The Comparative Action of Dicumarol and of Phenylindanedione on the Coagulase Reacting Factor and on Prothrombin *

Recent studies' have established the presence of a factor ("activator," Coagulase-reacting factor, or CRF) in plasma which is required for the coagulation of blood by staphylocoagulase. Maximum CRF activity resides in the globulin fractions of plasma, and separation from prothrombin is best achieved by repeated Seitz filtration.10 The filtration involves different rates of adsorption of prothrombin and CRF," so that when the filtrate is essentially devoid of prothrombin it still may possess substantial CRF activity. Efforts to identify CRF with factors at present known to participate in physiological clotting of blood have been unsuccessful,10'11 and the hypothesis has been proposed that the coagulase-CRF reaction bypasses the currently accepted pathways functioning in physiological clotting. The many points of resemblance between prothrombin and CRF, as well as the differences, have been discussed elsewhere."11 Duthie and Lorenz' find it tempting to consider prothrombin and CRF as identical. They point to similarities in physical properties, parallel losses of both prothrombin and CRF when prothrombin is converted to thrombin, to localization in comparable fractions of plasma, and to the finding that the concentration of both prothrombin and CRF decrease "almost pari passu" following dicumarol administration in rabbits. To explain the separation of CRF from prothrombin by Seitz filtration, they suggest that this procedure may not actually remove prothrombin, but that the physical structure of prothrombin is so altered that it can no longer be converted to thrombin while it continues to function as a coagulase ''activator." The observations of Duthie and Lorenz that dicumarol administration depresses CRF activity have been confirmed in this laboratory, both in rabbits and in patients undergoing dicumarol therapy for thrombotic disease. On the other hand, Miale' failed to note any effect on CRF levels of plasma of 21 patients on a dicumarol regime. The present study was undertaken to resolve this conflict, particularly since it seemed possible that a detailed quantitative analysis of the effect of dicumarol and related compounds on