THE ASSOCIATION OF ANTICOAGULANT PROTEIN CONCENTRATIONS WITH ACUTE MYOCARDIAL-INFARCTION IN THE THROMBOLYSIS IN MYOCARDIAL-INFARCTION PHASE-II (TIMI-II) TRIAL

Background: Little is known about the relationship between myocardial infarction and the coagulation inhibitors protein C, protein S, and an tithrombin III (ATIII). Methods: We explored the hypothesis that parti al deficiencies in protein C, protein S, and ATIII may be associated w ith acute myocardial infarction by comparing the baseline levels of th ese anti coagulants in a sample of participants in the Thrombolysis in Myocardial Infarction Phase II Trial (TIMI II) to the levels in a sam ple of Red Cross donors. We also examined the changes in concentration s of hemostatic and inhibitory factors tors during thrombolytic therap y, the correlations between the inhibitors and plasminogen and fibrino gen, and the asso ciation of baseline inhibitor levels with the degree of plasmin generation during treatment. Levels of protein C, free and to tal protein S, ATIII, fibrinogen, tissue type plasminogen activato r (t-PA), plasminogen, and alpha-2 antiplasmin were measured in plasma samples obtained at baseline before treatment with thrombolytic thera py and at 50 minutes, 5 hours, and 8 hours after the start of therapy (n = 92). Protein C, free and total protein S, and ATIII were also mea sured in plasma samples from comparable Red Cross donors (n = 92). Res ults: Baseline protein C and ATIII levels were higher in the TIMI II s ubjects than in controls (3.7 mu g/ml vs 3.3 for protein C, P = 0.002; 118% vs 111% for ATIII, P = 0.006). Free and total protein S levels w ere lower in the TIMI II subjects than in controls (4.3 mu g/ml vs 5.2 for free protein S, and 15.3 mu g/ml vs 17.2 for total protein S, P = 0.001). There were no major changes in protein C or protein S levels after initiation of thrombolytic therapy, but there was a 13% decrease in ATIII. Significant correlations were found between baseline protei n C, protein S, ATIII, and plasminogen; none of these factors were cor related with baseline fibrinogen concentration. The pretreatment level s of the inhibitors were correlated with markers of the amount of plas min generated during therapy. Conclusions: It is not likely that parti al protein C or ATIII deficiency is commonly associated with myocardia l in farction. It is more likely that at the time of infarction, these inhibitors are somewhat higher possibly due to a homeostatic response to previous plaque rupture and thrombosis. Partial protein S deficien cy may play a role in coronary thrombosis. The levels of these inhibit ors at the time of infarction may be important in the efficacy of thro mbolytic therapy.