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J Hepatol. 2016 Jan;64(1):53-9. doi: 10.1016/j.jhep.2015.08.017. Epub 2015 Aug 29.

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

Author information

1
Department of Medicine, Division of Hematology and Oncology, McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Service d'Hépatologie, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France. Electronic address: pierre-emmanuel.rautou@inserm.fr.
2
Department of Medicine, Division of Hematology and Oncology, McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
3
Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
4
Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI, USA.

Abstract

BACKGROUND & AIMS:

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.

METHODS:

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).

RESULTS:

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 fibrosis. In contrast, mice lacking TF in myeloid cells had reduced white blood cell TF but no change in microparticle TF activity or TATc.

CONCLUSIONS:

Hepatocyte TF activates coagulation in a mouse model of chronic liver injury. TF may contribute to the hypercoagulable state associated with chronic liver diseases in patients.

KEYWORDS:

Coagulation; Liver injury; Microparticle; Thrombosis

PMID:
26325534
PMCID:
PMC4691429
DOI:
10.1016/j.jhep.2015.08.017
[Indexed for MEDLINE]
Free PMC Article

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