The effect of high-concentrate thrombin on coagulation and fibrinolysis.

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Since high-concentrate thrombin preparations have excellent effectiveness for local hemostasis in patients with coagulopathies, the blood coagulation mechanism in the presence of high-concentrate thrombin, using purified thrombin and plasminogen-free fibrinogen was investigated. 1) The blood coagulation analyzer, Coag-Stat was utilized in the kinetic study of fibrinogen to fibrin transformation.The initial velocity of fibrin formation was accelerated as the concentration increased and the amounts of fibrin were gradually decreased in relation to the given amount of sodium heparin.The general result of this investigation was that anti-thrombin III and a large amount of heparin caused neutralization of dosage of 100 units/ml thrombin with neutralization increasing with heparin dosage. 2) The influence of coagulum stiffness, which depended on the thrombin dose, was investigated by thrombelastograph.The higher concentration thrombin solutions above 10 units/ml dosage had indicated a fibrinolytic activity by reason of "ma" value decrease.This was particularly remarkable with dosages of 100 units/ml and 1, 000 units/ml thrombin. 3) The progress of the digestion of fibrin by high-concentrate thrombin was also monitored by SDS-polyacrylamide gel electrophoresis of the lysed fibrin at frequent intervals during the 180 minute digestion period.The gels stained with Coomassie blue, which were applied to plasminogen-free fibrinogen, showed the α, β and γ chains. After 60, 120 and 180 min of digestion the α chains were present in much smaller amounts and appear to have been extensively degraded. 4) From the standpoint of prophylactic and continual effectiveness in postoperative bleeding, we also examined the diffusion state of high-concentrate thrombin from the fibrin network. In the investigation of thrombin diffusion, high-concentration thrombin was diffused on an agarose plate, containing plasminogen-free fibrinogen, and was seen to precipitate an increasing amount of fibrin. From the result of these study, the accelerative function of thrombin in blood coagulation was again confirmed.High-concentrate thrombin penetrated and diffused into the fibrin network during a period of several hours.We presume that this function produces continual hemostatic efficacy.In a practical clinical application of thrombin, it seems that the plasma inhibitor and released heparinoid affect the preparation.From this experiment about 100 units/ml of thrombin were neutralized under AT-III and extra doses of heparin.Moreover, taking many kinds of plasma inhibitors into consideration, this approach showed that clinically more than 1, 000 units/ml thrombin was more effective.
社団法人日本口腔外科学会の論文

The effect of high-concentrate thrombin on coagulation and fibrinolysis.

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