血小板功能及抗血小板药物疗效检测的研究进展

在过去10年中,冠脉内支架植入术已成为冠心病血运重建的主要方式。术后双抗血小板治疗不能完全阻止支架内血栓事件的发生,抗血小板药物抵抗可能是其原因之一。目前,有许多方法可以检测血小板功能,以评价抗血小板药物的疗效。本研究介绍了血小板功能检测方法,探讨了其临床应用前景,以期指导抗血小板药物的应用,从而改善临床预后。     

Predictive value of antiplatelet resistance on early stent thrombosis in patients with acute coronary syndrome

Background  Despite outstanding antiplatelet properties of aspirin and clopidogrel, some patients taking these drugs continue to suffer complications. Antiplatelet resistance appears to be a new prognostic factor in acute coronary syndrome patients for clinical events associated with stent thrombosis (ST). However, there is no optimal method to identify it and assess its correlation to clinical outcomes. This study sought to evaluate the predictive value of antiplatelet resistance assessed by whole blood impedance aggregometry for the risk of early ST in patients with acute coronary syndrome who underwent coronary stenting.

Methods  Platelet responses to aspirin and clopidogrel in 86 patients with acute coronary syndrome were measured by whole blood impedance aggregometry. Spontaneous platelet aggregation was defined as antiplatelet resistance identified by the increased electrical impedance. The clinical endpoint was early stent thrombosis during 30-day follow-up after coronary stenting.

Results  The prevalence of aspirin resistance, clopidogrel resistance and dual resistance of combined clopidogrel and aspirin resistance were 19.8%, 12.8% and 5.8% respectively. Diabetes, female and higher platelet counts were more frequently detected in clopidogrel-resistant and dual-resistant patients. During 30-day follow-up, the patients with clopidogrel resistance and dual resistance had higher incidence of early stent thrombosis (18.2% vs. 1.3%, 40.0% vs. 1.2%, P <0.05). Binary Logistic Regression analysis indicated that dual resistance remained an independent predicator for early stent thrombosis (odds ratio 34.064, 95% CI 1.919–604.656, P=0.016).

Conclusions  Antiplatelet resistance assessed by whole blood impedance aggregometry is paralleled to clinical events, and dual antiplatelet resistance is an independent predicator for early stent thrombosis in patients with acute coronary syndrome. As a physiological assessment of platelet reactivity, whole blood impedance aggregometry is a convenient and accurate option for measuring antiplatelet resistance and hence predicting early stent thrombosis.

     

Drug-eluting coronary stents--a note of caution

There are two types of coronary stents: bare-metal stents (BMS) that cost about $800 each, and drug-eluting stents (DES) that cost about $3,300 each. DES reduce the rate of restenosis but have a higher incidence of late stent thrombosis, particularly if dual antiplatelet therapy with aspirin and clopidogrel is interrupted. Stent thrombosis has a myocardial infarction rate of 70% and a mortality rate of 31%-45%. Randomised studies of BMS versus DES show no increase in myocardial infarction or death with DES in simple coronary lesions, but in clinical practice, DES are mainly used in complex coronary disease where the rate of stent thrombosis is higher. Registry data suggest an increased rate of death and myocardial infarction of 0.5%-1.0% per annum with DES. Clinicians need to be aware of the risks associated with prematurely ceasing dual antiplatelet therapy in patients with DES.     

垠艺支架与Firebird支架治疗冠心病合并糖尿病患者疗效比较

目的:探讨药物涂层支架在冠心病合并糖尿病患者介入治疗中的临床疗效。方法:并发糖尿病的冠心病患者90例常规冠状动脉造影,进行经皮冠状动脉介入治疗,其中44例植入国产雷帕霉素药物涂层支架(Firebird组),46例植入国产紫杉醇药物涂层支架(垠艺组),术前术后常规使用阿司匹林和氯吡格雷,术后进行随访。结果:冠状动脉造影显示2支以上血管病变占83.3%,Firebird组植入雷帕霉素药物涂层支架77枚,垠艺组植入垠艺支架82枚,所有患者均获得成功。平均随访6.2±1.3个月,其中Firebird组复发心绞痛3例,1例发生心肌梗死。垠艺组复发心绞痛3例,1例发生心肌梗死。Firebird组发生再狭窄2例,垠艺组发生再狭窄2例。两组无支架内血栓形成和死亡。结论:垠艺支架对冠心病并发糖尿病患者的近期疗效与Firebird支架相似。     

Effect of polymorphism and type II diabetes on aspirin resistance in patients with unstable coronary artery disease

Background  Aspirin is widely used in the secondary prevention of coronary artery diseases, including myocardial infarction, stroke, and vascular related deaths. However, the antiplatelet effect of aspirin appears to be variable and aspirin resistance (AR) is currently still controversial for Chinese patients. The aim of this study was to describe the prevalence of AR, and identify possible risk factors associated with a lack of response to aspirin treatments in patients with unstable coronary artery disease.

