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Effect of tenecteplase versus alteplase on platelets during the first 3 hours of treatment for acute myocardial infarction: the Assessment of the Safety and Efficacy of a New Thrombolytic Agent (ASSENT-2) platelet substudy.

Publication ,  Journal Article
Serebruany, VL; Malinin, AI; Callahan, KP; Binbrek, A; Van De Werf, F; Alexander, JH; Granger, CB; Gurbel, PA ...
Published in: Am Heart J
April 2003

BACKGROUND: Platelets play a pivotal role in the pathogenesis of acute myocardial infarction, as well as in the occurrence of coronary artery reocclusion and bleeding events. Therefore, the success of fibrinolytic therapy may be dependent on its direct effects on platelets. METHODS AND RESULTS: We sought to determine how tenecteplase (TNK) and alteplase (tPA) affect platelets in vitro in human volunteers and ex vivo by use of patient data from the Assessment of the Safety and Efficacy of a New Thrombolytic Agent (ASSENT-2) trial. For the in vitro studies, whole blood from 9 healthy volunteers was incubated with 30 mg TNK and 60 mg tPA. Platelet function was measured by conventional aggregometry, bedside point-of-care devices, and sensitive flow cytometry techniques. For the ex vivo study, 41 patients were selected from the ASSENT-2 trial: 21 had received TNK and 20 had received tPA. Each patient underwent 7 serial blood draws every 30 minutes for 3 hours. Levels of platelet endothelial cell adhesion molecule-1 (PECAM-1), vascular cell adhesion molecule-1 (VCAM-1), P-selectin, beta-thromboglobulin, platelet factor 4, thromboxane, and prostacyclin were measured by enzyme-linked immunosorbent assay. Significant inhibition of conventional and whole blood aggregation and reduced platelet function by point-of-care analyzers were observed for both agents, but mostly in the TNK-treated samples. After incubation with TNK, flow cytometry revealed decreased expression of glycoprotein IIb/IIIa, PECAM-1, vitronectin receptor, CD151, and formation of the platelet-monocyte aggregates. Serial samples from patients in the ASSENT-2 trial showed a significant decrease of soluble platelet-endothelial biomarkers in the TNK group. There was a trend toward decreased platelet function characteristics with tPA; however, these differences were much smaller than those observed with TNK. CONCLUSIONS: Both tPA and TNK were shown to affect platelet function in human volunteers and in patients with AMI early after thrombolysis. The antiplatelet properties of TNK were shown to be more profound than those of tPA. These findings are relevant to ongoing investigations of combination therapy with fibrinolytic and antiplatelet agents in patients with AMI.

Duke Scholars

Published In

Am Heart J

DOI

EISSN

1097-6744

Publication Date

April 2003

Volume

145

Issue

4

Start / End Page

636 / 642

Location

United States

Related Subject Headings

  • Tissue Plasminogen Activator
  • Time Factors
  • Thrombolytic Therapy
  • Tenecteplase
  • Platelet Aggregation
  • Myocardial Infarction
  • Middle Aged
  • Male
  • In Vitro Techniques
  • Humans
 

Citation

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Serebruany, V. L., Malinin, A. I., Callahan, K. P., Binbrek, A., Van De Werf, F., Alexander, J. H., … Assessment of the Safety and Efficacy of a New Thrombolytic Agent platelet substudy, . (2003). Effect of tenecteplase versus alteplase on platelets during the first 3 hours of treatment for acute myocardial infarction: the Assessment of the Safety and Efficacy of a New Thrombolytic Agent (ASSENT-2) platelet substudy. Am Heart J, 145(4), 636–642. https://doi.org/10.1067/mhj.2003.210
Serebruany, Victor L., Alex I. Malinin, Kevin P. Callahan, Azan Binbrek, Frans Van De Werf, John H. Alexander, Christopher B. Granger, Paul A. Gurbel, and Paul A. Assessment of the Safety and Efficacy of a New Thrombolytic Agent platelet substudy. “Effect of tenecteplase versus alteplase on platelets during the first 3 hours of treatment for acute myocardial infarction: the Assessment of the Safety and Efficacy of a New Thrombolytic Agent (ASSENT-2) platelet substudy.Am Heart J 145, no. 4 (April 2003): 636–42. https://doi.org/10.1067/mhj.2003.210.
Serebruany VL, Malinin AI, Callahan KP, Binbrek A, Van De Werf F, Alexander JH, Granger CB, Gurbel PA, Assessment of the Safety and Efficacy of a New Thrombolytic Agent platelet substudy. Effect of tenecteplase versus alteplase on platelets during the first 3 hours of treatment for acute myocardial infarction: the Assessment of the Safety and Efficacy of a New Thrombolytic Agent (ASSENT-2) platelet substudy. Am Heart J. 2003 Apr;145(4):636–642.
Journal cover image

Published In

Am Heart J

DOI

EISSN

1097-6744

Publication Date

April 2003

Volume

145

Issue

4

Start / End Page

636 / 642

Location

United States

Related Subject Headings

  • Tissue Plasminogen Activator
  • Time Factors
  • Thrombolytic Therapy
  • Tenecteplase
  • Platelet Aggregation
  • Myocardial Infarction
  • Middle Aged
  • Male
  • In Vitro Techniques
  • Humans