常用血小板功能检测方法研究进展

血小板聚集形成血栓是急性冠状动脉综合征和经皮冠状动脉介入(PCI)治疗术后发生不良心血管事件的基本原因,抗血小板治疗是防治冠状动脉粥样硬化性心脏病(冠心病)的基石。然而,同一种抗血小板药物在不同个体可产生不同的抗血小板效应,抗血小板药物低反应者血栓事件可能增加,而抗血小板药物高反应者出血风险加大。因此,通过检测血小板功能以预测患者不良心血管事件的风险及评估出血风险有着重要的临床意义。     

CYP2C19基因型指导下的抗血小板治疗在CABG术后的应用进展

冠状动脉旁路移植术后的抗血小板治疗是重要的药物治疗之一,它在改善患者桥血管通畅率以及减少患者术后主要心血管不良事件（MACE）发生发挥着积极的作用。临床上发现一些患者对常用的抗血小板药物氯吡格雷存在抵抗,导致术后桥血管狭窄及MACE事件的发生率增高,这种抵抗可能与细胞色素P450 2C19（CYP2C19）基因多态性有关。而第三代P2Y12受体拮抗剂的抗血小板效果不受CYP2C19基因型的影响。有专家共识推荐进行CYP2C19基因型检测来确定双抗治疗方案,那么依据CYP2C19基因型检测的个体化治疗方案是否可以降低患者术后的主要心血管不良事件的发生率？本文将从氯吡格雷抵抗与CYP2C19基因型的关系、冠状动脉旁路移植术后抗血小板治疗现状及现有专家共识推荐等几方面进行回顾与分析。     

阿司匹林抵抗

阿司匹林在预防和治疗血栓栓塞性疾病方面，已经作为常规药物广泛应用。然而患者服用阿司匹林后并不能获得均一的抗血小板效果，存在明显的个体差异，有部分患者对阿司匹林的心血管保护作用存在抵抗现象（Aspirin Resistance，AR），仍会发生心血管血栓事件。近年来阿司匹林抵抗问题越来越受到重视。以下从阿司匹林的发展历史，阿司匹林抵抗的定义、分类、发生机制以及对策等方面作一综述。     

替格瑞洛改善氯吡格雷抵抗急性心肌梗死患者治疗的疗效及价值分析

目的:观察替格瑞洛对改善氯吡格雷抵抗急性心肌梗死患者治疗效果的影响。方法:选择2017年1月—2018年6月我院收治的氯吡格雷抵抗急性心肌梗死患者78例,采用随机数表法分为两组,各39例。对照组口服阿司匹林肠溶片+硫酸氢氯吡格雷片,观察组口服阿司匹林肠溶片+替格瑞洛片。比较两组血小板聚集率、炎性指标及不良心血管事件发生情况。结果:观察组血小板聚集率、超敏C-反应蛋白值、P选择素值及不良心血管事件发生率均低于对照组,差异有统计学意义(P<0.05)。结论:针对氯吡格雷抵抗急性心肌梗死患者,应用替格瑞洛利于降低血小板聚集率、炎性反应,减少不良心血管事件发生。     

心肌梗死患者经皮冠状动脉介入术术后双抗血小板治疗变替格瑞洛单抗治疗的可行性分析

目的分析心肌梗死患者经皮冠状动脉介入术(PCI)后双抗血小板治疗变替格瑞洛单抗治疗的可行性。方法 2013年6月至2015年6月共收集90例心肌梗死患者为研究对象,依据随机数字表格法将患者分为两组各45例,均行PCI治疗,术后均给予阿司匹林+替格瑞洛双联抗血小板治疗,对照组双抗用药1年,观察组双抗6个月后开始慢慢减少阿司匹林应用,3个月后完全变替格瑞洛单抗治疗,共用药1年,比较2组治疗前后凝血指标、血小板聚集率、不良心血管事件及出血事件。结果与治疗前比较,2组治疗1年PT、aPTT明显延长,血小板聚集率明显下降,差异有统计学意义(P0.05);2组不良心血管事件及出血事件比较差异无统计学意义(P0.05)。结论心肌梗死患者PCI术后阿司匹林+替格瑞洛双联抗血小板治疗6个月变替格瑞洛单抗用药至1年相比双联1年在抑制血小板聚集方面作用类似,但变替格瑞洛单抗治疗能有效减少出血发生,且不显著增加不良心血管事件。     