Methods  Platelet function tests with arachidonic acid (ARA) and urinary 11-dehydro-thromboxane B2 (11-DH-TXB2) concentrations were performed in 262 patients with unstable coronary artery disease who had not been taking aspirin before admission. ARA induced platelet aggregation and 11-DH-TXB2 were detected to evaluate the functional and biochemical responses to aspirin before and on days 1, 4, and 10 after aspirin administration. Six-month follow-up was completed in patients who developed AR to evaluate the effect of aspirin in a long-term treatment. GP1Bα (C1018T), Pl (A1/A2), P2Y1(A1622G), TBXA2R (T924C) were also detected to evaluate the influence of genetic variant on aspirin responsiveness.

Results  A total of 8.8% of patients were indentified as AR at the first day after aspirin treatment. The level of urine 11-DH-TXB2 in the AR group was higher compared to non-AR group (P <0.05). There was no relationship between ARA induced platelet aggregation and urinary 11-DH-TXB2 levels (r=0.038, P=0.412). The results of DNA sequencing showed that TBXA2R-924TT homozygotes had a significantly high rate of AR. Logistic regression demonstrated that diabetes was an independent risk factor of AR.

Conclusions  In the beginning period of administration, aspirin was not a sufficient factor that inhibits platelet aggregation. TBXA2R-924T allele was involved in AR. Diabetes was an independent risk factor of AR.

     

血栓弹力图对冠状动脉粥样硬化性心脏病经皮冠状动脉介入术后抗血小板治疗患者血小板聚集抑制效果的评价

目的探讨血栓弹力图(TEG)对冠状动脉粥样硬化性心脏病(冠心病)经皮冠状动脉介入术(PCI)后抗血小板治疗患者血小板聚集抑制效果的评价。方法选择2017年1月至2018年12月我院收治的200例行PCI术后抗血小板治疗的冠心病患者作为研究对象,采用随机数表法分为对照组100例和观察组100例。对照组患者术前口服300 mg阿司匹林及300 mg硫酸氢氯吡格雷片,PCI术后口服100 mg阿司匹林,每日1次,75 mg氯吡格雷,每日1次。观察组患者术前口服300 mg阿司匹林及180 mg替格瑞洛口服,PCI术后口服100 mg阿司匹林,每日1次,90 mg替格瑞洛,每日1次,经TEG观察2组患者术后花生四烯酸(AA)及腺苷二磷酸(ADP)途径下凝血反应时间、血凝块形成时间、最大波幅及角度等TEG参数值及血小板聚集抑制效果。结果术后,观察组AA及ADP途径下凝血反应时间、血凝块形成时间长于对照组,最大波幅低于对照组,角度小于对照组,血小板抑制效果优于对照组,差异有统计学意义(P<0.05)。结论在TEG监测显示,阿司匹林联合替格瑞洛抗血小板聚集效果优于阿司匹林联合氯吡格雷,其可监测冠心病PCI术后抗血小板治疗患者血小板聚集抑制效果,利于临床监测结果指导调整抗血小板治疗方案,改善预后。     

Earlier application of loading doses of aspirin and clopidogrel decreases rate of recurrent cardiovascular ischemic events for patients undergoing percutaneous coronary intervention

Background  Aspirin and clopidogrel resistance plays a significant role in the development of cardiovascular ischemic events for ninety patients undergoing percutaneous coronary intervention. Recent studies have indicated that increasing the dose of antiplatelet drugs maybe a potent method to improve the inhibition of platelet aggregation.

Methods  Thrombelastograph (TEG) determinations were used to evaluate the effect of antiplatelet therapy. According to the results, 90 patients were divided into three groups and given different doses of aspirin and clopidogrel. Thirty patients with both an inhibition rate of aspirin >50% and an inhibition rate of clopidogrel >50% were defined as the control group. Sixty patients with an inhibition rate for aspirin <50% and an inhibition rate for clopidogrel <50% were defined as the resistance group. Patients in resistance group were randomly assigned to be given a routine dose (100 mg aspirin plus 75 mg clopidogrel per day, which we called a resistance plus routine dose group, R+R) and a loading dose (200 mg aspirin and 150 mg clopidogrel per day, which we called resistance plus loading dose group, R+L) of antiplatelet therapy. A 12-month follow-up was observed to examine the change of inhibition rate of antiplatelet therapy and to estimate the relationship between inhibition rate and the occurrence of cardiovascular ischemic events.

