TISSUE THROMBOPLASTIN INDUCES RAPID INHIBITION OF FIBRINOLYSIS IN RABBITS

We studied the fibrinolytic enzyme system in non-pregnant female New Z ealand rabbits infused with rabbit brain tissue thromboplastin for 2 h and in rabbits receiving infusion of isotonic saline. The rabbits tre ated with thromboplastin responded with statistically significant chan ges in haemodynamic variables, a decrease in plasma concentration of f ibrinogen (P<0.01), a decrease in platelet concentration (P<0.01), a p rolongation in prothrombin time and activated partial thromboplastin t ime (APTT) (P<0.01), consistent with an induced intravascular coagulat ion. The thromboplastin infused animals had furthermore changes consis tent with activation and subsequent inhibition of the fibrinolytic enz yme system. The plasminogen activity dropped continuously during the 2 -h infusion (P<0.01) along with the activity of cc,antiplasmin (P<0.05 ). The activity of the urokinase-like plasminogen activator decreased slightly (P<0.05) during the 2-h infusion, while the factor XII-depend ent plasminogen activator activity did not change. The tissue-type pla sminogen activator activity decreased (P<0.01), and that of plasminoge n activator inhibitor 1 (PAI-1) increased pronouncedly after 1 hour of thromboplastin infusion (P<0.01). We conclude that infusion of tissue thromboplastin causes activation of both coagulation and fibrinolysis and that tissue thromboplastin mediates a rapid inhibition of t-PA wh ich is probably related to activation of platelets and release of PAI- 1.