An Antithrombin Reaction Related to Prothrombin Activation

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Abstract
Current nomenclature is inadequate to refer conveniently to the several antithrombic activities of plasma. It is proposed that the terms antithrombin I, antithrombin II, anti-thrombin III, and antithrombin IV be used, as follows: adsorption of thrombin or fibrin: antithrombin I; the plasma cofactor of heparin: antithrombin II; the plasma factor which neutralizes thrombin and is destroyed by ether: antithrombin III; and the material of ether-treated plasma which acts in relationship with prothrombin activation: antithrombin IV. In a thrombin titer method of analysis, plasma is defibrinated, and antithrombin III activity is removed with ether. Prothrombin is then reacted with Ca and thromboplastin as in a 1-stage prothrombin time analysis. Samples are taken repeatedly from the reaction mixture and added to fibrinogen to obtain an indication of thrombin concn. From the series of clotting times one observes the accumulation of thrombin activity and its subsequent disappearance. The thrombin titer method was used to study antithrombin IV. Antithrombin IV is found in dog plasma and in plasma after adsorption on BaCO3. Some is also found in dog serum. Large amts. of a platelet-AcG preparation, large amts. of materal adsorbed from bovine serum and eluted therefrom and crude bovine prothrombin prepns. tend to inhibit antithrombin IV activity. BaCO3 removes material from dog plasma which is concerned with the activation of prothrombin and that material is not found in appreciable quantities, if at all, in purified prothrombin prepns. of high specific activity.