In their studies on the causative agent of the hemorrhagic sweet clover disease, dicumarol, 3-3'-methylenebis-(4-hydroxycoumarin), Link and his students found that the prothrombinopenia inducing agent is active in vivo only and that a latent period exists before the prothrombinopenia becomes detectable. These facts led to the thesis that the delayed action occurs, at least in part, because the methylene bis-coumarin must first be metabolized in the body to a derivative which is, or from which is liberated, the effective agent. The quantitative degradation of dicumarol to 2 mols of salicylic acid prompted the agricultural chemists to study the action of salicylic acid on the prothrombin level (or activity) of the blood. They demonstrated in rats that salicylic acid can induce prothrombinopenia and that such prothrombinopenia can be prevented by vitamin K.1
Following this, investigations conducted by Meyer and Howard2 and by Shapiro, Redish and Campbell3 established that
SHAPIRO S. STUDIES ON PROTHROMBINVI. THE EFFECT OF SYNTHETIC VITAMIN K ON THE PROTHROMBINOPENIA INDUCED BY SALICYLATE IN MAN. JAMA. 1944;125(8):546–548. doi:10.1001/jama.1944.02850260020006
Customize your JAMA Network experience by selecting one or more topics from the list below.