Thromboembolism and thromboembolic diseased states continue to be one of the major problems of clinical medicine. The potential hazards of thrombotic episodes and the frequent sequelae of chronic phlebitic processes render the effective use of anticoagulant drugs an increasingly important part of the clinician's therapeutic armamentarium. Such use is dependent upon the availability of anticoagulant drugs with clinically dependable pharmacological properties and on reliable assay procedures by which therapy with such drugs can be followed and controlled. A number of prothrombin depressants have been developed in the past 15 years, and of these, acenocoumarin (Sintrom) is one of the more recent ones. It is a nonhygroscopic light crystalline powder which is odorless and tasteless and is supplied for clinical use as 4 mg. scored tablets. It is stable under normal storage conditions and reacts as a weak acid. Chemically it is 3-(\g=a\acetonyl -4\x=req-\ nitro-benzyl) 4-hydroxycoumarin.The purpose of this paper is to report our clinical experience with 90 patients who were maintained with acenocoumarin therapy. Plasma prothrombin levels were followed with the one-stage and two-stage prothrombin assays in parallel. In a number of instances, additional prothrombin deter¬ minations were also carried out with the recently described TAMe (/>-toluenesulfonyl-1-arginine methyl ester) assay.10 The effects of the drug on plasma Ac globulin ( Factor V), SPCA (Factor VII), and autoprothrombin II (Factor IX, PTC) were studied in a small group of patients.
Methods and MaterialsBlood was collected by the two-syringe technique, nine parts being added immediately to one part of 3.2% sodium citrate. All prothrombin analyses were made within four hours of the collection of blood, whereas Ac globulin, Factor VII, and autoprothrombin II determinations were carried out on plasma samples which had been stored at -40 C for a period of up to two months. The results of the modified two-stage prothrombin assay of Ware and Seegers11 were used to control the administration of acenocoumarin. The one-stage assay of Quick12 was run in parallel, thromboplastin (Soluplastin *) being used in place of rabbitbrain extract. The TAMe assay for prothrombin was carried out according