Differential antiplatelet effects of various glycoprotein IIb-IIIa antagonists

Timm Dickfeld, Andreas Ruf, Gisela Pogatsa-Murray, Iris Muller, Bernd Engelmann, Winfried Taubitz, Jorg Fischer, Oliver Meier, Meinrad Gawaz

Research output: Contribution to journalArticle

Abstract

The blockade of platelet glycoprotein IIb-IIIa (GPIIb-IIIa) was recently introduced as a new antiplatelet strategy. At present, various GPIIb-IIIa inhibitors are available to treat patients with acute coronary syndrome or when undergoing percutaneous coronary interventions. The current study systematically evaluates the antiplatelet effects of GPIIb-IIIa inhibitors in clinical use. Using conformation-dependent monoclonal antibodies [ligand-induced binding sites (LIBS-1), PMI-1] and flow cytometry, we showed that the GPIIb-IIIa antagonists abciximab, integrelin, lamifiban, and tirofiban, but not EMD 122347 or YM 337, induced LIBS activity of platelet GPIIb-IIIa. The LIBS activity of GPIIb-IIIa antagonists correlates with a proaggregatory response of fixed platelets pretreated with GPIIb-IIIa antagonists (intrinsic activity). All tested GPIIb-IIIa antagonists completely inhibit concentration-dependent ADP (20 μmol/l)-induced aggregation. In contrast, substantial TRAP (25 μmol/l)-induced platelet aggregation still occurs even at high inhibitor concentrations of the tested GPIIb-IIIa antagonists. In addition, we show that GPIIb-IIIa antagonists are poor inhibitors of platelet release reaction (ATP and P-selectin secretion) especially when strong agonists such as TRAP are used to activate platelets. Inhibition of platelet procoagulant activity (thrombin generation) by GPIIb-IIIa antagonists is dependent on the type and concentration of antagonists and on the strength of stimulus (thrombin, tissue factor) used to induce platelet-dependent thrombin generation. The present data show that significant pharmacological differences exist between GPIIb-IIIa antagonists that may have consequences for antithrombotic strategies and for future drug development.

Original languageEnglish (US)
Pages (from-to)53-64
Number of pages12
JournalThrombosis Research
Volume101
Issue number2
DOIs
StatePublished - Jan 15 2001
Externally publishedYes

Fingerprint

Platelet Glycoprotein GPIIb-IIIa Complex
Blood Platelets
Thrombin
tirofiban
Integrin beta3
P-Selectin
Platelet Aggregation Inhibitors
Thromboplastin
Percutaneous Coronary Intervention
Acute Coronary Syndrome
Platelet Aggregation
Adenosine Diphosphate
Flow Cytometry
Adenosine Triphosphate
Binding Sites
Monoclonal Antibodies
Pharmacology
Ligands
Pharmaceutical Preparations

Keywords

  • Aggregation
  • GPIIb-IIIa inhibitors
  • Intrinsic activity
  • LIBS induction
  • Platelets
  • Procoagulant activity

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Hematology

Cite this

Dickfeld, T., Ruf, A., Pogatsa-Murray, G., Muller, I., Engelmann, B., Taubitz, W., ... Gawaz, M. (2001). Differential antiplatelet effects of various glycoprotein IIb-IIIa antagonists. Thrombosis Research, 101(2), 53-64. https://doi.org/10.1016/S0049-3848(00)00385-6

Differential antiplatelet effects of various glycoprotein IIb-IIIa antagonists. / Dickfeld, Timm; Ruf, Andreas; Pogatsa-Murray, Gisela; Muller, Iris; Engelmann, Bernd; Taubitz, Winfried; Fischer, Jorg; Meier, Oliver; Gawaz, Meinrad.

In: Thrombosis Research, Vol. 101, No. 2, 15.01.2001, p. 53-64.

Research output: Contribution to journalArticle

Dickfeld, T, Ruf, A, Pogatsa-Murray, G, Muller, I, Engelmann, B, Taubitz, W, Fischer, J, Meier, O & Gawaz, M 2001, 'Differential antiplatelet effects of various glycoprotein IIb-IIIa antagonists', Thrombosis Research, vol. 101, no. 2, pp. 53-64. https://doi.org/10.1016/S0049-3848(00)00385-6
Dickfeld T, Ruf A, Pogatsa-Murray G, Muller I, Engelmann B, Taubitz W et al. Differential antiplatelet effects of various glycoprotein IIb-IIIa antagonists. Thrombosis Research. 2001 Jan 15;101(2):53-64. https://doi.org/10.1016/S0049-3848(00)00385-6
Dickfeld, Timm ; Ruf, Andreas ; Pogatsa-Murray, Gisela ; Muller, Iris ; Engelmann, Bernd ; Taubitz, Winfried ; Fischer, Jorg ; Meier, Oliver ; Gawaz, Meinrad. / Differential antiplatelet effects of various glycoprotein IIb-IIIa antagonists. In: Thrombosis Research. 2001 ; Vol. 101, No. 2. pp. 53-64.
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