氯吡格雷、阿司匹林对高血压患者血小板微粒CD62p、GPⅡ b/Ⅲa的影响

目的 探讨血小板膜糖蛋白微粒CD62p、GPⅡb/Ⅲa与高血压的关系,以及抗血小板药物对其影响.方法 采用流式细胞术（FCM）和单克隆抗体标记法,检测60例高血压患者、20名健康对照者的血液标本,以20 μmol/L ADP为激活剂激活血小板,30例服用阿司匹林,30例服用氯吡格雷,检测高血压患者血小板膜糖蛋白微粒CD62p、GPⅡb/Ⅲa水平,观察药物对其的作用.结果 高血压组CD62p、GPⅡb/Ⅲa的百分率（85.3%±11.2%、91.6±12.4%）比正常对照组高（69.8%±8.9%、72.5%±10.2%）,P＜0.01,服用阿司匹林组CD62p、GPⅡb/Ⅲa的百分率降至（64.2%±9.6%、69.2%±9.8%）,P＜0.05与服药前有显著性差异,服用波立维组CD62p、GPⅡb/Ⅲa的百分率降至（39.8%±10.2%、32.8%±11.6%）,P＜0.01与服药前比较有显著性差异.结论 高血压与血小板膜糖蛋白微粒CD62p、GPⅡb/Ⅲa 的表达存在一定的联系,阿司匹林、氯比格雷可降低血小板微粒CD62p、GPⅡb/Ⅲa水平.     

脑梗死患者阿司匹林抵抗及相关基因多态性研究

目的探讨脑梗死患者阿司匹林抵抗（AR）发生率及环氧化酶-1（COX-1）基因C50T和环氧化酶-2（COX-2）基因G765C多态性与阿司匹林抵抗的相关性。方法634例首次发病的脑梗死患者,入院次13开始服用阿司匹林,服用阿司匹林治疗前和治疗7～10天后分别检N--磷酸腺苷（ADP）和花生四烯酸（AA）诱导的血小板聚集率（PAG）,并采用多聚酶链式反应结合限制性内切酶片段长度多态分析方法检测COX-1基因CSOT、COX-2基因G765C多态性。结果634例脑梗死患者中,阿司匹林抵抗（AR）者129例（20．35％）,阿司匹林半抵抗（ASR）28例（4．42％）,阿司匹林敏感（AS）477例（75．23％）。COX-1CSOT和COX-2G765C基因型及等位基因在ASR＋AR组及As组的比较差异无统计学意义（P〉0．05）;服用阿司匹林后7—10天,脑梗死患者AA诱导的血小板聚集率及ADP诱导的血小板聚集率分别下降80．00％及40．00％;无论COX-1C50T和COX-2G765C的哪种基因型均可使AA诱导血小板聚集率及ADP诱导血小板聚集率降低,但各种基因型在这些指标降低幅度的比较差异无统计学意义（P〉0．05）;COX-1基因CSOT和基因GCOX-2765C变异者AA诱导血小板聚集率在服阿司匹林前后均高于无变异者,差异有统计学意义（P〈0．05）。结论脑梗死患者阿司匹林抵抗发生率高,COX-1基因CSOT、COX-2基因G765C多态性与阿司匹林抵抗的发生无明显相关性,也不影响阿司匹林对血小板的反应性。     

心脑血管疾病患者发生阿司匹林抵抗现象的相关研究

门诊筛选具有阿司匹林（ASA）预防适应证的患者200例,服用ASA前后抽取静脉血,分别用二磷酸腺苷（ADP）、花生四烯酸（AA）诱导血小板凝集试验（PAgT）,检测血小板聚集率及血栓烷B2（TXB2）水平.结果患者中阿司匹林抵抗（AR）发生率为4.5%,阿司匹林半敏感（ASR）20.7%,AR及ASR患者中女性比率较阿司匹林敏感（AS）者高（P＜0.05）,吸烟者少（P＜0.01）;TXB2水平与AA、ADP诱导的血小板聚集率有较好的相关性.AA、ADP诱导的血小板聚集率、TXB2水平测定可作为口服ASA疗效监测的手段.     

