Aspirin Resistance: Clinical Significance and Genetic Polymorphism

Abstract

To determine the prevalence, clinical implications and underlying mechanism of aspirin resistance in Chinese patients. 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 thrombo elastography (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. 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. 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.