1. Data are presented which demonstrate that progressive antithrombin activity results from the interaction of three factors: antithrombin, an antithrombin inhibitor, and a platelet factor. In plasma, the antithrombin is held inactive by combination with inhibitor so that no free antithrombic activity is present. When platelets are disrupted—namely, in clotting—the platelet factor made available binds the inhibitor, releasing antithrombin to react with thrombin.

2. Antithrombin was isolated from plasma in the 70-75 per cent ammonium sulfate fraction. It was relatively heat stable at 56-57 C. for 5 minutes and was not soluble in perchloric acid.

3. Inhibitor was isolated from plasma in the 30-50 per cent ammonium sulfate fraction. It was inactivated at 56-57 C. for 5 minutes. It was soluble in perchloric acid in which it was purified by a factor of 300.

4. Platelet factor was present in the sedimentable fragments of platelets.

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