The Occurrence And Mechanism Of Aspirin Resistance After OPCABG

Objective:The aim of this study was to investigate the prevalence of the perioperative aspirin resistance?AR?after off-pump coronary artery bypass graft?OPCABG?,and establish methods to determine reticulated platelet?RP?in whole blood?WB?,and cyclooxygenase?COX?-1,COX-2 and P-selectin in platelet-rich plasma?PRP?by flow cytometry?FCM?,and observe their dynamic change in the perioperative period of OPCABG surgery,by which to explore the mechanism of the perioperative aspirin resistance.Methods:We recruited 30 coronary artery disease?CAD?patients who were to receive OPCABG and had withdrawn aspirin and clopidogrel for at least 7 days.Aspirin treatment was re-initiated to all patients early after the OPCABG surgery.Patients'venous blood was drawn on the day before and on days 1,4,8 after the surgery after overnight fasting.The WB was processed and incubated with the thiazole orange?TO?,and PRP was incubated with the fluorescence labeled antibody.The positive percent of RP and COX-1,COX-2 and P-selectin were detected by FCM.In the meantime,the arachidonic acid?AA?induced platelet aggregation(PL_AA)was tested by the light transmission aggregometer?LTA?.A PL_AA of more than 20%after re-initiating aspirin treatment of more than 24 hours was defined as post-operative aspirin resistance.Major in-hospital adverse cardiovascular events?MACE?were followed up after the surgery.The results were analyzed using the statistical software of SPSS 18.0.Results:Aspirin treatment was re-initiated to all patients 37.7±7.8 hours after the surgery.The prevalence of aspirin resistance was 53.3%24 hours after the patients'taking first aspirin,and down to 16.7%48 hours after the patients'taking first aspirin.The PL_AAA levels declined to lower than 20%in all patients 7 days after re-initiating aspirin treatment.The platelet count decreased significantly on day 1 after the surgery compared with that before surgery[?146.73±8.800?×10⁹/L vs?194.50±11.40?×10⁹/L,P=0.009],and climbed to a significantly higher level on the 8th day after the surgery[?236.08±12.3?×10⁹/L vs?194.50±11.40?×10⁹/L,P=0.038].The COX-1 level did not show significant change during the peri-operative period.However,the positive percentages of both RP and COX-2 were significantly increased after the surgery and reached their peak levels on the 4th day after re-initiating aspirin treatment[1.05?0.30,2.37?vs 0.40?0,0.70?,P=0.001;?7.30±0.69?%vs?4.87±0.64?%,P=0.017].By contrast,the P-selecin level declined significantly on the 4th and the 8th days compared with the pre-operative level[?4.17±1.10?%vs?11.38±1.30?%,P=0.000;?5.91±1.40?%vs?11.38±1.30?%,P=0.002].One patient died of multiple organs dysfunction syndrome?MODS?during the hospitalization.Conclusion:The prevalence of aspirin resistance is as high as 53.3%in CAD patients after receiving OPCABG surgery.The post-operative aspirin resistance appears mostly within 3 days after the surgery and disappears basically 1 week later.The significantly increased RP level and COX-2 expression after the surgery may be a major reason of the post-operative AR.