John H. Olwin

Clinical Experience with a New Anticoagulant, Dipaxin (2-diphenylacetyl-l,3-indandione)

Prothrombin levels as measured by the one-stage whole-plasma and the two-stage technics were followed in 80 patients receiving Dipaxin. The induction period is similar to that for Tromexan, namely, 48 to 60 hours and the recovery period 10 to 15 days which is somewhat longer than in the case of either Tromexan or Dicumarol. This recovery period is hastened to some degree by the administration of water-soluble vitamin K preparations and materially accelerated by vitamin K1. The prothrombin level during maintenance therapy is unusually stable. Transient bleeding occurred in two patients. No other toxic effects were observed.

Effect of dicumarol on Ac-globulin and prothrombin activity.

Summary In human patients receiving dicumarol the plasma Ac-globulin level may be depressed by 20-50% following initiation of therapy. Individual variation was noteworthy. A gradual return to normal concentrations of Ac-globulin occurs within 3 weeks as therapy is continued and the prothrombin is maintained at a low titer. No appreciable difference from normal was found in the Ac-globulin values of patients who had been on dicumarol therapy for 1 to 14 months. Dogs receiving larger dicumarol doses than were administered to human patients showed a similar Ac-globulin response and a more marked reduction in prothrombin. A period of slightly lowered Ac-globulin activity in the dog is followed by a temporary rise to levels above normal.

Further Considerations on the Indications for and Limitations of Direct Surgery in Arteriosclerosis

Segmental obstruction due to arteriosclerosis may occur in peripheral arteries. Further experience in resection of these obstructed segments and their replacement by vein grafts is reported. Replacement of segments of the femoral artery has been accomplished in 30 patients. The proper selection of patients is essential for success. The various causes of failure and the limitations of the procedure are emphasized.

Dicumarol and Plasma Antithrombin Activity.

Summary With the administration of dicumarol to dogs there are no significant changes in the activity of antithrombin-II, and -III. Antithrombin-IV activity remained but no accurate quantitative measurements were made. In human subjects antithrombin-IV activity also remains and is probably not decreased. The thrombin-titer method of analysis shows that there are very marked changes in the activation rate of prothrombin soon after dicumarol is administered to human subjects. The addition of purfied prothrombin does not restore the activation rate to normal. In contrast to human subjects the activation rate of prothrombin is not reduced in dog plasma when dicumarol is administered.

USE OF ANTICOAGULANTS: PRO AND CON.

The panelists devote a large part of this discussion to answering direct questions relating to the use of anticoagulants. Among the problems considered are the advisability of anticoagulant therapy in acute myocardial infarction and after the acute episode, steps to be taken when a major operation or dental extraction is necessary, variations in response among different patients and at different times in the same patient, the duration of use of anticoagulants, the range of prothrombin time or level that constitutes the “therapeutic range,” and instructions for the patient in the event of hemorrhage at a time when medical help is not immediately available.