复方丹参滴丸对冠心病患者阿司匹林抵抗的作用

目的:探讨复方丹参滴丸对冠心病阿司匹林抵抗患者二磷酸腺苷(ADP)、花生四烯酸(AA)诱导的血小板聚集率的影响。方法:根据AA和ADP作为诱导剂测定的血小板聚集功能,将39例阿司匹林抵抗患者随机分为2组。A组为常规阿司匹林治疗组(n=19),B组为阿司匹林联合复方丹参滴丸治疗组(n=20)。分别在治疗前以及治疗1个月后测定由ADP、AA诱导的血小板聚集率,比较2组治疗前后及治疗后不同组别上述指标的差异。结果:阿司匹林联合复方丹参滴丸治疗1个月后,可使冠心病阿司匹林抵抗患者血小板聚集率下降,与治疗前比较有显著性差异[(49.46%±5.18%)比(73.81%±2.86%),P=0.048 9];可使冠心病患者血尿酸水平下降,B组治疗后血尿酸水平为(421.69±34.01)μmol/L,较治疗前[(444.69±50.88)μmol/L]明显下降(P=0.038 9),与A组治疗后[(444.88±21.32)μmol/L]相比明显下降(P=0.042 2)。2组患者在治疗中未出现不良临床事件。结论:复方丹参滴丸对冠心病阿司匹林抵抗患者有抗血小板聚集作用,并且治疗后可降低血尿酸水平。     

急性冠脉综合征患者血小板聚集率、CD62p、Hs-CRP与尿11-脱氢-TXB2水平的动态变化分析

目的观察急性冠脉综合征患者1周指标血小板聚集率、CD62p、尿11-脱氢-TXB：水平与炎性因子Hs-CRP的动态变化。方法选取2006年4月～2007年2月，首都医科大学附属复兴医院年龄在43—90岁，符合急性冠脉综合征诊断标准的患者，不稳定心绞痛或急性心肌梗死的患者95例，入院前均服用口服阿司匹林0．1g，qd，至少1周以上。测定患者血小板聚集率、CD62p、Hs．CRP、尿11-脱氢-TXB2的入院时及1周时的水平。同时随访6个月时的临床终点事件的发生率，研究这些指标和临床终点事件的相关性。结果入院时AMI组ADP诱导血小板聚集率为（50．38±14．59）％，UAP组中ADP诱导血小板聚集率为（50．04±17．5）％，显著高于对照组[（36．56±10．47）％，P〈0．01]；入院时AMI组AA诱导血小板聚集率为（21．54±13．32）％，UAP组中AA诱导血小板聚集率为（18．68±12．79）％，显著高于对照组[（7．75±4．33）％，P〈0．01]；1周时急性心肌梗死组、不稳定心绞痛与对照组ADP诱导的血小板聚集率相比[（42．59±19．84）％、（43．61±19．59）％vs（36．56±10．47）％]差异无统计学意义；1周时急性心肌梗死组AA诱导的血小板聚集率为（14．32±14．44）％，与对照组AA诱导的血小板聚集率[（7．75±4．33）％]相比，差异有统计学意义（P〈0．05）；1周时不稳定心绞痛组AA诱导的血小板聚集率为（13．02±8．11）％，与对照组AA诱导的血小板聚集率[（7．75±4．33）％]相比，差异无统计学意义。入院时AMI组血小板CD62p为（33．61±19．33）％，UAP组中血小板CD62p为（27．09±15．69）％，高于对照组（16．92±8．73）％，P〈0．05：1周后两组血小板：AMI组血小板CD62p为（22．08±16．61）％及UAP组中血小板CD62p（20．96±11．52）％水平与对照组相比，差异无统计学意义。入院时AMI组尿11-脱氢-血栓素TXB：为722．99±637．25、UAP,组中尿11-脱氢-血栓素TXB，为699．56±587．46，显著高于对照组（42．28±35．02），P〈0．01；1周后两组AMI组尿11-脱氢-血栓素TXB2为84．56±50．35、UAP组中尿11-脱氢-血栓素TXB，为76．43±42．69，与对照组（42．28±35．02）相比，差异已无统计学意义。入院时AMI高敏c反应蛋白（36．33±26．04），UAP组中高敏C反应蛋白（9．39±6．40）高于对照组（1．56±0．75），P〈0．05；1周后AMI组Hs-CRP（2．98±1．12）、UAP组Hs-CRP（2．06±0．96）与对照组（1．56±0．75）相比，差异无统计学意义。除了Hs-CRP在AMI（36．33±26．04）、UAP（9．39±6．40）组中相比差异有统计学意义（P〈0．01），其他AMI与UAP组相比较ADP，AA诱导血小板聚集率、CD62p均差异无统计学意义。入院时ADP诱导的血小板聚集率与AA诱导的血小板聚集率正相关（相关系数0．274，P=0．007）；入院时尿11-DH-TXB，与ADP诱导的血小板聚集率正相关（相关系数0．411，P：0．008）；入院时尿11-DH-TXB：与AA诱导的血小板聚集率正相关（相关系数0．28，P=0．006）；血小板CD62p水平与高敏C-反应蛋白（Hs-CRP）正相关（相关系数0．309，P=0．002），差异均有统计学意义（P〈0．01）。结论AMI、UAP组中ADP、AA诱导的血小板聚集率、CD62p、Hs-CRP及尿11-TXB2均显著高于对照组；AMI、UAP患者血小板活化标志因子CD62p与Hs-CRP呈正相关，提示炎性因子及血小板的活化可能都足影响急性冠脉综合征患者病情发展及预后的重要因素，CD62p水平升高可能为提示支架术后患者易形成血栓的指标。尿11-脱氢血栓素B2（尿11-DH-TXB2）、高敏C反应蛋白（Hs-CRP）为影响临床终点事件的因素。     

