Hepatocyte tissue factor contributes to the hypercoagulable state in a mouse model of chronic liver injury

Journal of Hepatology
Pierre-Emmanuel RautouNigel Mackman

Abstract

Patients with chronic liver disease and cirrhosis have a dysregulated coagulation system and are prone to thrombosis. The basis for this hypercoagulable state is not completely understood. Tissue factor (TF) is the primary initiator of coagulation in vivo. Patients with cirrhosis have increased TF activity in white blood cells and circulating microparticles. The aim of our study was to determine the contribution of TF to the hypercoagulable state in a mouse model of chronic liver injury. We measured levels of TF activity in the liver, white blood cells and circulating microparticles, and a marker of activation of coagulation (thrombin-antithrombin complexes (TATc)) in the plasma of mice subjected to bile duct ligation for 12days. We used wild-type mice, mice with a global TF deficiency (low TF mice), and mice deficient for TF in either myeloid cells (TF(flox/flox),LysMCre mice) or in hepatocytes (TF(flox/flox),AlbCre). Wild-type mice with liver injury had increased levels of white blood cell, microparticle TF activity and TATc compared to sham mice. Low TF mice and mice lacking TF in hepatocytes had reduced levels of TF in the liver and in microparticles and exhibited reduced activation of coagulation without a change in liver ...Continue Reading

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Citations

Jun 4, 2016·Blood·Ton Lisman
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Dec 12, 2017·Toxicological Sciences : an Official Journal of the Society of Toxicology·Anna K KopecJames P Luyendyk
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Aug 16, 2019·Arteriosclerosis, Thrombosis, and Vascular Biology·Kevin S BakerJames P Luyendyk
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Feb 25, 2020·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Maxime G ZermattenLorenzo Alberio
Aug 31, 2020·Research and Practice in Thrombosis and Haemostasis·Axel RosellNigel Mackman
Aug 17, 2018·European Journal of Gastroenterology & Hepatology·Nathalie I CaversaccioAnne Angelillo-Scherrer
Jul 19, 2020·Journal of Hepatology·Sara Thietart, Pierre-Emmanuel Rautou
Jun 5, 2021·Advanced Drug Delivery Reviews·Enis KostallariPierre-Emmanuel Rautou

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