Arnold G. Ware

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.

Stability of serum Ac-globulin.

Serum Ac-globulin is a clotting factor found in the globulin fraction of blood serum 1 , 2 which accelerates the change of prothrombin to thrombin. This factor is present in plasma in a much less active form, plasma Ac-globulin, 3 , 4 , 5 , 6 7 which serves as a precursor to serum Ac-globulin. The role of Ac-globulin in the total clotting reaction has been described as follows: 1 , 2 The clotting reaction is initiated by thromboplastin, which, in the presence of calcium ions, interacts with prothrombin to form thrombin. The thrombin in turn alters the plasma Ac-globulin so that it becomes serum Ac-globulin. The latter then intensifies the reaction between thromboplastin and prothrombin. Clotting is then accomplished by the action of thrombin on fibrinogen. In the developmental work on Ac-globulin, oxalated bovine plasma was used as a potent stable source of plasma Ac-globulin 8 and bovine serum 1 a stable source of serum Ac-globulin. In working with the sera of other species involving man, dog, and guinea pig, we have found that while plasma Ac-globulin is relatively stable, serum Ac-globulin is inactivated and largely disappears within a few hours after the blood is drawn. Rabbit serum Ac-globulin is similar to bovine serum Ac-globulin in that it remains stable for longer periods of time. In the study of the stability of serum Ac-globulin, blood was drawn and immediately centrifuged at 3,000 rpm for 10 minutes, and the serum was removed and stored at 5° C. Samples were analyzed for serum Ac-globulin by methods elsewhere described 1 after storage for periods of 15, 90, 180 and 300 minutes, as indicated in Fig. 1. In this procedure, human serum diluted 1,400 times was incubated for varying time intervals (as indicated on the horizontal axis, Fig. 1) with purified bovine prothrombin 9 and with optimal concentrations of thromboplastin and calcium.