PCI术后双联抗血小板治疗并自发纵膈血肿1例

<正>双联抗血小板治疗(DAPT)已经成为经皮冠状动脉介入治疗(PCI)术后标准治疗,无论是单纯球囊扩张、植入金属裸支架(BMS)还是药物洗脱支架(DES),DAPT均已被证实可减少支架内血栓形成、心肌梗死和死亡风险。新型抗血小板药物替格瑞洛因其作用直接、有效,被各大指南推荐为首选DAPT药物之一,临床应用广泛,但其临床可能引起自发出     

血小板检查方法以及临床意义

目的 探讨血小板功能检测对于临床相关疾病的诊断和抗血小板药物的筛选及相关研究有着重要的意义.目前,血小板功能检测的实验与方法日益增多,但所有这些检测方法均有不足之处,因而有必要研究和发展一种操作简便、检测灵敏度高的方法.对近年来血小板功能检测方法诸如血小板的一般功能检测、血小板黏附功能测定、血小板聚集功能测定、血小板释放功能测定、血小板凝血活性检测和流式细胞术在血小板功能检测中的应用等研究进展进行了综述,并对研究前景作了简单的展望.     

冠心病介入治疗患者个体化抗血小板治疗进展

冠心病已成为威胁我国人民身体健康的重大心血管疾病之一。经皮冠状动脉支架植入术是治疗严重冠心病的重要方法,为了减少术后支架内血栓事件的发生率,术后服用双联抗血小板药物得到了各国指南推介。氯吡格雷是最常用的双联抗血小板药物之一,但研究显示,部分患者服用氯吡格雷后,仍有较高的支架内血栓发生率,即存在血小板抵抗(high on-treatment platelet reactivity,HTPR)。对于这部分患者,增加氯吡格雷剂量或改换药物能否改善HTPR,目前研究结果仍有争议。本文从HTPR的筛查方法、新型抗血小板药物的应用以及预后等方面对该问题进行综述。     

抗血小板药物在冠状动脉内支架植入术前的应用

由冠脉阻塞所致的缺血型心脏病在临床上较为常见，经皮冠状动脉腔内成型术（PTCA）是冠心病的主要治疗手段之一，冠状动脉内支架植入术是在PTCA基础上发展起来的一个介入技术，其应用在很大程度上提高了介入技术对于血管病变的临床价值。但无论是PTCA还是冠状动脉内支架植入术均面临着急性血管闭塞和再狭窄难题，特别是冠状动脉腔内治疗术能显著激活血小板而增加了急性期或亚急性期血栓形成的风险，目前主要预防措施是应用抗血小板和抗凝药物治疗，以减少血栓形成，本文主要针对抗血小板药物在药理学预防血栓形成的疗效以及副作用的研究现状做一综述。     

抗血小板药物临床应用概述

抗血小板药物又称血小板功能抑制剂,60年代已在临床应用,当时将该类药归属于抗凝疗法范畴.随着对血栓性疾病发生机理的认识,抗血小板治疗在临床中的地位愈来愈重要,新的血小板功能抑制剂不断涌现,抗血小板药物已成为单独的一类药物在血栓性疾病中得到广泛的应用.本文就抗血小板药物的临床应用作一简要综述.     

支架植入术后缺血事件和双联抗血小板治疗后出血事件风险评估的研究进展

随着我国冠状动脉粥样硬化性心脏病患病人数的迅速增长和介入治疗技术的不断改良,越来越多的患者接受了药物洗脱支架植入术。双联抗血小板治疗可以降低术后支架内血栓形成发生风险,同时也增加了出血事件的发生风险。相关指南建议医生个性化制定双联抗血小板治疗疗程。日常治疗决策过程中,制定特定患者双联抗血小板治疗最佳疗程前需对其出血事件和缺血事件发生风险进行评估。近年来,不断有学者对支架植入术后接受双联抗血小板治疗患者的临床特征进行汇总分析,基于分析结果开发支架植入术后缺血事件和双联抗血小板治疗出血事件发生风险评估工具。本文主要就已发表的高质量风险评估工具进行综述,旨在为临床医生的后期应用与研究提供帮助。     

