Decreased factor VIII levels during acetaminophen-induced murine fulminant hepatic failure.
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 nonhepatocytic 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.
Doering
Christopher B
CB
Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA.
Parker
Ernest T
ET
Nichols
Christopher E
CE
Lollar
Pete
P
D000082:Acetaminophen / Q000506:poisoning*; D018712:Analgesics, Non-Narcotic / Q000506:poisoning*; D000818:Animals; D004195:Disease Models, Animal; D005169:Factor VIII / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism; D017093:Liver Failure / Q000139:chemically induced* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014841:von Willebrand Factor / Q000378:metabolism
D018712:Analgesics, Non-Narcotic; D014841:von Willebrand Factor; D000082:Acetaminophen; D005169:Factor VIII