Submitted March 18, 2003
Accepted April 22, 2003
Decreased factor VIII levels during acetaminophen-induced murine fulminant hepatic failure
Christopher B Doering, Ernest T Parker, Christopher E Nichols, and Pete Lollar*
Winship Cancer Institute, Emory University, Atlanta, GA, USA
* Corresponding author; email: jlollar{at}emory.edu.
During human fulminant hepatic failure (FHF), circulating levels of most hemostatic proteins fall dramatically. Concurrently factor VIII (fVIII) procoagulant activity rises despite destruction of the hepatocytes considered responsible for fVIII synthesis. This observation suggests a role for cells other than hepatocytes in fVIII biosynthesis during FHF. We have attempted to identify non-hepatocytic sites of fVIII biosynthesis by inducing FHF in mice using acetaminophen overdose, a common cause of human FHF. Acetaminophen treated mice consistently displayed signs characteristic of FHF including elevated plasma aminotransferase activity. However, acetaminophen treated mice demonstrated markedly reduced fVIII activity, contrary to the observation in human FHF. von Willebrand factor antigen levels were only mildly reduced, suggesting that the decrease in fVIII is not secondary to loss of von Willebrand factor. These results imply that there are fundamental differences in the regulation of plasma fVIII levels between humans and mice.