双联抗血小板治疗在冠状动脉旁路移植术后的应用进展

目前,联合阿司匹林和P2Y12抑制剂的双联抗血小板方案已广泛应用于冠状动脉旁路移植术(CABG)后患者,其中P2Y12抑制剂可以有效增强阿司匹林对血小板聚集的抑制作用,降低阿司匹林抵抗率。但是,双联抗血小板的应用可能会增加出血风险,且有约10%的患者在随访过程中会发生显著心脑血管不良事件,故单纯的抗血小板治疗似乎不能有效防止术后血栓形成。术后应用双联抗血小板方案的治疗时间目前尚未统一。随着新型口服抗凝药的不断进展,未来新型口服抗凝药联合抗血小板治疗可能是改善CABG后患者结局的新方法。     

MPV和AR与非ST段抬高ACS患者不良预后的相关性

目的探讨平均血小板体积（MPV）和阿司匹林抵抗（AR）与非sT段抬高的急性冠脉综合征（ACS）患者不良心血管事件发生的相关性。方法197例非sT段抬高的ACS患者,每日口服阿司匹林100mg〉4周,检测由ADP诱导的血小板聚集率（PAG）和Sysmex XT-1800i检测的MPV,根据PAG和MPV将患者分为4组：①MPV正常不伴阿司匹林抵抗组（对照组）;②MPV正常伴阿司匹林抵抗组;③MPV升高不伴阿司匹林抵抗组;④MPV升高伴阿司匹林抵抗组,随访观察4组主要不良事件（心源性死亡、心肌梗死、血运重建）发生的比率并进行比较。结果在197例非ST段抬高的ACS患者中,4组不良事件发生率分别为12．0％、18．6％、23．4％和62．5％,其中组4（MPV升高伴阿司匹林抵抗组）与组1（对照组）比较,不良事件发生比率明显增高（62．5％VS12．0％,P〈0．0001）。结论MPV升高和AR与非sT段抬高的ACS患者不良心血管事件的发生呈正相关．它是非ST段抬高的ACS患者的重要危险因素和独立预测因子。     

抗血小板抵抗的实验室检测

<正>口服抗血小板药物是心血管动脉粥样硬化疾病现代药物治疗中的一个奠基石。阿司匹林/氯吡格雷降低血管疾病患者不良事件发生风险的效力,在过去的20年里已经得到很好的认可,其在缺血性心脑血管疾病的一、二级预防中可使该事件如心肌梗死、卒中的发生率降低25%,冠状动脉搭桥及动脉栓塞事件降低48%,肺栓塞降低67%,深静脉血栓形成     

氯吡格雷抵抗研究进展

氯吡格雷作为一种抗血小板聚集药物,在急性冠脉综合征和经皮冠状动脉介入治疗前后发挥着重要作用。然而,血小板对氯吡格雷的反应在个体间具有很大差异,氯吡格雷抵抗是指血小板对氯吡格雷低反应或无反应,同时,氯吡格雷抵抗与心血管事件的发生有密切的关系。目前,对于氯吡格雷抵抗患者的抗血小板聚集治疗国内外尚无统一的方案,该文就氯吡格雷抵抗的定义、机制以及氯吡格雷抵抗患者的治疗策略予以综述。     

阿司匹林抵抗：从实验室到临床

抗血小板药物在对心脑血管事件的防治上起着关键作用,其中以阿司匹林应用最为广泛。但有研究报道40%的患者,其血小板功能未能被阿斯匹林抑制[1],同时这种药物低反应又与心血管事件密切相关[2]。阿司匹林不能充分抑制血小板聚集（生物学抵抗）,     

低剂量替格瑞洛治疗稳定型冠心病患者的疗效及安全性评价

 目的  评价低剂量替格瑞洛治疗稳定型冠心病 （stable coronary artery disease,SCAD）患者的疗效及安全性。方法  采用随机平行对照的方法入选SCAD患者413例,分别给予替格瑞洛60 mg/次、2次/日 (n=192)或氯吡格雷50 mg/次、1次/日 (n=221),两组均联合应用阿司匹林100 mg/次、1次/日,疗程12个月。采用3种检测方法多时点评价两组患者的血小板功能;比较两组患者的心血管死亡、非致死性心肌梗死、卒中等主要不良心脑血管事件及出血事件发生率。结果  替格瑞洛组在各时点的血小板高反应性发生率均低于氯吡格雷组,差异有统计学意义;替格瑞洛组较氯吡格雷组主要不良心脑血管事件发生率显著降低,差异有统计学意义 (5.2% vs. 11.7%,HR＝0.412,95%CI为0.193～0.878,P＝0.022);替格瑞洛组出血事件发生率高于氯吡格雷组,但差异无统计学意义。结论  低剂量替格瑞洛抗血小板方案可以降低SCAD患者主要不良心脑血管事件发生率。     

