Thrombolysis, With or Without Heparin, During the First Nine Weeks After Acute Myocardiat Infarction

Abstract

The duration and characteristics of fibrinolytic "shut-down" were studied in 40 patients serially for a 9-week period after acute myocardial infarction (AMI). Patients were randomized into four equal groups to receive streptokinase (SK), SK plus heparin (SK + H), recombinant tissue plasminogen activator (rt-PA) or recombinant t-PA plus heparin (rt-PA + H). All patients received oral aspirin. Plasma fibrinolysis was assessed by performance of the following tests: fibrin plate lysis (FPL), tissue plas. minogen activator (t-PA) activity and t-PA antigen (Ag), plasminogen (plg) and α2-antiplasmin (α2-AP) activity, Clauss fibrinogen, and D-dimer. Prethrombolysis global fibrinolysis was normal in most patients, although plasminogen activator inhibitor (PAI) activity and PA inhibitor-1 antigen (PAI-I Ag) were increased 37.5% of the patients. Fibrin plate lysis was significantly decreased for the first 48 h in all four groups (p < 0.05-0.002) compared with normal controls (n = 10); the decrease persisted longest (5 days) in the group receiving rt-PA alone. The decreased fibrin plate lysis was accompanied by significantly increased D-dimer levels (p < 0.003-0.0002) as well as decreased plg and α2-AP activities (p < 0.05-0.0002), which persisted longer. (≤72 h) in patients receiving SK, indicating a more widespread activation of fibrinolysis in this group. Fibrinogen levels showed a rebound increase which began ≤24 h after thrombolysis while levels of plg and a2-AP were at their lowest. The fibrinogen rebound persisted for at least 6 weeks (p < 0.05-0.002). t-PA activity remained unchanged, and t-PA Ag levels were variable and showed no consistent pattern over the study period. PAI-1 Ag and PAI activity levels were significantly increased (p < 0.02-0.0005) in all four groups for the first 24 h, and individual patients showed increased levels at various times over the study period. The only significant prethrombolysis fibrinolytic change was increased PAI activity and PAI-1 Ag. The only significant effect of heparin was a shortening of the period of decreased global fibrinolysis observed in the rt-PA group from 5 to 2 days. Our findings show that the fibrinolytic shut-down after AMI in patients receiving thrombolysis is short-lived, lasting only a few days. Key Words : Thrombolysis—Myocardial infarction-Fibrinolysis-Heparin.