The Effect of Intravenous Injection of Purified Human Tissue Thromboplastin in Rats

Abstract

As a background for the development and testing of phospholipase C in the therapy of post-traumatic and post-surgical intravascular coagulation in humans, highly purified tissue thromboplastin was injected i.v. into rats. The levels of factors V, VII, VIII and blood platelets and the activity of the intrinsic coagulation pathway in general (the cephalin test) were followed. Histological examination of pulmonary, kidney and liver tissue was carried out. The dose-response was highly dependent on the injection rate. A marked activation of factor VII and a fall in the activities of factors V and VIII as well as in thrombocyte counts were observed. Very few or no thrombi were seen beyond the pulmonary circulation. The main changes (fibrin-containing thrombi and platelet aggregates) were observed in the lungs during the 1st 15 min after injection. After 15 min virtually no thrombi or platelet aggregates could be detected. The effect of tissue thromboplastin was counteracted by large doses of antithrombin III.