脑梗死患者二级预防中阿司匹林抵抗现象及干预措施

目的：观察脑梗死二级预防中阿司匹林抵抗现象,并分析其干预措施。方法325例脑梗死患者于入院当天起每晚顿服拜阿司匹林200 mg,7～10 d后检测血小板聚集率（MAR）,筛选出阿司匹林抵抗、半反应者98例（随机分为3组,A组改用氯吡格雷,B组改用阿司匹林＋氯吡格雷,C组继续服用拜阿司匹林）和敏感者227例（续服拜阿司匹林）。10 d后复查MAR。结果与同组调整前比较,A组调整后花生四烯酸（ AA）诱导MAR升高,二磷酸腺苷（ADP）诱导MAR降低（P均＜0．05）;与同组调整前比较,B组调整后AA诱导、ADP诱导MAR均降低（P均＜0．05）。结论脑梗死二级预防中阿司匹林抵抗现象发生率高,阿司匹林联合氯吡格雷双重抗血小板治疗可有效改善阿司匹林抵抗。     

阿司匹林联合氯吡格雷治疗对缺血性脑卒中病人神经功能及血小板聚集率的影响

目的观察阿司匹林单用和与氯吡格雷联合治疗对缺血性脑卒中病人神经功能及血小板聚集率的影响。方法选择2015年1月—2016年12月住院诊治的缺血性脑卒中病人256例,按照入院顺序和治疗方案随机分为单药组与联合组,各128例。入选病人均给予缺血性脑卒中的常规治疗,单药组病人给予肠溶阿司匹林每日100 mg,联合组病人在单药组治疗方案基础上加用氯吡格雷每日75mg,疗程2周。比较两组病人的临床疗效、治疗前后神经功能缺损评分(NIHSS)和Barthel日常生活活动能力评定量表(ADL)及血小板聚集率[血小板颗粒膜蛋白140(GMP-140)水平及分别用二磷酸腺苷(ADP)和花生四烯酸(AA)为诱导剂的血小板聚集率]和不良反应发生情况的差异。结果联合组总有效率高于单药组(χ2=11.13,P0.01)。治疗前两组病人NIHSS和ADL评分、GMP-140水平、ADP和AA诱导的血小板聚集率差异无统计学意义(P0.05);治疗后两组病人NIHSS和ADL评分、GMP-140水平、ADP和AA诱导的血小板聚集率明显低于各组治疗前水平;与单药组比较,联合组的下降程度更显著(P0.05)。结论阿司匹林与氯吡格雷联合治疗可进一步改善缺血性脑卒中病人神经功能缺损情况,抑制血小板聚集,提高病人的生活能力。     

替格瑞洛与氯吡格雷在ACS并发T2DM行PCI患者中对血小板聚集功能影响的比较

目的 观察急性冠脉综合征（ACS）并发2型糖尿病（T2DM）行经皮腔内冠状动脉介入（PCI）治疗患者中替格瑞洛与氯吡格雷对血小板聚集功能影响的比较。 方法 回顾性的收集2013年3月~2015年3月我院ACS并发T2DM行PCI患者175例,按使用的抗血小板药物分为两组:替格瑞洛组（n=22）和氯吡格雷组（n=153）,采用光比浊法分析血小板聚集功能,比较两者血小板聚集功能的差异。 结果 花生四烯酸（AA）诱导的血小板聚集率:氯吡格雷组为（32±20）%,替格瑞洛组为（26±17）%,两组差异无显著性;二磷酸腺苷（ADP）诱导的血小板聚集率:氯吡格雷组为（51±18）%,替格瑞洛组（40±18）%,两组有显著性差异（P=0.01）。 结论 对于ACS并发T2DM行PCI患者,替格瑞洛较氯吡格雷显著减低ADP诱导的血小板聚集率,不影响AA诱导的血小板聚集率。     

