Autoprothrombin C in Irregular Blood Clotting

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Abstract
In this study autoprothrombin C was considered in relationship to the hemorrhagic diseases. Concentrates of autoprothrombin C were made from purified prothrombin known to be homogeneous by several criteria. These autoprothrombin C preparations were free of thrombin, and were almost a single component when analyzed by centrifugation. Autoprothrombin C corrected the partial thromboplastin time and produced prothrombin consumption in all the plasmas obtained from patients with hemorrhagic diseases except parahemophilia. In the case of hemophilia B prothrombin consumption was obtained with the addition of purified prothrombin or purified autoprothrombin II. In the case of Stuart plasma prothrombin consumption was rapid after the addition of purified prothrombin or purified prothrombin chromatographed on Amberlite ICR-50, but not after the addition of purified prothrombin that was chromatographed on DEAE cellulose. The latter prothrombin is an abnormal prothrombin molecule and does not readily yield autoprothrombin C. It is concluded that Stuart prothrombin is abnormal and that this is a molecular disease. There is no need to postulate the existence of factor X to account for the irregular prothrombin activation in Stuart plasma. The most important question considered was how can autoprothrombin C be generated from prothrombin to promote the autocatalytic activation of prothrombin. Certain prothrombin molecules do not yield this enzyme, but normal prothrombin does. However, it does so only under certain conditions of activation. By applying the new knowledge of prothrombin chemistry to blood clotting irregularities in hemorrhagic diseases the following main considerations highlight the common deviations: 1. Abnormal prothrombin molecule, 2. Changes related to the derivatives of prothrombin, 3. Accessories needed for the generation of autoprothrombin C so it can function in auto-catalysis are irregular, and 4. Accessories needed for the function of autoprothrombin C after it is out of the prothrombin molecule are irregular. In the first group is Stuart Plasma. In the second group falls hemophilia B (autoprothrombin II) and the so-called factor VII deficiency (autoprothrombin I). In the third group is hemophilia A. In the fourth group is parahemophilia, and the platelet abnormalities. * This investigation was supported by a research grant H-5141 from the National Heart Institute, National Institutes of Health, U.S. Public Health Service. ** Rockefeller Foundation Research Fellow.