Increased fibrin specificity and reduced paradoxical thrombin activation of the combined thrombolytic regimen with reteplase and abciximab versus standard reteplase thrombolysis

Drugs Exp Clin Res. 2004;30(2):47-54.

Abstract

In patients with acute myocardial infarction treated with thrombolytics, platelet activation as well as alterations of the hemostatic and fibrinolytic systems have been described favoring early infarct-related artery reocclusion. We investigated the effects of a newer thrombolytic regimen with half-dose double-bolus reteplase (2 x 5 IU, 20 patients) combined with abciximab versus full-dose reteplase (2 x 10 IU, 18 patients) on the fibrinolytic and the hemostatic system in patients with acute ST-segment elevation (in the electrocardiogram) myocardial infarction. The thrombolytic regimen with half-dose reteplase in combination with abciximab caused in vivo a lower systemic plasminemia and a lower paradoxical activation of the contact phase of the coagulation system (measured as activated factor XII); a lower paradoxical thrombin activation/generation; and a lesser extent of fibrinogen breakdown compared with the reteplase regimen. These results could be, at least in part, a possible explanation for the observed significantly lower rates of reinfarction until 7 days after enrollment and of recurrent ischemia in the combination group in the Global Use of Strategies to Open Occluded Coronary Arteries V (GUSTO V) trial.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Abciximab
  • Aged
  • Antibodies, Monoclonal / therapeutic use*
  • Anticoagulants / therapeutic use*
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Female
  • Fibrinolytic Agents / administration & dosage
  • Fibrinolytic Agents / therapeutic use*
  • Humans
  • Immunoglobulin Fab Fragments / therapeutic use*
  • Male
  • Middle Aged
  • Myocardial Infarction / drug therapy*
  • Platelet Aggregation / drug effects
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / therapeutic use*
  • Tissue Plasminogen Activator / administration & dosage
  • Tissue Plasminogen Activator / therapeutic use*

Substances

  • Antibodies, Monoclonal
  • Anticoagulants
  • Fibrinolytic Agents
  • Immunoglobulin Fab Fragments
  • Recombinant Proteins
  • reteplase
  • Tissue Plasminogen Activator
  • Abciximab