破裂动脉瘤支架辅助栓塞中抗血小板药物和抗凝药物的使用分析

目的探讨抗血小板药物与抗凝药物在破裂动脉瘤的支架辅助栓塞中的应用价值。方法选择2014年3月‐2015年3月该院收治的破裂动脉瘤合并蛛网膜下腔出血并经临床证实行支架置入栓塞术治疗的患者50例,采用阿司匹林肠溶片、氯吡格雷片抗血小板药物以及低分子肝素抗凝药物进行治疗,比较分析治疗前与治疗后的效果。结果该研究50例患者治疗前与治疗后的血常规与凝血功能指标比较差异无统计学意义(P0.05);治疗前功能缺失率为100%,治疗6个月后功能缺失率为2%,治疗前与治疗后功能缺失率比较差异有统计学意义(P0.01)。结论将阿司匹林肠溶片、氯吡格雷片抗血小板药物和低分子肝素抗凝药物用于破裂动脉瘤的支架辅助栓塞治疗中可以明显改善临床症状,促进患者神经功能的恢复,值得推广与应用。     

抗血小板药物的临床应用

目的：总结抗血小板药物的临床治疗效果。方法：综合抗血小板药物在预防治疗动脉栓塞的研究现状。结果：心脑血管病患者要应用抗血小板药物进行预防治疗。结论：心脑血管病患者中高危人群应用抗血小板药物治疗对其预后具有重要影响。     

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。     

不同中药在抗血小板药物抵抗患者中的研究

阿司匹林和氯吡格雷双联抗血小板聚合药物是冠心病治疗的基石,近年来,抗血小板药物抵抗的发生率逐年增高,在临床上也缺乏安全有效的治疗手段。研究发现,活血化瘀中药(单味药:银杏、三七,中成药:复方丹参滴丸、通心络、血塞通等)具有改善抗血小板药物抵抗程度、增加抗血小板药物敏感性的作用,在临床治疗抗血小板药物抵抗患者中体现出了一定的优势。     

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.     

急性冠脉综合征介入术患者抗血小板药物治疗后血小板聚集率的比较

目的观察冠脉介入术患者抗血小板药物治疗后血小板聚集率的变化,评估抗血小板治疗的疗效和安全性。方法将96例急性冠脉综合征（ACS）患者随机分为三联组（加用替罗非班）和双联组,所有患者均正规使用肝素、盐酸氯吡格雷、阿司匹林,观察两组血小板聚集率、出血并发症、血小板计数、5d内复合终点事件。结果血小板聚集率三联组明显下降（36.21%与45.74%比较,P〈0.05）,出血并发症比双联组有增多趋势,但无统计学意义（5.3%vs 2.6%）;5d复合终点事件发生率三联组低于双联组（1.8%vs 2.6%）,但差异无统计学意义。结论冠状动脉介入术后检测血小板聚集率,有助于合理安全地使用抗血小板药物。     

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.

     

急性冠状动脉综合征患者抗血小板药物抵抗的影响因素分析

目的 探索分析急性冠状动脉综合征患者抗血小板药物抵抗的临床影响因素,以帮助临床医师快速识别出可能存在抗血小板药物氯吡格雷抵抗的患者。方法 本研究纳入2013年全年在中国医学科学院阜外医院行冠状动脉介入术的急性冠状动脉综合征患者。依据血栓弹力图二磷酸腺苷诱导的血小板纤维蛋白凝块强度(adenosine diphosphate-induced platelet-fibrin clot strength,MA_ADP),将入选患者分为药物抵抗组 (MA_ADP>47 mm) 与非药物抵抗组(MA_ADP≤47 mm)。利用临床基线数据,采用单因素和多因素Logistic 回归分析筛选出与抗血小板药物氯吡格雷抵抗独立相关的影响因素。结果 共2 511例患者被纳入本研究,其中有781例(31.10%)患者存在氯吡格雷治疗下的药物抵抗。通过单因素分析及进一步的多因素Logistic 回归分析,共筛选出肾功能异常(OR=3.08,95%CI:1.28~7.36)、女性(OR=2.86,95%CI:2.26~3.61)、合并糖尿病(OR=1.61,95%CI:1.33~1.95)、血小板增多(OR=1.55,95%CI:1.07~2.25)及质子泵抑制剂的使用(OR=1.25,95%CI:1.02~1.54)等5个与抗血小板药物抵抗有关的临床因素。结论 肾功能异常、女性、合并糖尿病、血小板增多、使用质子泵抑制剂是患者发生抗血小板药物氯吡格雷抵抗的独立影响因素,在临床诊疗过程中需予以重点关注,从而指导个体化抗血小板治疗。     