CTA判断冠状动脉粥样硬化对非心脏手术计划的影响及预测围手术期心脏风险事件的价值分析

目的探讨CT冠状动脉造影(CTA)检查对于非心脏手术患者手术计划的影响及预测患者围手术期出现不良心血管事件的价值。方法选取在本院接受非心脏手术治疗且术前怀疑或已经确诊冠状动脉粥样硬化的患者116例,患者术前均进行CTA检查,根据患者是否进行如期手术分组,并探讨CTA检查结果对患者如其手术的影响作用,统计分析患者围手术期不良心血管事件发生率。结果本研究83例如期手术患者中,围手术期均未见严重的心血管不良事件发生,仅4例患者出现心动过速,未经特殊处理后自行恢复;比较如期手术组、推迟或放弃手术组患者的年龄、性别、吸烟史、BMI、合并疾病情况、心率比较差异均无统计学意义(P0.05);冠脉中度、重度狭窄患者的如期手术率显著的低于轻度狭窄患者(P0.05);冠脉重度狭窄患者的如期手术率显著的低于中度狭窄的患者(P0.05);2支、3支冠脉狭窄患者的如期手术率显著的低于单支狭窄患者(P0.05);3支冠脉狭窄患者的如期手术率显著的2支冠脉狭窄的患者(P0.05)。结论对于非心脏手术患者,冠脉病变及其严重程度会对患者的手术计划产生影响,对于怀疑或确诊冠心病患者术前进行CTA检查并进行手术耐受评估具有较为重要的临床价值。     

