Regulation of coagulation factors during liver regeneration in mice: mechanism of factor VIII elevation in plasma.

INTRODUCTIONS The profiles of coagulation factor production during liver regeneration process remains to be fully elucidated. The present study was aimed to perform a comprehensive analysis whether hepatic gene expression was differentially regulated relative to the secretion of biologically active coagulation factors using a mouse model of liver regeneration. MATERIALS AND METHODS Liver regeneration was induced by performing a 2/3 partial hepatectomy (PHx). Plasma samples were assessed for coagulation factor activities (fibrinogen, prothrombin, V, VII, VIII, IX, X, XI, XII, and XIII) and the liver mRNA levels of coagulation, anti-coagulation, and fibrinolytic factors were quantified by real-time RT-PCR during the phase of liver regeneration. RESULTS At the peak of liver regeneration, the expression levels for all of the genes analyzed were found to be reduced in a time-dependent manner. Consistent with the gene expression levels, plasma activities of all coagulation factors, except for FVIII, were temporally declined during the same time frame. FVIII paradoxically demonstrated a significant increase (P<0.05) in plasma activities concomitant with the decrease of liver mRNA expression levels. We found that the increase in plasma FVIII activities might be associated with (1) a delay in the inactivation of plasma FVIII caused by increased VWF in plasma and decreased FVIII clearance in the liver, (2) the rapid release of FVIII from the storage sites, and (3) the alteration of intracellular trafficking pathway of FVIII. CONCLUSIONS The present study demonstrated that the process of liver regeneration involves a general reduction for many of the coagulation cascade proteins, but there are paradoxical increases in plasma levels of FVIII and VWF.