Decreased factor VIII levels during acetaminophen-induced murine fulminant hepatic failure
| Autor: | Ernest T. Parker, Christopher B. Doering, Pete Lollar, Christopher E. Nichols |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Male
congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty acetaminophen overdose animal diseases Fulminant Immunology Biochemistry Mice Fulminant hepatic failure Von Willebrand factor hemic and lymphatic diseases Internal medicine von Willebrand Factor Medicine Animals Humans Acetaminophen Factor VIII biology business.industry Cell Biology Hematology Analgesics Non-Narcotic Pathophysiology Mice Inbred C57BL Disease Models Animal Endocrinology Liver Hemostasis Toxicity biology.protein business Liver Failure medicine.drug |
| Zdroj: | Blood. 102(5) |
| ISSN: | 0006-4971 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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