PROTHROMBIN CONSUMPTION, SERUM PROTHROMBIC ACTIVITY AND PROTHROMBIN CONVERSION ACCELERATOR IN HEMOPHILIA AND THROMBOCYTOPENIA 12

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Abstract
Studies are presented on the clotting defect in hemophilia and thrombocytopenia with reference to prothrombin consumption and serum prothrombic activity. Prothrombic activity was detd. by the 1-stage procedure in which fresh prothrombin-free (BaSO4 adsorbed) normal plasma is used as diluent. Detns. were also made by the modified 2-stage procedure of Ware and Seegers in which accelerator globulin is provided by bovine serum. Serum prothrombin conversion accelerator (spca) was measured by the accelerating effect of serum of fractions thereof on the prothrombin time of a mixture of normal plasma and prothrombin-free (BaSO4) normal plasma. Sera from hemophilic, thrombocytopenic and silicone blood show abnormally large amts. of 1-stage prothrombic activity, frequently exceeding that of the parent plasmas. By the 2-stage procedure, prothrombic activity is lower but still is greater than normal. A prothrombin conversion accelerator (spca) can be separated from the sera. The high 1-stage prothrombic activity reflects unconsumed prothrombin plus spca which evolves during coagulation. The clotting of hemophilic and silicone blood was accelerated by the addition of purified spca. In hemophilia the 1-stage serum prothrombic activity was not reduced, but by the 2-stage technique substantial prothrombin consumption was demonstrable. The high prothrombic activity of the serum from one patient with idiopathic thrombocytopenic pur-pur a, reflecting a definite coagulation defect, disappeared with clinical improvement following splenectomy. The demonstration of a prothrombin conversion accelerator which evolves as a consequence of the transition from plasma to serum raises serious doubt as to the validity of computing actual serum prothrombin content and prothrombin consumption during coagulation from observations of the serum prothrombic activity as detd. by the 1-stage procedure since the prothrombic activity reflects both unconsumed prothrombin and the serum prothrombin conversion accelerator which has evolved. It is accordingly concluded that the 2-stage procedure for measuring prothrombin provides a more reliable measure of serum prothrombin in the 1-stage technique.