Carbon tetrachloride (CCl4)-induced liver injury activates hepatocyte-independent tissue factor-driven coagulation

BACKGROUND: Liver injury is associated with activation of the blood coagulation cascade. Hepatocytes express low levels of tissue factor (TF), the transmembrane receptor and cofactor for coagulation factor VIIa (FVIIa). The TF-FVIIa complex activates the extrinsic coagulation pathway and plays an essential role in hemostasis. OBJECTIVES: This study tested the hypothesis that hepatocyte TF drives coagulation activation after toxicant-induced liver injury. Liver injury and coagulation parameters were evaluated 2 to 96 hours after challenge. In separate studies, mice were challenged twice weekly for 4 to 6 weeks, and samples were collected 24 to 72 hours after the final challenge. RESULTS: challenge, whole-body TF deficiency significantly reduced coagulation activation and modestly decreased fibrosis by means of reduced hepatic stellate cell activation, but hepatocyte TF deficiency did not affect coagulation activation or liver fibrosis. Our findings provide the foundation for future work to identify TF-expressing cell types and their underlying contributions to liver injury pathogenesis.