HEPARIN AND NATURAL ANTIPROTHROMBIN IN RELATION TO ACTIVATION AND "ASSAY" OF PROTHROMBIN

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Abstract
A quantitative study of clotting-times with thrombin and prothrombin (maximally activated with Ca and thrombo-plastin) shows that the prothrombin dilutions give more than the theoretical yield of thrombin. The thromboplastin variable is ruled out, as it is optimal in all cases. Under these circumstances, thromboplastin variations merely affect the rate of thrombin formation and the optimum clotting-time is a measure of the thrombin yield. The addition of a fixed amt. of heparin slows the rate of prothrombin activation and may result in a lessened amt. (effectiveness) of the thrombin formed. The 1st action is anti-thromboplastic, interpreted as an inhibition of the tryptase-like thromboplastic enzyme. The 2d effect is truly anti-prothrombic, due to an action of prothrombin protein itself. These 2 phenomena comprise the "antiprothrombic" (1st phase inhibiting) actions of heparin and are easily separable, by control expts., from the 2d phase inhibitions, (a) progressive and (b) immediate. An immediate anti-thrombin is formed by heparin plus a plasma co-factor (proantithrombin). A similar, but independently acting, co-factor for the first phase is demonstrated in crude plasma "albumin." It markedly potentiates the antiprothrombic actions of heparin.

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