通心络胶囊对冠心病病人阿司匹林抵抗的影响

目的观察通心络胶囊对冠心病病人阿司匹林抵抗（AR）的影响.方法选择冠心病并AR病人64例,分为联合治疗组（32例）及通心络组（32例）.联合治疗组予通心络胶囊与阿司匹林联合使用,通心络组则停用阿司匹林片两周后服用通心络胶囊.结果通心络组治疗总有效率为50.0%,联合治疗组总有效率为90.6%;两组血小板聚集率均明显降低.随诊9个月,均无严重急性心血管事件的发生,无并发症发生.结论对冠心病AR病人,通心络有较好效果,与阿司匹林联用效果更明显.     

高血压患者阿司匹林抵抗及相关因素分析

目的探讨高血压患者阿司匹林抵抗（AR）现象及其相关因素。方法选取81例高血压病患者,服用阿司匹林100 mg/d,服用时间≥2周。分别用二磷酸腺苷（ADP）、花生四烯酸（AA）作诱导剂检测血小板聚集率（PAG）。同时满足ADP诱导的PAG≥70%、AA诱导的PAG≥20%为AR,仅满足其中一项为阿司匹林半抵抗（ASR）,均不符合者为阿司匹林敏感（AS）。结果81例高血压患者中,AR＋ASR发生率为11.1%。AR＋ASR组较AS组合并不稳定型心绞痛比例及平均血小板体积显著增加（P〈0.05）。结论不稳定型心绞痛患者更容易发生AR,平均血小板体积增大可能对AR的发生产生影响。     

阿司匹林抑制房间隔或室间隔缺损封堵术后血小板聚集

目的 观察房间隔缺损（atrial septal defect,ASD）、室间隔缺损（ventricular septal defect,VSD）介入封堵术前后血小板聚集的变化并探讨封堵术后服用阿司匹林的合适剂量。方法 选择成功进行ASD、VSD介入封堵术的患者各16例．按口服阿司匹林肠溶片的剂量随机分为3mg／kg组和5mg／kg组,分别于术前、术后即刻、术后第4日抽静脉血并测定花生四烯酸（arachidonic acid,AA）、二磷酸腺苷（adenosine diphosphate,ADP）诱导的血小板聚集率。结果 ①ASD、VSD患者介入封堵术后血小板聚集率明显增加（P〈0．01）,术后第4日血小板聚集率明显下降（P〈0．01）;②术后口服阿司匹林3mg／kg组与5mg／kg两组患者介入封堵术后第4日血小板聚集率差异无统计学意义（P〉0．05）。结论 ASD或VSD封堵术后即刻血小板聚集明显增加,封堵术后第4日血小板聚集明显减弱,口服3mg／kg的阿司匹林抑制血小板聚集疗效类似5mg／kg。     

埃索美拉唑预防阿司匹林相关性胃肠损伤及其相互作用的研究

目的探讨埃索美拉唑是否会降低小剂量阿司匹林中发生胃肠损伤尤其是溃疡的风险,同时探讨其对阿司匹林抗血小板作用的影响。方法入选的95例心脑血管患者随机分为两组:对照组47例,单用阿司匹林,服用阿司匹林肠溶片100 mg,1次/d;联合组48例,服用同种剂量阿司匹林肠溶片联合埃索美拉唑20 mg,1次/d。对比两组胃镜下黏膜表现变化,记录其黏膜损伤以及溃疡发生情况。并在给药前1 d、服药后28 d分别测定血小板聚集率,比较两组血小板聚集率的差异。结果对照组胃肠黏膜损害者有29例(61.7%),其中消化性溃疡8例(17%),联合组发生胃黏膜损害者仅5例(10.4%),其中消化性溃疡发生者仅1例(2.1%),两组之间存在显著差异(P<0.05)。对照组及联合组治疗后较治疗前以花生四烯酸(ACA)和腺苷二磷酸(ADP)诱导的血小板聚集率均显著降低(P<0.05)。结论埃索美拉唑会降低小剂量阿司匹林治疗中发生溃疡的风险,且对阿司匹林的抗血小板作用无明显影响,尚需进一步扩大样本量的研究。     

