Treatment with Dicumarol in Small Continuous Doses

Abstract

Since dicumarol (3-3' methylen bis (4-hydroxycoumarin) = nSynparin)) (was used first in 1941 in anticoagulant therapy (2,5,8) intermittent application has been most frequently used. Treatment is begun with 50 to 75 centigram (cg) of dicuniarol by mouth, the effect of this initial dose on the prothrombin time is observed and treatment is then continued while daily readings of the prothrombin time are made. The characteristic feature of the treatment lies in the large maintenance *doses, frequently 25 cg dicumarol every time and the long intervals (often several days) between the doses. It is common experience (fig. 1) that this dosage makes it difficult to maintain the prothrombin time in what is considered as a therapeutically active zone. Variations frequently occur in the prothrombin index and the purpose of the treatment, which is the constant reduction of the coagulation of blood, is not maintained, or the danger of bleeding arises. Variations in the prothrombin index are particularly obvious when anticoagulant treatment is continued for a long period.Another form of dosage was therefore tried and it was hoped that it will provide easier maintenance of the prothrombin index in the therapeutically effective zone. In the literature little information is available regarding the forms of dosage other than the intermittent one which is generally used. Meyer, Bingham and ,4xelrod (1942) recommended after an initial dose of 5 mg per kg of bodyweight siiiall daily doses of 1.5 mg per kg. Their series comprises 14 patients, 10 of whom were treated for 8 days. I n other cases the treatment was continued longer, but could not be carried to its conclusion on account of a considerable rise in the prothrombin time. The maintenance dosage was probably too high. Bingham, Meyer and Howard (1943) who also reported a small series believed that a more .constsnt level of the plasma prothrombin can be obtained by the daily admini-