988-2 Thrombin Activity, but not Generation, is Inhibited by Intravenous Heparin Following Thrombolysis: Results from the GUSTO Hemostasis Substudy

Although thrombolytic therapy has been shown to improve survival in the setting of acute myocardial infarction, failure to reperfuse and reocclusion, both felt to be mediated in part by thrombin, continue to be significant problems. To study the impact of heparin on thrombin in thrombolytic treated patients, we evaluated hematologic parameters after administering streptokinase (SK) in GUSTO patients receiving either immediate IV heparin or delayed SQ heparin. Thrombin generation was estimated by assay for prothrombin fragment 1.2 (F1.2) and thrombin activity by fibrinopeptide A (FpA). 67 patients randomized to SK and IV heparin and 63 patients randomized to SK and SQ heparin were included. IV heparin was given as a 5000 U bolus followed by 1000–1200 units per hour adjusted to an aPTT of 60–85 seconds, and SQ heparin was given as 12,500 U twice daily beginning 4 hours after thrombolytic therapyFpA (ng/ml) and Fl.2 (ng/ml)leveis increased after starting thrombolytic therapy among patients treated with SQ heparin, in whom steady-state heparin levels do not occur for at least 24 hours. The FpA increase was inhibited with IV heparin. On the other hand, IV heparin did not inhibit the rise in F1.2 or significantly suppress it below baseline over the course of therapy.ConclusionIn the first 24 hours following thrombolytic therapy, IV heparin suppresses the increase in thrombin activity but not the increase in thrombin generation. Strategies to inhibit factors earlier in the cascade (i.e. Factors V, IX, and XI, by suppressing thrombin generation, may be an important goal for future management of acute coronary syndromes