Serial changes in hemostatic and fibrinolytic states induced by coronary thrombolytic therapy

The effects of coronary thrombolytic therapy with urokinase on the intrinsic hemostatic and fibrinolytic states were investigated by determining several markers for hemostatic and fibrinolytic activities in 6 patients with acute myocardial infarction who underwent coronary thrombolysis with urokinase. The markers for hemostasis and fibrinolysis were: markers for plasmin generation [α2-plasmin inhibitor (α2-PI), plasminogen, plasmin α2-PI complex (PIC)]; markers for fibrinolysis [fibrin/fibrinogen degradation products E fragment (FDP-E), FDP D-D dimer (D dimer), fibrinogen]; markers for hemostatic activity (prothrombin time (PT), antithrombin III (AT-III), protein C); markers for thrombin generation [thrombin antithrombin III complex (TAT)]; markers for intrinsic fibrinolytic activity [tissue plasminogen activator plasminogen activator inhibitor complex (TPA PAI complex)]. These markers were measured before, at 1 to 2 hours intervals during first 6 hours, daily during the next 3 days, and subsequently on the 7th and the 14th day after urokinase therapy. Fibrinolysis (determined by increased D dimer) occurred only when α2-PI became unmeasurable with 96 x 10⁴ or more units of urokinase administration, then persisted for more than 2 hours. TAT increased from 13.1 ± 15.4 to 70.8 ± 65.8 ng/ml soon after fibrinolysis occurred, indicating that thrombin generation occurred at the same time as fibrinolysis. The TPA PAI complex level before urokinase administration (26.4 ± 6.4 ng/ml) was greater than the normal upper limit, indicating increased intrinsic fibrinolytic activity, then decreased after urokinase administration. These findings suggested that urokinase administration might affect the intrinsic fibrinolytic activity. Our present results indicate that coronary thrombolytic therapy with urokinase operates as an extrinsic fibrinolytic agent and affects the intrinsic hemostatic and fibrinolytic states.