Comparison of increased aspirin dose versus combined aspirin plus clopidogrel therapy in patients with diabetes mellitus and coronary heart disease and impaired antiplatelet response to low-dose aspirin

The effects of therapy with aspirin 300 mg/day and with combined aspirin 100 mg/day plus clopidogrel 75 mg/day on platelet function were compared in patients with diabetes mellitus and coronary artery disease and impaired antiplatelet responses to aspirin 100 mg/day. The study population consisted of 151 outpatients with type II diabetes mellitus and coronary artery disease who were taking aspirin 100 mg/day. Of the 151 patients, a subgroup of subjects with impaired aspirin response were selected on the basis of the results of platelet aggregometry. Nonresponsiveness to aspirin was defined as mean aggregation > or =69% with 3 micromol/L adenosine diphosphate and mean aggregation > or =70% with 2 micromol/L collagen. Aspirin semiresponders were defined as meeting 1 but not both of these criteria. Nonresponders and semiresponders were randomized equally to aspirin 300 mg/day and aspirin 100 mg/day plus clopidogrel 75 mg/day, and aggregation tests were repeated after 2 weeks. Sixty of the 151 patients with diabetes (40%) were found to respond to aspirin inadequately. Platelet aggregation induced by adenosine diphosphate and collagen decreased significantly after aspirin 300 mg/day or combined therapy. Combined treatment was found to have a stronger inhibitory effect on platelet aggregation induced by adenosine diphosphate than aspirin 300 mg/day (p = 0.002). Impaired aspirin response was resolved by increasing the aspirin dose or adding clopidogrel to aspirin (p <0.0001 for each). However, desired platelet inhibition was achieved in significantly more patients by combined treatment than by aspirin 300 mg/day (p <0.05). In conclusion, aspirin 100 mg/day does not inhibit platelet function adequately in a significant number of patients with diabetes mellitus and coronary artery disease. Increasing the aspirin dose to 300 mg/day or adding clopidogrel to aspirin can provide adequate platelet inhibition in a significant number of those patients with impaired responses to low-dose aspirin.     

Relation between atherosclerosis risk factors and aspirin resistance in a primary prevention population

Resistance to inhibition of platelet function by aspirin may contribute to future myocardial infarction and stroke. Adverse cardiovascular outcomes have been associated with aspirin resistance on several different platelet function assays, including the level of urinary 11-dehydro thromboxane B2 (Tx-M), platelet aggregation to arachidonic acid and adenosine diphosphate, and closure time on the platelet function analyzer-100. We examined the concordance of these aspirin-resistance assays and their relation to cardiovascular risk factors in a primary prevention population. Asymptomatic patients (n = 1,311) at increased risk for coronary heart disease were evaluated before and after 2 weeks of aspirin (81 mg/day). Aspirin resistance was defined according to published criteria for these 3 assays of platelet function. Subjects were characterized for the presence of atherosclerosis risk factors. Agreement among the 3 assays was poor. Only 5 patients met aggregation criteria for aspirin resistance. Attenuated suppression of urinary Tx-M by aspirin was associated with a greater atherosclerotic risk profile and Framingham risk score in multivariable regression analysis. Aspirin resistance by platelet function analyzer-100 was associated only with increased von Willebrand factor levels and not with atherosclerotic risk profile. In conclusion, in a primary prevention population, different published criteria for aspirin resistance classify distinct groups of patients as aspirin resistant with very little overlap. Higher Tx-M, which reflects decreased suppression of thromboxane production in vivo, is the only criterion associated with atherosclerosis risk factors, suggesting that this measurement may represent the most relevant approach for identifying asymptomatic subjects whose aspirin treatment will "fail."     

