Protease activated receptor-1 (PAR-1) mediated platelet aggregation is dependant on clopidogrel response

Rolf P. Kreutz, Jeffrey A. Breall, Yvonne Kreutz, Janelle Owens, Deshun Lu, Islam Bolad, Elisabeth Von Der Lohe, Anjan Sinha, David A. Flockhart

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Introduction: Clopidogrel inhibits ADP mediated platelet aggregation through inhibition of the P2Y12 receptor by its active metabolite. Thrombin induces platelet aggregation by binding to protease activated receptor-1 (PAR-1), and inhibition of PAR-1 has been evaluated in patients treated with clopidogrel to reduce ischemic events after acute coronary syndromes. Residual PAR-1 mediated platelet aggregation may be dependent on extent of clopidogrel response. Material and Methods: Platelet aggregation was measured in 55 patients undergoing elective PCI at 16-24 hours after 600 mg clopidogrel loading dose by light transmittance aggregometry using ADP 20 μM and thrombin receptor agonist peptide (TRAP) at 15 μM and 25 μM as agonists. Genomic DNA was genotyped for common CYP2C19 variants. Results: Increasing quartiles of 20 μM ADP induced platelet aggregation after clopidogrel loading were associated with increasing levels of TRAP mediated platelet aggregation. Patients in the highest quartile (clopidogrel non-responders) of post treatment ADP aggregation had significantly higher TRAP mediated aggregation than the patients in the lowest quartile (clopidogrel responders) [TRAP 15 μM: 79.6 ± 5% vs. 69.5 ± 8%, p < 0.001]. Conclusions: Non-responders to clopidogrel show increased residual platelet aggregation induced by TRAP, whereas clopidogrel responders exhibit attenuated response to TRAP. Addition of PAR-1 antiplatelet drugs may be most effective in patients with reduced clopidogrel response and high residual TRAP mediated platelet aggregation.

Original languageEnglish (US)
Pages (from-to)198-202
Number of pages5
JournalThrombosis Research
Volume130
Issue number2
DOIs
StatePublished - Aug 2012

Keywords

  • aggregation
  • clopidogrel
  • Platelet
  • thrombin

ASJC Scopus subject areas

  • Hematology

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