The nature of the heterogeneity of prothrombin during dicoumarol therapy.

Abstract

THE effect of the dicoumarol drugs on clotting factor biosynthesis is similar to that of vitamin K deficiency, in that the coagulant activities of clotting Factors II, VII, IX and X in the plasma are reduced. Also, levels are rapidly restored by the administration of vitamin K. The burst of clotting factor synthesis immediately following vitamin K treatment can take place even in the presence of antibiotics which inhibit general protein synthesis in the liver1. This suggests that vitamin K may act at a stage after peptide chain completion, such as the formation of intramolecular disulphide bridges, attachment of carbohydrate or secretion of the glycoprotein into the plasma. If antagonists of vitamin K interfere with the completion of the clotting proteins, incomplete forms may be present in the plasma during dicoumarol therapy and the nature of these forms may give a clue to the action of vitamin K. To test this hypothesis we have isolated the prothrombin of patients receiving dicoumarol therapy and investigated some of its properties.