The nature of plasma antithrombin activity.

In plasma antithrombin studies it is essential to recognize two separate effects on thrombin. One is concerned with thrombin disposal, and the magnitude of this effect is determined by finding how much thrombin remains after the antithrombin reaction has gone to completion. The other effect is concerned with interference with the thrombin-fibrinogen reaction, there being no thrombin activity destroyed by this mechanism. In the disposal of thrombin, plasma antithrombin is not influenced by heparin. The amount of thrombin destroyed is constant for a given amount of defibrinated plasma and is independent of the initial thrombin concentration, provided the initial quantity of thrombin is above the antithrombin capacity of the plasma. For bovine plasma, the antithrombin capacity is about 710 units of thrombin. In contrast, if the initial quantity of thrombin is less that the antithrombic capacity of the plasma, some thrombin may remain after equilibrium conditions have been reached. In addition to plasma antithrombin, fibrin may remove certain quantities of thrombin activity from solution by adsorption. Heparin increases the amount of thrombin adsorbed on fibrin whereas albumin decreases the amount of thrombin adsorbed. The adsorbed thrombin can be recovered by lysis of the fibrin with fibrinolysin. The general concept that heparin has an antithrombic effect in conjunction with a plasma cofactor is explained on the basis that this mechanism interferes in the thrombin-fibrinogen reaction. No thrombin is destroyed by this mechanism.