抄録
Previous studies showed an early increase in concentrations of thrombin-antithrombin III complex (TAT) and fibinopeptide A (FPA) during thrombolytic therapy; but the mechanism of activation of coagulation with fibrinolysis is not known. The aim of this study is to clarify the mechanism of activation of coagulation with tissue-type plasminogen activator (t-PA) in vitro. Prothrombin fragment 1+2 (F1+2), TAT and FPA levels significantly increased in anticoagulated normal plasma after incubation with t-PA (1×103U/ml and 1×104U/ml) compared without t-PA and the increas of these marker levels was dose dependent. By incubation of normal plasma and coagulation factor deficient plasma (factor V, VII, IX, X deficient plasma) with t-PA (1×103U/ml), generations of F1+2 and FPA significantly decreased in factor V, VII and X deficient plasma compared to standard plasma, however the amount of F1+2 and FPA generated in factor IX deficient plasma was comparable with normal. F1+2 immunoreactivity also increased in normal plasma after incubation with plasmin. By incubation of purified prothrombin (physiological concentration) with t-PA and plasmin, no generations of F1+2 were observed with t-PA, but one tenth levels of generations of F1+2 observed with plasmin compared to addition of plasmin to normal plasma.
These results demonstrated not only an activation of prothrombin but also an activation of extrinsic pathway (in part via factor VII) associated with stimulation of fibrinolysis.