非ST段抬高型急性冠状动脉综合征抗栓治疗进展

非ST段抬高型急性冠状动脉综合征的治疗包括药物治疗、经皮腔内冠状动脉介入治疗和冠状动脉旁路移植术,而抗栓药物治疗大大减少了患者的病死率、心肌梗死发生率及致残率,同时提高患者生活质量。抗栓药物包括抗血小板和抗凝药。其中抗血小板药有阿司匹林、磷酸腺苷受体拮抗剂和血小板膜糖蛋白抗体拮抗剂等;抗凝药有普通肝素和低分子肝素、抗Ⅹa因子抑制药和直接凝血酶抑制剂等。     

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。     

动脉粥样硬化高危人群中阿司匹林抵抗调查分析

目的调查社区动脉粥样硬化高危人群中阿司匹林抵抗(AR)或半抵抗(ASR)的发生率及其流行病学特征,并探讨其与危险因素的相关性。方法筛选200例动脉粥样硬化高危患者服用阿司匹林(100mg/d)至少7天以上,用二磷酸腺苷(ADP)和花生四烯酸(AA)作诱导剂测定其前后血小板聚集功能变化及血清血栓烷B2(TXB2)水平测定。结果200例动脉粥样硬化高危人群中AR发生率为4.5%,ASR者占20.7%。血清TXB2,AA、ADP诱导的血小板聚集率与健康对照组相比有显著统计学差异(P<0.01);血清TXB2与血小板聚集率有较好的相关性(r=0.871)。结论社区动脉粥样硬化高危人群服用阿司匹林后部分产生AR或ASR;AR或ASR人群发生冠心病事件的风险高于阿司匹林敏感(AS)人群;检测AA、ADP诱导的血小板聚集率,血清TXB2可作为动脉粥样硬化高危人群发生AR或ASR的评价指标。     

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.     

三联抗血小板治疗在氯吡格雷抵抗患者行冠脉介入治疗中的疗效与安全性研究

目的本研究通过观察经皮冠状动脉介入术（PCI）患者血管舒张剂刺激磷蛋白（VASP）磷酸化（VASP-P）程度、血小板α颗粒糖蛋白（CD62P）的变化规律,探讨三联抗血小板治疗在氯吡格雷抵抗患者（Clopidogrel resistance,CR）行PCI治疗中的疗效与安全性。方法选择行冠状动脉支架术的患者201例,随机分为标准组（n=100）及优化组（n=100）。标准组给予标准抗血小板治疗,优化组患者术中给予替罗非班持续泵入36～72 h,其后氯吡格雷改为150 mg/d。另外选择30例健康者作为正常对照组。观察VASP-P、CD62P、血小板反应性指数（PRI）及住院期间主要心血管不良事件（MACE）及出血发生率等指标。结果标准组及优化组CR患者药物治疗后的CD62P和PRI均较治疗前明显下降,差异均有统计学意义（均P〈0.05）;优化组CR患者PCI术后36 h的CD62P和PRI较术前显著降低,差异均有统计学意义（均P〈0.05）。患者PCI术后住院期间主要心血管事件（MACE）发生率,优化组低于标准组,差异有统计学意义（P〈0.05）;出血发生率两组比较差异无统计学意义（P〉0.05）。结论在两联抗血小板治疗基础上加用盐酸替罗非班可进一步抑制患者的血小板聚集功能。     

PTCA及血管内支架术中冠脉循环血小板功能的变化

目的 探讨经皮腔内冠脉成形术（PTCA）及冠脉内支架术对冠脉循环中血小板功能的影响。方法 29例冠心病患者分成冠脉造影组（8例）和PTCA加支架组（21例）,分别于术前及术后即刻采集冠状静脉窦血,采用比浊法测定血小板最大聚集率（MPAR）,放免法测定血小板α-颗粒膜蛋白（GMP－140）及血栓素B2（TXB2）的浓度。并对PTCA及支架术中不同时间点血小板功能指标的变化情况进行了观察。结果 冠脉造影前后血小板功能指标无显著变化;PTCA及支架组在球囊预扩张即刻各血小板功能指标均轻度增高;支架后即刻显著升高（P＜0．05）,支架后10min有下降趋势。结论 冠脉造影对冠脉循环血小板功能无显著影响;PTCA及支架术中能使血小板功能激活。