Aspirin-induced platelet inhibition in patients undergoing cardiac surgery

Platelet function and response to pharmacological inhibition are altered by cardiac surgery. For example, aggregation is increased early after aortic valve replacement (AVR) and platelet response to aspirin is often insufficient after coronary artery bypass grafting (CABG). We hypothesized that the effect of aspirin administration after cardiac surgery might be impaired due to platelet activation. Therefore, the antiplatelet effect of aspirin was compared in patients (n = 20 per group) after CABG and AVR surgery (bileaflet prosthesis). Arachidonic acid-induced aggregation (turbidimetry) and thromboxane formation (radioimmunoassay) were determined before and 1, 5, and 10 days after surgery. In CABG-patients, antiplatelet treatment had been discontinued 10 days before surgery. Oral aspirin was started on day 1 after CABG. AVR-patients did not receive oral aspirin. Before surgery, platelet aggregation and thromboxane formation were significantly higher in patients with aortic stenosis. After CABG, thromboxane formation was not significantly changed from control values before surgery (66 +/- 13% on day 10) despite oral aspirin treatment, whereas thromboxane formation in patients undergoing AVR significantly increased compared to values before surgery (216 +/- 29% on day 10). In both groups of patients, 100 micromol/l aspirin in vitro largely inhibited platelet function before surgery, with markedly attenuated effects after surgery. In conclusion, thromboxane formation increased after AVR but not after CABG. The antiplatelet effect of aspirin, therefore, may be impaired after CABG by increased platelet activity. An additional in vitro "resistance" of platelets was seen after both CABG and AVR.     

Comparison of platelet P2Y(12) ADP receptor-mediated pathway inhibition in triple versus dual antiplatelet therapy as assessed by VASP-phosphorylation in Japanese patients undergoing coronary stenting

Despite wide interindividual variability in response to clopidogrel, platelet P2Y(12) ADP receptor inhibition in Japanese patients has not been fully studied using specific methodology. This study compared platelet P2Y(12) ADP receptor inhibition during treatment with clopidogrel versus clopidogrel plus cilostazol in patients undergoing coronary stenting. Forty-two patients in whom platelet function was measured within 2 months after coronary stenting were enrolled. All patients were treated with aspirin 100 or 200 mg/day, and were divided into a dual therapy group (aspirin plus clopidogrel 75 mg/day; n = 34) and a triple therapy group (aspirin plus clopidogrel 75 mg/day plus cilostazol 200 mg/day; n = 8). Vasodilator-stimulated phosphoprotein (VASP) phosphorylation analysis and 5 and 20 μmol/L-induced maximal platelet aggregation were assessed. No differences were found in baseline characteristics except for a higher incidence of diabetes mellitus (DM) in the triple therapy group. Although there were no differences in platelet aggregation between the 2 groups, VASP index was significantly lower in the triple therapy group than in the dual therapy group (23.1 ± 15.3% versus 51.2 ± 19.9%; P = 0.001). The rate of low responsiveness to clopidogrel, defined by VASP index > 50%, was lower in the triple therapy group than in the dual therapy group (12.5% versus 55.9%; P = 0.047). Similarly, in DM patients the triple therapy group had a lower VASP index compared with the dual therapy group (23.1 ± 15.3% versus 47.0 ± 23.5%; P = 0.015).Clopidogrel plus cilostazol is more effective in inhibiting the platelet P2Y(12) ADP receptor pathway than clopidogrel alone. This may be useful for reducing clopidogrel resistance in Japanese patients.     

Comparative inhibitory effects of cilostazol and ticlopidine on subacute stent thrombosis and platelet function in acute myocardial infarction patients with percutaneous coronary intervention

We compared the effects of ticlopidine and cilostazol on the prevention of subacute stent thrombosis (SAT) in acute myocardial infarction (AMI) patients with stenting. We also analyzed the cause of the difference by measuring platelet aggregation activity. Consecutive patients who underwent successful stenting for AMI between March 2001 and March 2004 were analyzed. In addition to aspirin (100 mg/day), cilostazol (200 mg/day) was administered to 99 cases between March 2001 and May 2002 and ticlopidine (200 mg/day) was administered to 85 cases between June 2002 and February 2004. The incidence of SAT within four weeks after stenting was analyzed. Thirty-eight AMI patients were randomized and their platelet aggregation activity was measured using a laser-scattered aggregometer (18 cases in the cilostazol group and 20 cases in the ticlopidine group). SAT did not occur in the ticlopidine group while 5 cases (5.1%) of SAT occurred in the cilostazol group (P < 0.05). The inhibitory activity of cilostazol for ADP-induced platelet aggregation was lower than that of ticlopidine (P < 0.05). Cilostazol with aspirin after stenting in AMI patients showed more frequent SAT than ticlopidine with aspirin. One of the causes for this difference was speculated to be the weaker inhibitory activity of cilostazol for ADP-induced platelet aggregation.     

