Synergistic Effect of Antithrombin III. Activated Protein C and Heparin on the Inhibition of the Tissue Thromboplastin-Mediated Coagulation

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The synergistic effect of antithrombin III (ATIII), activated protein C (APC) and heparin on the tissue thromboplastin (TP)-mediated coagulation cascade was studied. APC prolonged the activated partial thromboplastin time of human plasma with increasing APC concentration but affected the prothrombin time only slightly. Neither ATIII nor heparin prolonged the prothrombin time by itself, while a mixture of APC and heparin strongly inhibited the coagulation. When the effects of APC, heparin and ATIII on the TP-mediated coagulation were examied with a solution consisting of prothrombin, factor V, factor VII, factor X and fibrinogen at physiological concentrations, the coagulation time was prolonged only slightly by the APC-heparin or ATIII-heparin mixture. However, the coagulation time was prolonged markedly by simultaneous addition of APC, ATIII and heparin to the solution. Inhibition of thrombin activity by the ATIII-APC-heparin mixture was weak as compared with that by the ATIII-heparin mixture after a 1-min incubation, but after a 2-min incubation the inhibitory activities were equal. Suppression of thrombin activity by the ATIII-APC-heparin mixture was supposed to be due to the inhibition of the interaction between ATIII and heparin on thrombin by APC because the APC-ATIII-heparin complex was detected by crossed immunoelectrophoresis but not by sodium dodecyl sulfate (SDS)-polyacrylamide electrophoresis. When the inhibitory effect of APC alne or the APC-heparin mixture on the platelet prothrombin converting activity (PPCA) was examined, heparin accelerated the PPCA inhibition by APC. These results suggested that the coexistence of APC, ATIII and heparin was essential in the modulation of the TP-mediated coagulation cascade and that the APC-ATIII-heparin, APC-heparin and ATIII-heparin complexes also play an important role in the modulation of the TP-mediaed coagulation cascade.
公益社団法人日本薬学会の論文
1989-03-25

Synergistic Effect of Antithrombin III. Activated Protein C and Heparin on the Inhibition of the Tissue Thromboplastin-Mediated Coagulation

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