Antiplatelet effect of aspirin in patients with coronary artery disease

Cardiovascular disease is the number one cause of death globally, and atherothrombosis is the underlying cause of most cardiovascular events. Several studies have shown that antiplatelet therapy, including aspirin (acetylsalicylic acid), reduces the risk of cardiovascular events and death. However, it is well-known that many patients experience cardiovascular events despite treatment with aspirin, often termed "aspirin low-responsiveness". This fact has caused considerable debate: does biochemical aspirin low-responsiveness have prognostic value? Can low-responders be reliably identified? And if so, should antithrombotic treatment be changed? Is the whole discussion of antiplatelet drug response merely a result of low compliance? Compliance should be carefully optimised, before evaluating the pharmacological effect of a drug. It is well-known that cardiovascular disease is multifactorial, and, therefore, total risk reduction is not feasible. Aetiological factors to the variable platelet inhibition by aspirin seem to include genetic factors, pharmacological interactions, smoking, diabetes mellitus, and increased platelet turnover. It is a captivating thought that antiplatelet therapy may be improved by individually tailored therapy based on platelet function testing. Ongoing studies are challenging the current one-size-fits-all dosing strategy, but the preceding evaluation of platelet function assays has not been adequate. The overall objective of this thesis was to evaluate the reproducibility of and aggreement between a number of widely used platelet function tests and to explore the importance of platelet turnover for the antiplatelet effect of aspirin in patients with coronary artery disease. In the intervention studies (studies 1, 3, and 4), optimal compliance was confirmed by measurements of serum thromboxane, which is the most sensitive assay to confirm compliance with aspirin. In study 1, platelet function tests widely used to measure the antiplatelet effect of aspirin were evaluated in healthy individuals and patients with coronary artery disease. Pharmaco-specific metabolites were measured in urine and serum to investigate the pharmacodynamic effect of aspirin and to enable the comparison with the more global tests of platelet function. Based on repeated duplicate measurements, we evaluated the reproducibility of each test. We found that reproducibility of the classical reference method was not impressive and that the newer, so-called point-of-care tests differed markedly on reproducibility. With coefficients of variation of about 3%, the VerifyNow Aspirin test was clearly the most reproducible test - even after correction of the official scale, which begins at about 350 aspirin reaction units and, therefore, results in artificially low coefficients of variation. Among the platelet function tests investigated, Multiplate was most sensitive for aspirin treatment. In study 2 we performed the hitherto largest study of newly released, immature platelets as a marker of platelet turnover. The study population included healthy individuals, patients with stable coronary artery disease, and patients with acute coronary syndromes. The main finding was an increased fraction of immature platelets in patients with ST-segment myocardial infarction, indicating an increased platelet turnover. Smoking and type 2 diabetes were identified as independent determinants of platelet turnover. In study 3 we explored the relationship between platelet turnover and the antiplatelet effect of aspirin in patients with stable coronary artery disease. The study results support the hypothesis that an increased platelet turnover reduces the antiplatelet effect of aspirin. The main findings were: 1) platelet turnover correlated with platelet aggregation measured by Multiplate and with sP-selectin, a marker of platelet activation. 2) Patients with diabetes mellitus type 2 had reduced antiplatelet effect of aspirin compared with patients without diabetes. 3) Widely used platelet function tests differ with respect to dependence on platelet parameters, including platelet count. 4) Smoking, diabetes mellitus type 2, and thrombopoietin were identified as independent determinants of platelet turnover. 5) The relative fraction of immature platelets has been employed in most previous studies, but in stable patients the absolute immature platelet count does not seem dependent on the total platelet count, and it has a stronger correlation with both platelet activation measured by sP-selectin and with platelet aggregation during treatment with aspirin. In study 4 we investigated platelet turnover and the antiplatelet effect of aspirin in a nested case-control study on patients with previous definite stent thrombosis. Patients with stent thrombosis were compared with patients without stent thrombosis, with whom they were matched at a 1:2 ratio with respect to risk factors for stent thrombosis: age, sex, stent type, and indication for percutaneous coronary intervention. The study showed that patients with previous stent thrombosis have reduced antiplatelet effect of aspirin and a tendency towards increased platelet turnover. In conclusion, widely used platelet function tests markedly differ on reproducibility, and the agreement between tests is relatively poor. An increased platelet turnover as suggested by the presence of newly formed immature platelets is important for the antiplatelet effect of aspirin, and, perhaps also for the development of acute coronary thrombosis. In the future, individually tailored antiplatelet therapy may potentially improve the benefit-risk ratio of antiplatelet therapy.     

Antiplatelet drugs

Antiplatelet drugs protect against myocardial infarction, stroke, cardiovascular death and other serious vascular events in patients with a history of previous vascular events or known risk factors for cardiovascular disease. Aspirin reduces the risk of serious vascular events in patients at high risk of such an event by about a quarter and is recommended as the first-line antiplatelet drug. Clopidogrel reduces the risk of serious vascular events among high-risk patients by about 10% compared with aspirin. It is as safe as aspirin, but much more expensive. It is an appropriate alternative to aspirin for long-term secondary prevention in patients who cannot tolerate aspirin, have experienced a recurrent vascular event while taking aspirin, or are at very high risk of a vascular event (>/= 20% per year). Addition of clopidogrel to aspirin reduces the risk of serious vascular events among patients with non-ST-segment elevation acute coronary syndromes by 20%, and patients undergoing percutaneous coronary intervention by 30%, compared with aspirin alone. Addition of a glycoprotein IIb/IIIa receptor antagonist to aspirin reduces the risk of vascular events among patients with non-ST-segment elevation acute coronary syndromes by 10% and among patients undergoing percutaneous coronary intervention by 30%, compared with aspirin alone; it appears to provide incremental benefit in patients also treated with clopidogrel. Addition of dipyridamole to aspirin seems to be more effective than aspirin alone for preventing recurrent stroke, but its overall effect in preventing serious vascular events in patients with ischaemic stroke and transient ischaemic attack has not been determined.     

