氯吡格雷在急性脑梗死的糖尿病患者中血小板抑制效应的研究
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摘要
目的用血栓弹力图(thromboelastograms,TEG)评价合并糖尿病的急性脑梗死患者正规使用氯吡格雷后血小板抑制率的变化及氯吡格雷抵抗情况。方法收集住院的急性脑梗死患者80例,其中糖尿病患者33例,非糖尿病患者47例,所有患者予以顿服氯吡格雷负荷量300 mg继以75 mg/d维持,在服用氯吡格雷3 d后和7 d后空腹抽取肘静脉血标本,用血栓弹力图(thromboelastograms,TEG)测定10μmol/L二磷酸腺苷(adenosine diphosphate,ADP)受体途径诱导的血小板抑制率,分析比较两组患者临床特征、血小板抑制率的差异和氯吡格雷抵抗情况。结果糖尿病组的空腹血糖(Fasting plasma glucose,FPG)和糖化血红蛋白(%)显著高于非糖尿病组,差异具有统计学意义(P<0.05)。糖尿病组3 d后和7 d的血小板抑制率显著低于非糖尿病组,差异具有统计学意义(P<0.05)。糖尿病组3 d和7 d后分别有11例(33.3%)、12例(36.4%)患者出现氯吡格雷抵抗的现象,显著高于非糖尿病组的6例(12.8%)、5例(10.6%),差异具有统计学意义(P<0.05)。结论糖尿病患者的血小板抑制率明显低于非糖尿病患者,更容易发生氯吡格雷抵抗现象。
Objective To evaluate the change of platelet inhibitory rate and the Clopidogrel resistance by thromboelastograms(TEG) after taking clopidogrel in patients with acute cerebral infarction and diabetes.Methods Eighty patients(33 diabetic and 47 nondiabetic patients) with acute cerebral infarction were recruited.All patients were treated with clopidogrel(300 mg loading dose followed by a dose of 75 mg/day),Whole blood samples were collected after clopidogrel was administered for 3 days and 7 days,the inhibitory rates of 10 μmol/L ADP receptor pathway in platelets were detected by TEG,characteristics and platelet inhibitory rate between groups were compared.Results The fasting plasma glucose(FPG) and glycosylated hemoglobin(%) in the diabetic group were significantly higher than those in the non-diabetic group(P<0.05).The platelet inhibition rate in diabetic group was significantly lower than that in non-diabetic group at 3 days and 7 days(P<0.05).The incidence of clopidogrel resistance in 11 patients(33.3%) and 12 patients(36.4%) in the diabetic group was significantly higher than that in the non-diabetic group 6(12.8%) and 5(10.6%).Conclusion Diabetic patients with platelet inhibition rate was significantly lower than non-diabetic patients.They have a higher ratio of clopidogrel resistance compared with nondiabetic subjects.
Objective To evaluate the change of platelet inhibitory rate and the Clopidogrel resistance by thromboelastograms(TEG) after taking clopidogrel in patients with acute cerebral infarction and diabetes.Methods Eighty patients(33 diabetic and 47 nondiabetic patients) with acute cerebral infarction were recruited.All patients were treated with clopidogrel(300 mg loading dose followed by a dose of 75 mg/day),Whole blood samples were collected after clopidogrel was administered for 3 days and 7 days,the inhibitory rates of 10 μmol/L ADP receptor pathway in platelets were detected by TEG,characteristics and platelet inhibitory rate between groups were compared.Results The fasting plasma glucose(FPG) and glycosylated hemoglobin(%) in the diabetic group were significantly higher than those in the non-diabetic group(P<0.05).The platelet inhibition rate in diabetic group was significantly lower than that in non-diabetic group at 3 days and 7 days(P<0.05).The incidence of clopidogrel resistance in 11 patients(33.3%) and 12 patients(36.4%) in the diabetic group was significantly higher than that in the non-diabetic group 6(12.8%) and 5(10.6%).Conclusion Diabetic patients with platelet inhibition rate was significantly lower than non-diabetic patients.They have a higher ratio of clopidogrel resistance compared with nondiabetic subjects.
引文
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[12]Westerbacka J,Yki-Jarvinen H,Turpeinen A,et al.Inhibition of plateletcollagen interaction:an in vivo action of insulin abolished by insulin resistance in obesity[J].Arterioscler Thromb Vasc Biol,2002,22(1):167-172.
[13]Lepantalo A,Virtanen KS,Heikkila J,et al.Limited early antiplatelet effect of 300 mg clopidogrel in patients with aspirin therapy undergoing percutaneous coronary interventions[J].Eur Heart J,2004,25(6):476-483.
[14]Ang L,Palakodeti V,Khalid A,et al.Elevated plasma fibrinogen and diabetes mellitus are associated with lower inhibition of platelet reactivity with clopidogrel[J].J Am Coll Cardiol,2008,52(13):1052-1059.
[15]Liu XL,Wang ZJ,Yang Q,et al.Impact of CYP2C19 polymorphism and smoking on response to clopidogrel in patients with stable coronary artery disease[J].Chin Med J(Engl),2010,123(22):3178-3183.
[16]石红婷,周伯荣,王融,等.脑梗死患者P2Y12与CYP2C19基因突变的临床学特征及其与氯吡格雷动态抵抗的相关性[J].中风与神经疾病杂志,2014,31(10):871-875.
