Protease activated receptor-1 (PAR-1) mediated platelet aggregation is dependant on clopidogrel response
Thrombosis Research, 07/31/2012
Kreutz RP et al. - Non-responders to clopidogrel show increased residual platelet aggregation induced by TRAP, whereas clopidogrel responders exhibit attenuated response to thrombin receptor agonist peptide (TRAP). Addition of protease activated receptor-1 (PAR-1) antiplatelet drugs may be most effective in patients with reduced clopidogrel response and high residual TRAP mediated platelet aggregation.Methods
- Platelet aggregation was measured in 55 patients undergoing elective PCI at 16–24hours after 600mg 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.
- 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].