Results  After 6 months of antiplatelet therapy, the inhibition rate of aspirin in the R+L group increased from (31.4±3.7)% to (68.6±7.1)%, which was significantly higher than that in R+R group, (51.9±8.2)% (P <0.01). The inhibition rate of clopidogrel in the R+L group increased from (22.1±3.8)% to (60.2±7.4)%, which was significantly higher than in the R+R group, (45.9±4.3)% (P <0.01). The occurrence rates of cardiovascular ischemic events, stent thrombosis, recurrent unstable angina and myocardial infarction in the R+R group were 20%, 36% and 17%, respectively. Occurrence was significantly increased compared with that in the control group, 3%, 10% and 1%, respectively (P <0.01). In contrast, the occurrence rates in the R+L group (10%, 23% and 6%, respectively) were attenuated compared with those in the R+R group (P <0.01), although still higher than in the control group (P <0.01).

Conclusions  Almost all of the cardiovascular ischemic events occurred in the first six months after percutaneous coronary intervention. According to the result of TEG determinations, earlier application of a loading dose of aspirin and clopidogrel can decrease the rate of recurrent cardiovascular ischemic events.

     

Platelet function monitoring guided antiplatelet therapy in patients receiving high-risk coronary interventions

Background Large-scale clinical trials have shown that routine monitoring of the platelet function in patients after percutanous coronary intervention （PCI） is not necessary. However, it is still unclear whether patients received high-risk PCI would benefit from a therapy which is guided by a selective platelet function monitoring. This explanatory study sought to assess the benefit of a therapy guided by platelet function monitoring for these patients. Methods Acute coronary syndrome （ACS） patients （n=384） who received high-risk, complex PCI were randomized into two groups. PCI in the two types of lesions described below was defined as high-risk, complex PCI： lesions that could result in severe clinical outcomes if stent thrombosis occurred or lesions at high risk for stent thrombosis. The patients in the conventionally treated group received standard dual antiplatelet therapy. The patients in the platelet function monitoring guided group received an antiplated therapy guided by a modified thromboelastography （TEG） platelet mapping： If inhibition of platelet aggregation （IPA） induced by arachidonic acid （AA） was less than 50% the aspirin dosage was raised to 200 mg/d; if IPA induced by adenosine diphosphate （ADP） was less than 30% the clopidogrel dosage was raised to 150 mg/d, for three months. The primary efficacy endpoint was a composite of myocardial infarction, emergency target vessel revascularization （eTVR）, stent thrombosis, and death in six months. Results This study included 384 patients; 191 and 193 in the conventionally treated group and platelet function monitoring guided group, respectively. No significant differences were observed in the baseline clinical characteristics and interventional data between the two groups. In the platelet function monitoring guided group, the mean IPA induced by AA and ADP were （69.2＋24.5）% （range, 4.8% to 100.0%） and （51.4＋29.8）% （range, 0.2% to 100.0%）, respectively. The AA- induced IPA of forty-three （22.2%）     

哈尔滨地区心脑血管病患者中阿司匹林抵抗的探讨

目的研究哈尔滨地区心脑血管病患者中发生阿司匹林抵抗(AR)概况,并探讨其预测因子。方法110例病情稳定的心脑血管病住院患者,每日服用阿司匹林100mg,连服7天,第8天晨起采取空腹静脉血,分别以二磷酸腺苷(ADP)和花生四烯酸(AA)为诱导剂,检测血小板聚集功能。结果患者中AR发生率为0,阿司匹林半敏感(ASR)者占7．3％,女性较多(男：女,75．6％与40．5％,P=0．002),吸烟者亦较多(37．5％与17．5％,P=0．001)。结论阿司匹林用于抗血小板治疗及预防动脉粥样硬化事件的心脑血管患者中,若有AR或ASR存在可选用其他安全有效的抗血小板制剂,预测AR及抗血小板治疗个体化,将是抗血小板治疗的发展方向。     

