Dicumarol Therapy

Abstract

One of the problems of Dicumarol administration has been determination of the adequacy of therapy. A fundamental stage in thrombus formation in the circulation is platelet clumping. Since platelets are involved in both hemostasis and thrombosis, a study of changes in platelet function may prove useful. The effects of Dicumarol on platelet clumping and adhesiveness have, therefore, been studied and related to changes in other clotting mechanisms. Comparison of platelet function in control periods and during Dicumarol administration shows that this drug lowers the adhesive index and prolongs the platelet clumping time to a highly significant degree. The accuracy of estimates of these 2 platelet functions given by 3 other tests, prothrombin time, whole blood clotting time and plasma activity in the thromboplastin generation tests have been compared. By any criterion, degree of correlation, consistency of regression slopes, intercepts or scatter about regression lines, clotting time was the most efficient of the 3 tests for evaluting platelet function. The prothrombin time was the least efficient. Furthermore, hemorrhage from excessive dosage was closely related to the platelet clumping time and clotting time. It should be pointed out, however, that in about one-third of the patients the prothrombin time was as good an index of platelet clumping time as clotting time. While prothrombin times done with 2 different sources of thromboplastin may give congruous results in untreated patients, considerable discrepancies may appear during Dicumarol therapy. If prothrombin time is to be used as a guide to Dicumarol therapy, it is important to establish in each patient separately its reliability as a measure of the behavior of the clotting mechanism as a whole. For those in whom it seems reliable, an individual "therapeutic range" should be determined. For other cases, some other suitable test should be employed. It is emphasized that regulation of Dicumarol dosage is an individual problem and that only those tests shown to be reliable indices of safe effective modifications of clotting mechanism in the individual patient should be used.

Effect of Smoking on Blood Coagulation and Platelet Survival in Man

“…If, indeed, smoking affects the arterial wall or endothelium, or blood coagulation, we might reasonably expect this to be reflected in the survival of the blood platelets. The greater part of the evidence indicates that diet influences in vitro tests of blood coagulation (Mustard, 1961), and we have recently shown that this is also true of platelet survival (Mustard and Murphy, 1962). It is therefore clearly important that studies such as the one reported in this paper should be done under *This study was supported in part by United States Public Health Grant H-4964, a grant from the Department of Veterans Affairs, and a grant from the Armour Pharmaceutical Company.…”

“…The techniques involved have already been described in detail (Murphy and Mustard, 1960). Samples of blood were taken daily during the 10-day period in which platelet survival was studied.…”

“…32p)* method of Leeksma and Cohen (1956), which we have previously described (Murphy and Mustard, 1961a). In this method platelets are tagged in vivo by this tenacious radioactive compound.…”

“…Only the upper half of the platelet button is suspended in distilled water. The methods and problems of computing platelet survival from the data have been discussed elsewhere (Murphy and Mustard 1961a, 1961b, Mustard and Murphy, 1962. There is controversy about the pattern which platelet survival follows.…”

“…Differences among subjects were in part due to the differences of the conditions under SMOKING AND BLOOD COAGULATION which they were maintained, in part to the nature of the patient's disease. Statistical Considerations.-We have shown elsewhere that the whole-blood clotting-time and the platelet clumping-time are log-normally distributed, the plasma thromboplastin tissue has a harmonic normal distribution, and the other variates are normally distributed Mustard, 1961a, 1961b). Appropriate transformations have been used in computing means and differences between groups, but mean values have been retransformed to the original scale before being entered in the tables.…”