[17]Wang Y,Wang Y,Zhao X,et al.Clopidogrel with aspirin in acute minor stroke or transient ischemic attack[J].N Engl J Med,2013,369(1):11-19.
[18]Ferreiro JL,Angiolillo DJ.Diabetes and antiplatelet therapy in acute coronary syndrome[J].Circulation,2011,123(7):798-813.
[19]Scheen AJ,Legrand D.Aspirin and clopidogrel resistance in patients with diabetes mellitus[J].Eur Heart J,2006,27(23):2900-2901.
[20]Ferreiro JL,Angiolillo DJ.Challenges and perspectives of antiplatelet therapy in patients with diabetes mellitus and coronary artery disease[J].Curr Pharm Des,2012,18(33):5273-5293.
[21]Alf-Aage PR,Harald A,Trine B,et al.The influence of CYP2C19*2polymorphism on platelet function testing during single antiplatelet treatment with clopidogrel[J].Thrombosis J,2011,9:4.
[2]Matetzky S,Shenkman B,Guetta V,et al.Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction[J].Circulation,2004,109(25):3171-3175.
[3]Gasparyan AY,Watson T,Lip GY.The role of aspirin in cardiovascular prevention:implications of aspirin resistance[J].J Am Coll Cardiol,2008,51(19):1829-1843.
[4]Coull AJ,Lovett JK,Rothwell PM.Population based study of early risk of stroke after transient ischaemic attack or minor stroke:implications for public education and organisation of services[J].BMJ,2004,328(7435):326.
[5]刘玲,侯华娟,刘亚红,等.用血栓弹力图评价阿司匹林及氯吡格雷在缺血性卒中患者中血小板抑制效应的研究[J].中风与神经疾病杂志,2012,29(5):446-449.
[6]Chen ZM,Jiang LX,Chen YP,et al.Addition of clopidogrel to aspirin in45,852 patients with acute myocardial infarction:randomised placebo-controlled trial[J].Lancet,2005,366(9497):1607-1621.
[7]Sofi F,Marcucci R,Gori AM,et al.Clopidogrel non-responsiveness and risk of cardiovascular morbidity.An updated meta-analysis[J].Thromb Haemost,2010,103(4):841-848.
[8]Geisler T,Anders N,Paterok M,et al.Platelet response to clopidogrel is attenuated in diabetic patients undergoing coronary stent implantation[J].Diabetes Care,2007,30(2):372-374.
[9]任艺虹,盖鲁粤,杨庭树,等.改良血栓弹力图法和流式细胞测定技术对血小板活性抑制程度的比较研究[J].中华心血管病杂志,2007,35(4):366-367.
[10]Feher G,Feher A,Pusch G,et al.Clinical importance of aspirin and clopidogrel resistance[J].World J Cardiol,2010,2(7):171-186.
[11]石红婷,周伯荣,王融,等.氯吡格雷抵抗在脑梗死患者中的动态观察[J].中国卒中杂志,2012(11):852-857.
[12]Westerbacka J,Yki-Jarvinen H,Turpeinen A,et al.Inhibition of plateletcollagen interaction:an in vivo action of insulin abolished by insulin resistance in obesity[J].Arterioscler Thromb Vasc Biol,2002,22(1):167-172.
[13]Lepantalo A,Virtanen KS,Heikkila J,et al.Limited early antiplatelet effect of 300 mg clopidogrel in patients with aspirin therapy undergoing percutaneous coronary interventions[J].Eur Heart J,2004,25(6):476-483.
[14]Ang L,Palakodeti V,Khalid A,et al.Elevated plasma fibrinogen and diabetes mellitus are associated with lower inhibition of platelet reactivity with clopidogrel[J].J Am Coll Cardiol,2008,52(13):1052-1059.
[15]Liu XL,Wang ZJ,Yang Q,et al.Impact of CYP2C19 polymorphism and smoking on response to clopidogrel in patients with stable coronary artery disease[J].Chin Med J(Engl),2010,123(22):3178-3183.
[16]石红婷,周伯荣,王融,等.脑梗死患者P2Y12与CYP2C19基因突变的临床学特征及其与氯吡格雷动态抵抗的相关性[J].中风与神经疾病杂志,2014,31(10):871-875.
[17]Wang Y,Wang Y,Zhao X,et al.Clopidogrel with aspirin in acute minor stroke or transient ischemic attack[J].N Engl J Med,2013,369(1):11-19.
[18]Ferreiro JL,Angiolillo DJ.Diabetes and antiplatelet therapy in acute coronary syndrome[J].Circulation,2011,123(7):798-813.
[19]Scheen AJ,Legrand D.Aspirin and clopidogrel resistance in patients with diabetes mellitus[J].Eur Heart J,2006,27(23):2900-2901.
[20]Ferreiro JL,Angiolillo DJ.Challenges and perspectives of antiplatelet therapy in patients with diabetes mellitus and coronary artery disease[J].Curr Pharm Des,2012,18(33):5273-5293.
[21]Alf-Aage PR,Harald A,Trine B,et al.The influence of CYP2C19*2polymorphism on platelet function testing during single antiplatelet treatment with clopidogrel[J].Thrombosis J,2011,9:4.