老年冠状动脉临界病变患者阿司匹林抵抗临床特征分析

【目的】分析老年冠状动脉临界病变患者阿司匹林抵抗临床特征。【方法】人选老年冠状动脉临界病变患者320例，入院检测血脂、血常规和炎症指标，口服小剂量阿司匹林（100mg／a），2周后检测血小板功能，根据血小板功能分为阿司匹林抵抗组和阿司匹林敏感组。分析以上检测指标同阿司匹林抵抗的关系。【结果】阿司匹林抵抗的发生率为14％，阿司匹林抵抗组体重指数、糖尿病人数和血小板数量明显高于阿司匹林敏感组，而在性别、年龄、血压、血脂和炎症指标上两组无明显差异。【结论】高体重指数、糖尿病和血小板数量偏高者更易于阿司匹林抵抗。     

Gender difference on five-year outcomes of EXCEL biodegradable polymer-coated sirolimus-eluting stents implantation: results from the CREATE study

Background The gender difference on long-term outcome in unselected patients after percutaneous coronary intervention (PCI) has not yet been fully investigated.This study aimed to evaluate the gender d...     

氯吡格雷低反应性与CYP2C19基因多态性分布的研究

氯吡格雷是临床常用的抗血小板药物,在体内需通过CYP450酶的转变而发挥其抑制血小板聚集的作用,能有效降低动脉内及术后支架内血栓形成的风险.由于细胞色素P450酶系中起关键作用的CYP2C19酶存在基因多态性,使部分患者产生氯吡格雷低反应性即氯吡格雷抵抗.血小板聚集率高,抗血小板作用减弱,增加了不良心血管事件发生率.本文通过对氯毗格雷低反应的患者进行基因多态性分析,指导个体化用药.     

基于血小板途径的抗血栓机制的研究

血液栓塞是心血管疾病发生的重要病理过程。血栓形成离不开血小板的参与,血小板在止血和动脉血栓形成中扮演重要角色。常见的血小板活化诱导途径有二磷酸腺苷途径、花生四烯酸途径、凝血酶途径、胶原途径和血小板活化因子途径。该文针对这5 种血小板活化机制、活化途径治疗药物以及新型靶点的抗血小板药物进行综述,为血液栓塞的研究和治疗提供一定参考。     

血小板聚集功能试验在冠心病抗血小板治疗监测中的应用

目的探讨冠心病患者在用药前后血小板最大聚集率变化,以指导临床用药。方法将120例冠心病患者分成3组：阿司匹林组、氯吡格雷组和联合用药组,分别接受阿司匹林、氯吡格雷以及两者联合治疗。用药前后测定其血小板最大聚集率。结果阿司匹林组与正常对照组及用药前比,花生四烯酸诱导途径诱导的血小板最大聚集率存在显著差异（P〈0.01）;氯吡格雷组二磷酸腺苷诱导途径存在显著差异（P〈0.01）;而两者联合用药组4种诱导途径均存在明显差异（P〈0.05）。结论阿司匹林或氯吡格雷仅可抑制单一途径诱导的血小板聚集,而联合用药对4个途径均有抑制作用,用药过程中进行监测可指导用药。     

双联抗血小板联合质子泵抑制剂治疗急性心肌梗死对患者预后的影响

目的 探讨急性心肌梗死(AMI)应用双联抗血小板联合质子泵抑制剂(PPI)治疗对患者预后的影响.方法 选择原广州军区总医院心内科及我院综合内科于2014年1月至2016年6月期间收治的468例AMI患者为研究对象,根据随机数表法分为A、B、C三组,每组156例,所有患者均接受经皮冠状动脉介入(PCI)支架置入治疗,术后接受阿司匹林+氯吡格雷双联抗血小板治疗,A组不应用PPI,B组应用奥美拉唑,C组应用埃索美拉唑治疗,疗程6个月.比较治疗后三组患者主要不良心血管事件(MACE)、上消化道出血及支架内血栓形成情况.结果 A、B、C三组患者的MACE及支架内血栓形成发生率分别为9.63%和1.92%、15.38%和5.13%、13.46%和3.21%,两两比较差异均无统计学意义(P>0.05);B组和C组上消化道出血的发生率分别为3.85%和1.92%,明显低于A组的9.63%,差异均有统计学意义(P<0.05).结论 PCI术后双联抗血小板治疗过程中,加用奥美拉唑或埃索美拉唑均可有效预防上消化道出血的发生,且不增加心血管事件的发生风险.     

植入冠脉支架患者择期非心脏手术的围术期抗血小板治疗方案探究

植入冠脉支架患者正在逐渐成为接受择期非心脏手术(non-cardiac surgery,NCS)的患者中不可忽视的一个群体.既往心脏疾病、冠脉支架以及抗血小板药物使这类患者在围术期面临着血栓形成和出血的双重风险.制定适宜的围术期抗血小板治疗方案将有助于降低风险,保障患者安全.本文将围绕目前支架患者择期NCS围术期抗血小...     

