Abstract
During the course of a routine 28-day intravenous toxicity study in the rat, clinical haemorrage was noted from the injection sites of rats receiving the highest dose level. Subsequent investigations revealed the compound to be a potent platelet aggregating agent at the concentration used for this dose level, and a pattern of reaction was established which led to the diagnosis of disseminated intravascular coagulation (DIC), caused by the activation of platelets at the time of injection.
Of particular interest was the fact that, under the condition of the studies performed, the whole cycle (establishment of DIC, fibrinolysis and a return to normal values) was complete in less than one hour. The speed of this reaction raises the question as to the best time of sampling animals, in relation to dosing, during the course of a toxicity study.
The results from these studies suggest that samples taken at, or close to, the time of maximum blood level may provide information not apparent if the samples had been taken at any other time.
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Ganney, B.A., Brown, G. Disseminated intravascular coagulation in the rat: A case history from a toxicological study. Comparative Haematology International 1, 172–177 (1991). https://doi.org/10.1007/BF00515667
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DOI: https://doi.org/10.1007/BF00515667