The relationship between blood coagulation and hepatic damage is well established but has been largely ignored as a means of detecting hepatotoxicity in regulatory safety evaluation, especially in rodent studies. In the main this has been due to the limitations of the laboratory techniques available for the assessment of clotting times in small amounts of blood.
Carbon tetrachloride and butylated hydroxytoluene (BHT) were chosen as model hepatotoxic compounds and administered at doses designed to produce liver damage within 24 h. Classic centrilobular necrosis was induced with carbon tetrachloride but the effect of BHT was negligible, contrary to published evidence. The clotting potential was monitored by means of the standard one-stage prothrombin time using species-homologous brain reagent and by a modified commercially available reagent (Thrombotest) which is more specific for the coagulation factors involved with the one-stage reaction. Thrombotest was demonstrated to be more sensitive than the conventional one-stage prothrombin time method and to have a number of clear practical advantages for use with small rodents. Its use in regulatory toxicology is recommended.
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Schofield, M.A., Hall, D.E. Detection of hepatotoxicity by means of blood coagulation changes. Comparative Haematology International 1, 200–204 (1991). https://doi.org/10.1007/BF00235370
- Prothrombin time
- Blood coagulation