西洛他唑对冠心病患者阿司匹林抵抗的干预作用

目的 观察西洛他唑(CS)对冠心病(CHD)患者阿司匹林抵抗(AR)的影响.方法 165例冠心病患者按照是否合并糖尿病(DM)分为A组:冠心病组,B组:冠心病合并糖尿病组.两组患者均口服阿司匹林(ASA)0.1g, qd, 1周后测定二磷酸腺苷(ADP)及花生四烯酸(AA)诱导的血小板聚集率(PAG).随后将A、B两组患者分别随机分成A1、A2、B1、B2四组.A1、B1两组继续服用阿司匹林0.1qd, A2、B2组加用西洛他唑50mgbid,1周后复查PAG,比较各组PAG和AR的发生情况并进行统计分析.结果 A组PAG及AR发生率较8组低(P<0.01).A1组PAG及AR与A组无明显差异(P>0.05);A2组PAG及AR较A组A1组有明显差异(P<0.01);B1组PAG及AR较B组无明显差异(P>0.05);B2组PAG及AR较B组及B1组有明显降低(P<0.01);A2组PAG及AR与B2组有统计学差异(P<0.05).结论 合并糖尿病的冠心病患者血小板聚集率及阿司匹林抵抗的发生率高于单纯冠心病患者;阿司匹林联合西洛他唑可进一步降低冠心病患者血小板聚集率,减少阿司匹林抵抗的发生,合并糖尿病的冠心病患者获益更大.     

冠状动脉支架内二次血栓形成的原因分析

目的:探讨冠状动脉支架内二次血栓形成(ST)的相关因素、预后及预防措施。方法:对我院2000年3月～2009年12月3854例行冠状动脉介入治疗(PCI)中4例二次血栓形成病人的临床特征、冠状动脉造影及支架置入情况、预后及预防措施等进行回顾性分析。结果:3854例者行冠状动脉支架治疗,4例病人发生二次血栓形成(0.1%),均为急性冠脉综合征病人。其中,男女各2人,吸烟史2例,合并糖尿病3例,高脂血症3例,高血压2例。血栓相关血管累及前降支近段4例,累及右冠状动脉近段1例(1例患者为2个支架内均有血栓形成)。最终造影显示TIMI血流达3级3例。停用波立维1例,血小板聚集率明显增高1例。结论:二次血栓防治策略是积极控制危险因素、治疗原发病、充分的预扩张、血管内超声的应用、应用高压球囊使支架贴壁良好及合理的使用抗血小板药物。     

替格瑞洛在氯吡格雷抵抗的急性冠脉综合征中疗效的初步观察

目的：观察第三代抗血小板新药血小板二磷酸腺苷（ADP）受体P2Y12拮抗剂---替格瑞洛在氯吡格雷抵抗的急性冠脉综合征（ACS）患者中的临床疗效。方法随机选取拟行冠脉内支架植入（PCI）术的ACS患者66例,PCI术前均服用氯吡格雷（300～600 mg负荷量）,服药后24 h内,应用血栓弹力图检测血小板抑制率分为两组：（1）血小板抑制率＜31％,明显减低,为氯吡格雷抵抗组6例;（2）血小板抑制率＞50％,正常,为正常组60例。两组血小板抑制率有明显差异（P＜0．001）。氯吡格雷抵抗组予替格瑞洛口服,首服180 mg,继90 mg 2次/d持续1年,替换氯吡格雷;正常组予氯吡格雷口服75 mg 1次/d持续1年。结果氯吡格雷抵抗组用替格瑞洛治疗,血小板抑制率恢复正常,且略高于正常组,两组血小板抑制率无明显差异（ P＞0．05）。 PCI术后无急性及亚急性冠脉及支架内血栓形成,无出血率增加。结论替格瑞洛对氯吡格雷抵抗者抑制急性及亚急性血栓形成有效,可显著降低ACS患者心血管事件发生率,不增加大出血。     

血小板活化功能与冠心病的关系

血小板活化在冠心病的发生、发展过程中发挥着重要作用。活化的血小板通过其表达和释放的内容物而发挥其黏附、变形、聚集和释放等病理生理作用。通过研究血小板活化功能和冠心病的关系,检测血小板活化功能,有利于心血管事件的预报和预防,同时也可以为临床合理应用抗血小板药物提供依据,从而减少急性心血管事件的发生。