Aspirin-induced platelet inhibition in patients undergoing cardiac surgery

Platelet function and response to pharmacological inhibition are altered by cardiac surgery. For example, aggregation is increased early after aortic valve replacement (AVR) and platelet response to aspirin is often insufficient after coronary artery bypass grafting (CABG). We hypothesized that the effect of aspirin administration after cardiac surgery might be impaired due to platelet activation. Therefore, the antiplatelet effect of aspirin was compared in patients (n?=?20 per group) after CABG and AVR surgery (bileaflet prosthesis). Arachidonic acid-induced aggregation (turbidimetry) and thromboxane formation (radioimmunoassay) were determined before and 1, 5, and 10 days after surgery. In CABG-patients, antiplatelet treatment had been discontinued 10 days before surgery. Oral aspirin was started on day 1 after CABG. AVR-patients did not receive oral aspirin. Before surgery, platelet aggregation and thromboxane formation were significantly higher in patients with aortic stenosis. After CABG, thromboxane formation was not significantly changed from control values before surgery (66?±?13% on day 10) despite oral aspirin treatment, whereas thromboxane formation in patients undergoing AVR significantly increased compared to values before surgery (216?±?29% on day 10). In both groups of patients, 100?µmol/l aspirin in vitro largely inhibited platelet function before surgery, with markedly attenuated effects after surgery. In conclusion, thromboxane formation increased after AVR but not after CABG. The antiplatelet effect of aspirin, therefore, may be impaired after CABG by increased platelet activity. An additional in vitro “resistance” of platelets was seen after both CABG and AVR.     

Overestimation of platelet aspirin resistance detection by thrombelastograph platelet mapping and validation by conventional aggregometry using arachidonic acid stimulation.

OBJECTIVES: This study sought to determine the prevalence of platelet aspirin resistance using methods that directly indicate the degree of platelet cyclooxygenase inhibition. BACKGROUND: Aspirin resistance in platelets may be overestimated by nonspecific laboratory measurements that do not isolate cyclooxygenase activity. METHODS: Arachidonic acid (AA)-induced light-transmittance platelet aggregation (LTA) and thrombelastography (TEG) platelet mapping were performed on the blood of healthy subjects (n = 6) before and 24 h after receiving 325 mg aspirin, and on 223 patients reporting compliance with long-term daily aspirin treatment (n = 203 undergoing percutaneous intervention [PCI] and n = 20 with a history of stent thrombosis). Aspirin resistance was defined as >20% aggregation by LTA or >50% aggregation by TEG. RESULTS: In healthy subjects, AA-induced aggregation by LTA was 82 +/- 10% before and 2 +/- 1% at 24 h after aspirin (p < 0.001), and aggregation by TEG was 86 +/- 14% before and 5 +/- 7% at 24 h after aspirin (p < 0.001). In compliant patients, AA-induced aggregation by LTA was 3 +/- 2% before PCI and 3 +/- 2% after PCI (p = NS), and aggregation by TEG was 5 +/- 9% before PCI and 6 +/- 14% after PCI (p = NS). Seven PCI patients were noncompliant, and all were aspirin sensitive after in-hospital aspirin treatment. Among 223 patients, only one patient ( approximately 0.4%) was resistant to aspirin treatment. CONCLUSIONS: Platelet aspirin resistance assessed by methods that directly indicate inhibition of cyclooxygenase is rare in compliant patients with coronary artery disease.     

老年心血管疾病中阿司匹林抵抗现象的研究

目的研究不同剂量阿司匹林对阿司匹林抵抗的影响。方法68例本院门诊或住院老年心脑血管疾病患者,随机分为阿司匹林低剂量组(100mg/天)及阿司匹林高剂量组(300mg/天),分别测定阿司匹林治疗前和治疗14天后血小板聚集率和血栓素B2水平。结果不同剂量阿司匹林均能产生有效的抗血小板作用,两组均有阿司匹林抵抗,低剂量组占40%,高剂量组占30.3%。在不稳定性心绞痛和稳定性心绞痛患者之间,阿司匹林抵抗发生率有统计学差异(P<0.01),不稳定性心绞痛患者阿司匹林抵抗发生率较高。结论无论阿司匹林治疗剂量高低,老年心脑血管疾病患者中均有部分患者出现阿司匹林抵抗,不稳定性心绞痛影响较明显。