Protease activated receptor-1 (PAR-1) mediated platelet aggregation is dependent on clopidogrel response.
Thromb Res
; 130(2): 198-202, 2012 Aug.
Article
en En
| MEDLINE
| ID: mdl-22459907
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Plaquetas
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Ticlopidina
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Inhibidores de Agregación Plaquetaria
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Agregación Plaquetaria
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Receptor PAR-1
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Intervención Coronaria Percutánea
Límite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Thromb Res
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos