血栓の形成機序

Abstract

Mechanism of thrombus formation related to blood procoagulants and their inhibitors in blood was studied. In vitro experiments revealed that amount of thrombin adsorbed to fibrin during blood coagulation process was about 35% of thrombin which was neutralized by normal defibrinated plasma in 5 minutes at 37°C and that about 60% of thrombin inhibiting capacity of defibrinated plasma in this condition was attributed to antithrombin III. Effects of changes of concentrations of procoagulants and/or thrombin inhibitors in plasma on intrinsic blood clotting system were investigated by measuring activated partial thromboplastin times (APTT) of mixtures of 0.1ml of normal plasma and 0.1ml of buffered saline, normal plasma, BaSO4 adsorbed plasma, heated (56°C, 2 minutes) plasma, bentonite adsorbed plasma or fraction of fibrinogen obtained from human plasma. Results were as follows:1) APTT of mixture of normal plasma and buffered saline was 28.6 seconds; 2) 0.2ml of normal plasma (concentrations of all procoagulants and antithrombins were doubled), 34.6 seconds; 3) mixture of normal plasma and BaSO4 adsorbate (did not contain factors VII, IX, X and II, however the other procoagulants and inhibitors remained), 38.8 seconds; 4) mixtures of normal plasma and heated plasma (fibrinogen was eliminated and factor V activity was halved, although the other procoagulants and inhibitors were unaffected), 40.7 seconds; 5) mixture of normal plasma and bentonite plasma (only α2-macroglobulin and α1-antitrypsin unchanged. α2-plasmin inhibitor halved. The other procoagulants and inhibitors were removed), 28.6 seconds; 6) addition of fibrinogen solution to normal plasma; 38.2 seconds. In cases of acute myocardial infarction, levels of factor VIII, V and fibirnogen increased and concentrations of antithrombin III decreased, while levels of prekallikrein, which is a kind of procoagulants, and of factor X unchanged. In healthy subjects or cases of acute myocardial infarction, statistically significant positive correlations between factor X activities and antithrombin III levels in plasma were observed. However ratio of antithrombin III to factor X activity was usually lower in the patients with acute myocardial infarction. In many cases in whom thromboembolic complications developed, levels of antithrombin III decreased frequently. From these results, it is stressed that inhibitors of activated blood procoagulants is more important than blood clotting factors in thrombus formation, probably because process of blood coagulation is amplified by repetition of activation (proteolysis) of procoagulants (zymogen) by activated clotting factors (enzyme). Among cases of arteriosclerotic diseases, hypercoagulable state was observed in patients with acute myocardial infarction.