Studies on the Anticoagulant 3,3 -Methylene-Bis- (4-Hydroxycoumarin)

Continents and Summary

3,3′-methyIene-bis-(4-hydroxycoumarin), Dicumarol, was shown in our experiments to be able to greatly reduce the incidence and degree of thrombus formation following the intravenous injection of Monolate in dogs. In dogs and monkeys some signs of necrosis of the liver were found in a number of animals, but since most of them suffered from a severe anemia, the significance of this finding is questionable. The livers of guinea pigs treated with the sweet clover factor showed changes as they occur in vitamin C-depleted animals. Intravenous glucose tolerance and bromsulfalein retention tests failed to show liver damage in animals not suffering from bleeding due to the administration of the drug. While this is in agreement with clinical findings, further studies of the physiology of this substance with particular reference to liver function appear indicated.

Our present experience shows that there is a considerable difference in tolerance between various species of animals and also among the individuals of the same species. The observation that single blood transfusions in dogs in a state of extreme depression of the pro-thrombin level were of only temporary benefit, is paralleled by similar clinical findings 11 , 8 and calls for particular care in avoiding excessively high dosage.