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Sodium orthovanadate (vanadate) prolonged the clotting time of normal human plasma in a dose-dependent manner. The prolongation of clotting time by vanadate linearly decreased with an increase in the concentration of amiloride. Vanadate also was completely additive to prolongation by heparin. When factor Xa or thrombin was incubated with vanadate, the amidolytic activity of each decreased in a dose-dependent manner with vanadate. Amiloride protected the decrease of amidolytic activity of both factor Xa and thrombin by vanadate. The amidolytic activity of trypsin also was inhibited by vanadate, but that of alpha-chymotrypsin was not inhibited, suggesting that vanadate preferentially inhibits the amidolytic activity of trypsin and trypsin-like enzymes. These results show that vanadate prolongs the clotting time of plasma through mechanisms involving in part the inhibition of the activity of both factor Xa and thrombin.

Anticoagulant Action of Vanadate.