氯吡格雷对急性冠脉综合征患者阿司匹林抵抗的影响

目的观察氯吡格雷对急性冠脉综合征（ACS）患者阿司匹林抵抗的影响。方法回顾性分析40例我科2005年6月至2006年9月确诊为ACS并采取阿司匹林联合氯吡格雷治疗患者（治疗组）的临床资料,与40例我科2004年1月至2005年1月期间确诊为ACS采取单纯阿司匹林治疗患者（对照组）的临床资料进行比较,两组患者基本资料无显著性差异,比较两组患者二磷酸腺苷（ADP）和花生四烯酸（AA）诱导的血小板聚集率及阿司匹林抵抗（AR）发生情况。结果治疗组两种诱导剂诱导的血小板平均聚集率与对照组相比均明显下降（P〈0.0 5）,且治疗组AR发生率显著低于对照组（P〈0.05）,差异有统计学意义。结论 ACS在采用阿司匹林抗血小板功能的同时,加用氯吡格雷可明显降低患者发生阿司匹林抵抗,更有效的减少了不良心血管事件的发生。     

Combined use of extended-release niacin and atorvastatin: safety and effects on lipid modification

Background Cholesterol-lowering therapy with statins has been reported to reduce the morbidity and mortality of cardiovascular diseases. This study aimed to investigate the effects of combined application of extended-release niacin and atorvastatin on lipid profile modification and the risks of adverse events in patients with coronary artery disease. Methods Consecutive 108 patients with coronary artery disease and serum total cholesterol （TC） 〉 3.5 mmol/L were randomized into two groups： group A using atorvastatin and group B using extended-release niacin （niacin ER） and atorvastatin. Plasma lipid profile, glucose, and adverse events were assessed at the hospitalization, and 6 and 12 months after treatment. In addition, clinical cardiovascular events were evaluated after 12 months of treatment. Results The levels of TC, low density lipoprotein cholesterol （LDL-C） were significantly decreased （P 〈0.05） in groups A and B, but the levels of high density lipoprotein cholesterol （HDL-C） and ApoA increased by 29.36% and 40.81% respectively after 12 months of treatment in group B （P 〈0.01）. The medications were generally well tolerated in the two groups. No significant difference of adverse events was found between the two groups （group A： 3.2% vs group B 5.1%, P 〉0.05）. Conclusions Combined use of extended-release niacin with atorvastatin was superior to atorvastatin monotherapy alone in lipid profile regulation. Combination therapy with niacin ER and atorvastatin was well tolerated and safe in patients with coronary artery disease.     

经桡动脉的旋磨治疗26例冠心病严重钙化

【目的】探讨经桡动脉冠状动脉旋磨术治疗冠状动脉钙化病变的安全性及有效性。【方法】回顾性分析26例经桡动脉冠状动脉旋磨术的冠心病患者的临床资料、旋磨参数、手术结果和随访术后6个月主要不良心血管事件(包括死亡、心肌梗死、靶病变血运重建)。【结果】26例患者选择6F/7F指引导管的比例分别是14/12例,其中25例患者行单只血管的旋磨治疗,1例患者同时行前降支和回旋支旋磨治疗,管腔狭窄由术前85%±11%减少至52%±8%,全部患者手术成功,术中无死亡、心肌梗死和冠脉穿孔等并发症发生,术后桡动脉闭塞发生率30.7%,6个月随访总不良心血管事件11.5%。【结论】经桡动脉旋磨治疗手术成功率高,不良心血管事件发生率低,临床安全、有效,可以推广。     

超敏肌钙蛋白T对急性冠状动脉综合征的临床诊断及短期预后价值

目的探讨血清超敏肌钙蛋白T(hs-TnT)对急性冠状动脉综合征(ACS)患者的临床诊断及短期预后价值。方法选择2010年1月～2011年6月本院收治的急性冠状动脉综合征患者186例,所有患者入院后24 h内做血清hs-TnT检测及常规TnT检测,住院期间做冠状动脉造影,比较hs-TnT及常规TnT检测对心肌坏死的检出率,分析hs-TnT水平与冠状动脉病变程度及范围的关系。随访1～2个月,记录其主要心血管不良事件。结果血清hs-TnT检测心肌坏死检出率为52.69%,高于常规TnT的检出率(32.26%)(P<0.05);血清hs-TnT水平随冠状动脉狭窄的严重程度及范围的扩大而升高(P<0.05),对冠状动脉病变程度及范围具有临床指导意义。随访1～2个月,hs-TnT升高组患者的主要心血管不良事件发生率高于hs-TnT正常组(P<0.05)。结论hs-TnT对急性冠状动脉综合征患者的临床诊断及短期预后价值优于常规TnT检测,对冠状动脉病变程度及范围具有临床指导意义,值得临床推广应用。