Abstract
Several observations suggest that other factors besides the interference with the formation of prothrombin 1 must be considered in the pathogenesis of the bleeding‘tendency produced by dicumarol. Widespread dilatation of capillaries, arterioles and venules has been found, indicating that the hemorrhagic condition is due, at least in part, to vascular damage. 2 Moreover, other factors of the normal mechanism of coagulation have been found to be affected by dicumarol. Adhesiveness of the platelets is decreased 3 , 4 and the minimum requirement of calcium for optimum prothrombin time is increased 5 , 6 during the administration of the drug.
Evidence has been obtained which indicates that dicumarol causes changes in the thromboplastic activity of tissues. Dycker-hoff claims that dicumarol inhibits the first phase of coagulation by depressing the activity of thrombokinase. Recently Bose 8 has shown that thromboplastin prepared from desiccated brain of rabbits which have been fed 10 mg of dicumarol for 3 days is less active than that prepared from normal brains when tested on normal rabbit plasma using the prothrombin time technic.
In the present report, thromboplastic activity of rabbit brain obtained from animals severely poisoned by dicumarol has been studied by the prothrombin time method of Quick, but using a standard series of dilutions of CaCl2. Plasma from men and from normal and dicumarol-treated dogs and rabbits was employed.
Experimental. Ten full grown male rabbits in good state of nutrition were given dicumarol |3,3′-methylenbis (4-hydroxycou-marin)| until the prothrombin level was so depressed that they either died from hemorrhage or their prothrombin time and coagulation time were so delayed that neither one could any longer be determined satisfactorily. The drug was administered in doses of 5 mg per kg of body weight per day. In some animals the drug was administered orally as a gum acacia suspension
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