{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T09:43:41Z","timestamp":1770975821642,"version":"3.50.1"},"reference-count":24,"publisher":"American Society of Hematology","issue":"7","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2002,4,1]]},"abstract":"<jats:p>Antithrombin (AT) deficiency is an autosomal disorder associated with venous thromboembolism. However, a diagnosis of homozygous AT deficiency is seldom made. Most patients are heterozygous and have approximately 50% AT activities, and they are at higher risk for the development of thromboembolism. Through gene targeting we generated AT-deficient mice and previously reported that completely AT-deficient mice could not survive the prenatal period because of extensive thrombosis in the myocardium and liver sinusoids. In contrast, heterozygous AT-deficient mice with 50% AT activities have not shown spontaneous thromboembolic episodes. To demonstrate a thrombotic tendency in heterozygous AT deficiency, we challenged heterozygous AT-deficient mice (AT+\/\u2212 mice) with the administration of lipopolysaccharide (LPS) or with restraint stress by immobilization. LPS injection markedly induced fibrin deposition in the kidney glomeruli, myocardium, and liver sinusoids in AT+\/\u2212 mice compared with wild-type mice (AT+\/+ mice). Restraint stress tests were performed by placing mice in 50-mL conical centrifuge tubes for 20 hours. Fibrin deposition was observed in the kidney ofAT+\/+ and AT+\/\u2212 mice, but AT+\/\u2212mice exhibited more extensive fibrin deposition thanAT+\/+ mice. After prophylactic administration of human AT concentrates to increase plasma AT activities of AT+\/\u2212mice, LPS-induced fibrin deposition was effectively prevented. These results suggest that heterozygous AT deficiency is significantly associated with a tendency toward thrombosis formation in the kidney. The AT+\/\u2212 mouse thus is a useful model for studying the effect of environmental or genetic risk factors on thrombogenesis.<\/jats:p>","DOI":"10.1182\/blood.v99.7.2455","type":"journal-article","created":{"date-parts":[[2002,10,11]],"date-time":"2002-10-11T18:33:52Z","timestamp":1034361232000},"page":"2455-2458","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":48,"title":["Impact of antithrombin deficiency in thrombogenesis: lipopolysaccharide and stress-induced thrombus formation in heterozygous antithrombin-deficient mice"],"prefix":"10.1182","volume":"99","author":[{"given":"Masamitsu","family":"Yanada","sequence":"first","affiliation":[{"name":"From the First Department of Internal Medicine, Department of Biochemistry, and Institute for Laboratory Animal Research, Nagoya University School of Medicine, and the Department of Medical Technology, Nagoya University School of Health Sciences, Nagoya National Hospital, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuhito","family":"Kojima","sequence":"additional","affiliation":[{"name":"From the First Department of Internal Medicine, Department of Biochemistry, and Institute for Laboratory Animal Research, Nagoya University School of Medicine, and the Department of Medical Technology, Nagoya University School of Health Sciences, Nagoya National Hospital, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuhiro","family":"Ishiguro","sequence":"additional","affiliation":[{"name":"From the First Department of Internal Medicine, Department of Biochemistry, and Institute for Laboratory Animal Research, Nagoya University School of Medicine, and the Department of Medical Technology, Nagoya University School of Health Sciences, Nagoya National Hospital, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukiko","family":"Nakayama","sequence":"additional","affiliation":[{"name":"From the First Department of Internal Medicine, Department of Biochemistry, and Institute for Laboratory Animal Research, Nagoya University School of Medicine, and the Department of Medical Technology, Nagoya University School of Health Sciences, Nagoya National Hospital, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koji","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"From the First Department of Internal Medicine, Department of Biochemistry, and Institute for Laboratory Animal Research, Nagoya University School of Medicine, and the Department of Medical Technology, Nagoya University School of Health Sciences, Nagoya National Hospital, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tadashi","family":"Matsushita","sequence":"additional","affiliation":[{"name":"From the First Department of Internal Medicine, Department of Biochemistry, and Institute for Laboratory Animal Research, Nagoya University School of Medicine, and the Department of Medical Technology, Nagoya University School of Health Sciences, Nagoya National Hospital, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenji","family":"Kadomatsu","sequence":"additional","affiliation":[{"name":"From the First Department of Internal Medicine, Department of Biochemistry, and Institute for Laboratory Animal Research, Nagoya University School of Medicine, and the Department of Medical Technology, Nagoya University School of Health Sciences, Nagoya National Hospital, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahiko","family":"Nishimura","sequence":"additional","affiliation":[{"name":"From the First Department of Internal Medicine, Department of Biochemistry, and Institute for Laboratory Animal Research, Nagoya University School of Medicine, and the Department of Medical Technology, Nagoya University School of Health Sciences, Nagoya National Hospital, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Muramatsu","sequence":"additional","affiliation":[{"name":"From the First Department of Internal Medicine, Department of Biochemistry, and Institute for Laboratory Animal Research, Nagoya University School of Medicine, and the Department of Medical Technology, Nagoya University School of Health Sciences, Nagoya National Hospital, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hidehiko","family":"Saito","sequence":"additional","affiliation":[{"name":"From the First Department of Internal Medicine, Department of Biochemistry, and Institute for Laboratory Animal Research, Nagoya University School of Medicine, and the Department of Medical Technology, Nagoya University School of Health Sciences, Nagoya National Hospital, 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