| Background: Aspirin and clopidogrel are the most commonly used drugs for anti-platelet aggregation in clinical practice.The combination of Aspirin and clopidogrel has also been proved to be a safe and effective treatment by international clinical trials.However,multiple factors can affect the efficacy of anti-platelet drugs in the clinical,such as: the patients age,disease history,living habits,genetic factors,drug interactions,etc..Therefore The influence of genetic factors on anti-platelet aggregation drugs efficacy has become a key research direction.As a pro-drug of anti-platelet aggregation,clopidogrel relies on the active metabolite of CYP2C19 to exercise the function of anti-platelet.Many clinical studies have shown that the genetic polymorphism of CYP2C19 is a major factor affecting the metabolism of clopidogrel.The patients can be classified according to the CYP2C19 genotype,such as ultrafast metabolites(single or double mutations of CYP2C19*17(CC→TT or CT)with normal CYP2C19* 2 and CYP2C19* 3(GG)),Fast metabolizing type(normal CYP2C19* 17,CYP2C19* 2 and CYP2C19* 3)Special intermediate metabolites: any single mutation of CYP2C19* 2 or CYP2C19* 3withsingle or double mutation of CYP2C19* 17,Intermediate metabolite type(single mutation of CYP2C19* 2 or CYP2C19* 3 withnormal CYP2C19* 17),Slow metabolizing type(double mutation of CYP2C19* 2 or CYP2C19* 3 respectively,or signal mutation of both CYP2C19* 2 and CYP2C19* 3 with normal CYP2C19* 17.Less active metabolites of routine dosage clopidogrel is produced in slow-metabolic patients,which decreases the ability of anti-platelet aggregation and improves the risk of thrombosis,while moreactive metabolites of routine dosage clopidogrel is produced in ultra-rapid metabolic patients,which increases the bility of anti-platelet aggregation and improves the risk of bleeding disorders.There are significant individual differences in response to aspirin efficacy among different patients in the clinic,while gene polymorphism is one of the main reasons.Platelet endothelial aggregation receptor 1(PEAR1)is involved in the induction of platelet-contact activation.The genetic variation of PEAR1 may lead to aspirin resistance,and its rs12041331(G>A)gene polymorphism is significantly correlated with PEAR1 protein expression.The PEAR1 GG type responds best to aspirin,followed by the PEAR1 GA type,and the PEAR1 AA type is the worst.Objective: By investigating the consistency and correlation between the gene polymorphisms of anti-platelet aggregation of clopidogrel and aspirin and thromboelastography,this paper aims to confirm the consistency of the genetic polymorphism of CPY2C19 and PEAR1 and the results of thromboelastography of the perioperative patients after intracranial cerebral vascular stenting.,and study the effects of PEAR1 and CYP2C19 gene polymorphisms on the efficacy of aspirin and clopidogrel in perioperative patients after intracranial stenting,providing references for personalized medication,ensurance of efficacy of drug therapy and the service level of pharmacy in the clinical treatment processMethodology: Perioperative patients who underwent intracranial stenting were treated with oral clopidogrel and aspirin in combination for antiplatelet aggregation therapy.The anti-platelet aggregation drug was administered orally at least 3-5 days,and then the CYP2C19 and PEAR1 genotypes were determined by PCR-RFLP,and the platelet inhibition rate was measured by TEG.The results of the test data of the patient’s genotype and thromboelastogram were recorded in detail.Follow-up of 100 patients with primary adverse cerebral vascular events and ischemic events for 1 month were used to determine the distribution of aspirin and clopidogrel gene polymorphisms in perioperative patients after intracranial cerebral vascular stenting and the correlation between genotype polymorphism and platelet aggregation rate detected by thromboelastography.Results:(1)Among the 500 patients enrolled in the screening,there were 225 cases of clopidogrel metabolites,accounting for 45%,215 cases of intermediate metabolites,accounting for 43%,and 60 cases of slow metabolism,accounting for 12 %.The thromboelastogram of 315 patients was tested.The results showed that 230 patients(ADP% < 30%),which accounted for 73.02%,did not achieve the platelet inhibition rate.(2)170 genotypes responsed well to aspirin,accounting for 34%.A total of 300 genotypes responsed to aspirin,accounting for 60%.A total of 6 genotypes with poor response to aspirin accounted for 6%.Among the 500 patients with thromboembolic maps,8 patients(AA% < 30%),which accounted for 8%,did not achieve the platelet inhibition rate.(3)AA% or ADP% < 30% is defined as high therapeutic platelet reactivity by platelet inhibition rate,and AA% or ADP% > 30% is defined as non-high therapeutic platelet reactivity.According to the statisticalresults,there were 8 cases of high-treatment platelet reactivity to aspirin in the 500 patients with perioperative cranial stenting,accounting for 8%.Of the 315 patients who underwent intracranial stenting,46 patients had high platelet reactivity to clopidogrel,accounting for 73.02%.(4)According to the PEAR1 genotype,the patients’ response to aspirin were devided into three types : 34% were fast response type,60% were intermediate response type,and 6%(6/100)were slow response type.According to the PEAR1 genotype,high therapeutic platelet reactivity was different,among which fast response,medium response and slow response types accounting for 0,87.5% and 12.5%,respectively.(5)According to the different results of detecting CYP2C19 genotype,the patients’ response to clopidogrel metabolic were devided into three types: 46.03% is fast metabolizing type;42.86% is an intermediate metabolite type;and 11.11% is a slow metabolizing type.According to the CYP2C19 genotype,the fast,medium and slow metabolites in patients with high therapeutic platelet reactivity accounted for 41.30 %,15.22% and 43.48%,respectively.(6)Ten(2%)ischemic events and one case of bleeding(1%)occured during the 3-month follow-up. |
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