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(Circulation. 1999;100:1858-1864.)
© 1999 American Heart Association, Inc.

Clinical Investigation and Reports

Platelet Function During and After Thrombolytic Therapy for Acute Myocardial Infarction With Reteplase, Alteplase, or Streptokinase

Martin Moser, MD; Thomas Nordt, MD; Karlheinz Peter, MD; Johannes Ruef, MD; Benedikt Kohler, MD; Marc Schmittner, BA; Richard Smalling, MD, PhD; Wolfgang Kübler, MD; Christoph Bode, MD

From Internal Medicine III (Cardiology), University of Heidelberg, Heidelberg, Germany (M.M., T.N., K.P., J.R., B.K., M.S., W.K., C.B.), and the University of Texas, Houston, Tex (R.S.).

Correspondence to Christoph Bode, MD, Internal Medicine III (Cardiology), University of Freiburg, Hugstetterstrasse 55, 79106 Freiburg, Germany.

Background—Changes in platelet aggregation (PA) and platelet surface receptor expression induced by thrombolytic therapy for acute myocardial infarction may influence the rate of initial reperfusion and early reocclusion.

Methods and Results—In the RAPID-1 (Reteplase Angiographic Phase II International Dose-finding study), RAPID-2 (Reteplase vs Alteplase Patency Investigation During myocardial infarction), INJECT (INternational Joint Efficacy Comparison of Thrombolytics), and GUSTO-3 (Global Use of Strategies To Open occluded coronary arteries) trials, 126 patients were enrolled in a single center. Patients were treated with either conventional alteplase (100 mg/180 min; n=15), accelerated alteplase (100 mg/90 min; n=21), reteplase 10+10-U double bolus (n=50), reteplase 10+5-U double bolus (n=15), reteplase 15-U single bolus (n=15), or streptokinase (1.5 MU/60 min; n=10). PA (after stimulation with ADP), P-selectin expression and fibrinogen binding to glycoprotein (GP) IIb/IIIa (determined by flow cytometry with and without stimulation with ADP), and levels of soluble P-selectin, prothrombin fragments F1 and F2, thrombin-antithrombin complexes (TAT), and antithrombin III (ATIII) were determined. PA decreased significantly at 1 and 2 hours in patients treated by 10+10-U reteplase or by streptokinase. Fibrinogen binding to platelet GP IIb/IIIa followed a similar pattern. Significant thrombin generation and significantly elevated thrombin levels during thrombolysis were reflected by increased F1 and F2 fragments and TAT levels in all treatment groups. ATIII levels decreased significantly during thrombolytic therapy.

Conclusions—A decrease in PA in patients treated by reteplase or streptokinase compared with alteplase could be observed in the early phase. Double bolus (10+10 U) reteplase and streptokinase resulted in lower PA at 1 and 2 hours than therapy with accelerated alteplase. Total fibrinogen and fibrinogen binding to GP IIb/IIIa tended to be lower during the first 2 hours after reteplase than after accelerated alteplase.

Key Words: thrombolysis • platelet aggregation inhibitors • plasminogen activators • myocardial infarction • reperfusion

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