Effects of reteplase and alteplase on platelet aggregation and major receptor expression during the first 24 hours of acute myocardial infarction treatment. GUSTO-III Investigators. Global Use of Strategies to Open Occluded Coronary Arteries

J Am Coll Cardiol. 1998 Jun;31(7):1466-73. doi: 10.1016/s0735-1097(98)00172-7.

Abstract

Objectives: We sought to compare platelet characteristics after reteplase and alteplase therapy in the setting of the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO)-III trial.

Background: Platelet function may be impaired during thrombolysis in patients with an acute myocardial infarction. The effects of reteplase and alteplase on platelet aggregation and major surface antigen expression during the first 24 h of infarction therapy are unknown.

Methods: Platelet aggregation and receptor expression by flow cytometry were determined in 23 patients before thrombolysis and thereafter at 3, 6, 12 and 24 h.

Results: Aggregation was higher after reteplase at 24 h when induced by 5 micromol/liter adenosine diphosphate (ADP) (p = 0.007), 10 micromol/liter ADP (p = 0.02), collagen (p = 0.003) and thrombin (p = 0.009) than after alteplase. Reteplase therapy exhibited greater glycoprotein (GP) IIb/IIIa (p = 0.04), very late antigen-2 (p = 0.04) and platelet/endothelial cell adhesion molecule-I (p = 0.002) expression at 24 h. Trends toward decreased receptor expression early (3 to 6 h), followed by a progressive increase at 12 h and especially at 24 h occurred after both agents.

Conclusions: In this prospective clinical ex vivo platelet study, similar patterns of platelet aggregation and surface receptor expression occurred during the first 24 h of coronary thrombolysis with reteplase and alteplase. However, after reteplase, indicators of platelet activity were higher at 24 h after thrombolysis than after alteplase. These data suggest that GP IIb/IIIa inhibitors or other antiplatelet strategies may be particularly advantageous when used 12 to 24 h after thrombolysis, especially after reteplase therapy. It is at this time point during the first day of coronary thrombolysis that GP IIb/IIIa is markedly expressed and platelets are most active.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, Surface*
  • Blood Platelets / drug effects
  • Blood Platelets / immunology*
  • Female
  • Fibrinolytic Agents / pharmacology*
  • Fibrinolytic Agents / therapeutic use
  • Flow Cytometry
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / blood
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / physiopathology
  • Plasminogen Activators / pharmacology*
  • Plasminogen Activators / therapeutic use
  • Platelet Aggregation / drug effects*
  • Prospective Studies
  • Randomized Controlled Trials as Topic
  • Recombinant Proteins / pharmacology
  • Recombinant Proteins / therapeutic use
  • Statistics, Nonparametric
  • Thrombolytic Therapy*
  • Tissue Plasminogen Activator / pharmacology*
  • Tissue Plasminogen Activator / therapeutic use

Substances

  • Antigens, Surface
  • Fibrinolytic Agents
  • Recombinant Proteins
  • reteplase
  • Plasminogen Activators
  • Tissue Plasminogen Activator