Nobuaki Suzuki, T.M.), Nagoya University Hospital, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7194-3183","authenticated-orcid":true,"given":"Atsuo","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Medical Technique (A.S.), Nagoya University Hospital, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4960-1400","authenticated-orcid":true,"given":"Shogo","family":"Tamura","sequence":"additional","affiliation":[{"name":"Division of Cellular and Genetic Sciences, Department of Integrated Health Sciences (S. Tamura, S. Tokumaru, A.T., S.S., S.O., F.H., T. Kojima), Nagoya University Graduate School of Medicine, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sena","family":"Tokumaru","sequence":"additional","affiliation":[{"name":"Division of Cellular and Genetic Sciences, Department of Integrated Health Sciences (S. Tamura, S. Tokumaru, A.T., S.S., S.O., F.H., T. Kojima), Nagoya University Graduate School of Medicine, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7267-2751","authenticated-orcid":true,"given":"Hinako","family":"Notoh","sequence":"additional","affiliation":[{"name":"Graduate School of Health Sciences, Hokkaido University, Sapporo, Japan (H.N.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akira","family":"Takagi","sequence":"additional","affiliation":[{"name":"Division of Cellular and Genetic Sciences, Department of Integrated Health Sciences (S. Tamura, S. 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