Experimentally Induced Changes in Thi: Prothrombin Level of the Blood

The great advances that have been made in recent years in the study of the coagulation reaction of the blood have come about largely from work done on prothrombin. In order that this progress continue, greater insistence on accuracy in the determination of prothrombin must be made and a more comprehensive view of the nature of prothrombin should be adopted. According to the evidence of the writer (1) prothrombin is a complex consisting of calcium and two components. Dicumarol, a drug which depresses prothrombin activity, does so by causing a reduction of one of these essential components, which has been designated as Component B. On the basis of this concept, it is possible to st.udy more critically prothrombin activity following the administration of dicumarol. As a preliminary step certain basic factors such as the choice of animals, a correlation of the prothrombin level and the coagulability of the blood, and the effect of dosage were studied, and these result,s are presented in Part I of this paper. Selection of Animals-The rabbit and the dog are the most suitable of t’he common laboratory animals for studying the effect of dicumarol. Both respond readily either to the oral or to the intravenous administration of the drug, as Link and his associates (2) have shown, blood is easily obtainable routinely by venipuncture, and rabbit brain thromboplastin is a specific activator of the prothrombin in both species. The chief disadvantage is that the prothrombin level of rabbit and dog blood is approximately 5 times that of human blood (3) and that, if this divergency is not fully considered when interpreting the results obtained in these animals in terms of human clinical problems, much confusion can result. Limited studies suggest that the cat is even more susceptible to dicu-