Aspirin Resistance: Clinical Significance and Genetic Polymorphism

Abstract

OBJECTIVE: To determine the prevalence, clinical implications and underlying mechanism of aspirin resistance in Chinese patients. METHODS: Platelet aggregation was determined by light transmission aggregometry (LTA) using four different inducers. Patients were divided into aspirin-resistant (AR), aspirin semi responder (ASR) and aspirin-sensitive (AS) groups, according to their LTA results. Aspirin resistance was assessed by thromboelastography (TEG, with arachidonic acid [AA] or adenosine diphosphate as inducers), serum/urinary 11-dehydrothromboxane B₂ (11-DH-TXB₂) assay, platelet function analyser-100 assay and P-selectin assay. Polymorphisms in the prostaglandin endoperoxide synthase 1 (PTGS1) gene (A842G, C50T, C22T, G128A, C644A and C714A), the PTGS2 gene (G765C) and the integrin β₃ (ITGB3) gene (C196T) were examined. RESULTS: The study included 360 aspirin-treated patients and 314 healthy controls. AS patients had significantly lower levels of 11-DH-TXB₂ than AR and ASR patients, and significantly lower levels of P-selectin than AR patients. TEG-AA was more sensitive, specific and consistent than P-selectin in detecting aspirin resistance. The frequency of the PTGS2 G765C mutation was significantly higher in the AR/ASR groups versus the AS group. CONCLUSIONS: TEG-AA was more sensitive, specific and consistent than the P-selectin assay for detecting aspirin resistance, and the PTGS2 G765C mutation may be related to aspirin resistance.