不同负荷剂量氯吡格雷对血小板聚集率的影响

目的比较两种剂量氯吡格雷的起效时间及安全性,为急性冠状动脉（冠脉）综合征患者用药方案提供依据。方法60例急性冠脉综合征使用不同负荷剂量氯吡格雷患者随机分为A组（300mg）和B组（600mg）,均予氯吡格雷75mg／d后续治疗。以腺苷二磷酸（ADP）5μmol／L及20μmol／L作为诱导剂检测服药前及服药后2h和6h的血小板聚集率,并检测服药前及服药后第3天的血自细胞及血小板计数。结果在ADP20μmoL／L诱导的血小板聚集检测中,两组均显示服药后6h比服药后2h达到更高的血小板聚集抑制水平[A组（29．75±12．11）％比（43．63±14．31）％,P〈0．05;B组（28．86±10．24）％比（34．86±10．84）％,P〈0．05]。B组与A组相比,在服药后2h即起到更加明显的血小板聚集抑制作用[（34．86±10．84）％比（43．63±14．31）％,P〈0．05]。服药后3d内所有人选患者均无出血、自细胞减少及血小板减少等事件发生。结论氯吡格雷600mg作为负荷剂量较之300mg可以更快地达到较高水平的血小板抑制作用,且两者安全性相似。     

不同氯吡格雷代谢型急性心肌梗死患者的血小板聚集率变化

目的观察不同氯吡格雷代谢型急性心肌梗死患者使用氯吡格雷后血小板聚集功能的被抑制情况。方法入选2013年3—8月急性心肌梗死患者48例,经过基因检测分为氯吡格雷慢代谢型6例、快代谢型17例和中间代谢型25例。患者均于入病房前服用负荷剂量阿司匹林300 mg和氯吡格雷300 mg,之后阿司匹林100 mg/d和氯吡格雷75 mg/d连续服用,于服药后第6天检测血小板聚集率、血细胞计数、纤维蛋白原含量和肝肾功能。结果所有患者服用氯吡格雷后第6天的血小板聚集率明显下降,二磷酸腺苷、肾上腺素诱导的抑制率分别为74%和84%。氯吡格雷快代谢型、中间代谢型和慢代谢型3组急性心肌梗死患者的二磷酸腺苷诱导的血小板聚集率分别为22.2%±13.4%、32.1%±20.1%和18.6%±13.9%(P>0.05),3组血小板抑制率分别为87%、78%和82%。结论本研究中不同氯吡格雷代谢型急性心肌梗死患者的血小板聚集功能的抑制情况无明显差异。     

不同维持量氯吡格雷对ACS患者血小板聚集功能影响的观察

目的评估不同维持剂量氯吡格雷对择期PCI的ACS患者血小板聚集率的影响,探讨高维持剂量氯吡格雷对ACS患者的有效性及安全性。方法选择接受药物治疗、择期PCI的急性冠脉综合征患者150例,随机分为2组(各75例),2组均服用300mg负荷量氯吡格雷,然后分别给予氯吡格雷150mg/d、75mg/d治疗14d,14d后所有患者接受75mg/d氯吡格雷治疗直至PCI术后1年。分别于服药前、服药后第14天采2组患者静脉血,采用光学比浊法测定血小板聚集率(PA),同时计算血小板聚集抑制率(PAI)。观察住院14天内2组终点事件发生情况。结果试验组和对照组服药前血小板聚集率的差别无统计学意义(89.63±4.89vs.90.27±4.84,p>0.05);试验组服药第14天的血小板聚集率较对照组明显下降(41.36±5.13vs.51.69±3.98,p<0.05),血小板聚集抑制率较对照组明显增强(48.27±6.29vs.38.58±5.48,p<0.05),均有统计学差异。住院14天内,两组均无心血管死亡、严重的颅内出血和严重血小板减少,亚急性血栓形成发生率(1.3%vs4.0%,P>0.05)相近,轻微出血发生率(2.7%vs4.0%,P>0.05)无统计学差异。结论对高危急性冠脉综合症患者,150mg/日高氯吡格雷维持量可以明显降低血小板聚集率,从而降低血栓事件,且不增加短期出血风险,具有较好的耐受性和安全性。     

不同剂量氯吡格雷对急性冠脉综合征并肾功不全患者血小板聚集率的影响

目的：比较不同剂量氯吡格雷对急性冠脉综合征（ACS）合并肾功能不全老年患者血小板聚集率的影响。方法：81例ACS并肾功能不全老年患者被随机分成两组,两组均予阿司匹林肠溶片300mg顿服后,甲组（41例）予氯吡格雷75mg／d维持,乙组（40例）予氯吡格雷50mg／d维持。入院后24h内和第28d分别测定血小板聚集率（PAR）,肝、肾功能并统计两组主要不良心血管事件和出血发生率。结果：（1）两组年龄,性别．血小板聚集率．肝、肾功能的基础状态无显著差异（P〉0．05）;（2）甲组第28d血小板聚集率[以0．5μmol／L、1μmol／L二磷酸腺苷为诱导刺,分别为（24±15）％、（40±16）％],与基础状态（53±10）％、（75±11）％比较明显下降（P〈0．05）;乙组第28d血小板聚集率（24±14）％、（41±15）％与基础状态（52±10）％、（74±12）％相比也显著下降（P〈0．05）;但两组血小板聚集率治疗后无显著差异（P〉0．05）。两组患者在28d内共发生心血管不良事件9例,甲组4例（9．8％）,乙组5例（12．5％）,两组无显著差异（P〉0．05）;（3）轻度出血,甲组5例（12．2％）,乙组1例（2．5％）,甲组明显增加（P〈0．05）;中重度出血甲组1例,乙组0例,两组无显著差异（P〉0．05）。结论：急性冠脉综合征合并肾功能不全老年患者,服用不同剂量氯吡格雷均安全有效,低剂量（50mg／d）可减少轻度出血并发症。     

氯吡格雷对家兔血小板聚集率与创伤性出血的影响

目的观察氯吡格雷家兔血小板聚集率与创伤性出血的影响。方法选取21只健康家兔,随机分为3组,A组为对照组,给予生理盐水5 ml·kg-1·d-1灌胃,B、C组给予浓度为0.575 mg/ml的氯吡格雷药液5 ml·kg-1·d-1灌胃,B组连续灌胃7 d,C组连续灌胃14 d。检测3组家兔服药前、服药7、14 d的血小板聚集率、血小板计数,并检测各组家兔服药14 d的出血时间、凝血时间,记录创伤的出血量。结果 3组家兔服药前血小板聚集率及血小板计数无明显差异(P>0.05)。服药后第7天,B、C组家兔血小板聚集率较A组明显降低(P<0.001);第14天,B组家兔血小板聚集率与A组比较无显著差异(P>0.05),出血时间无明显延长,创伤性出血量无明显增加(P>0.05)。第14天C组血小板聚集率与A、B组相比显著降低(P<0.001),C组的出血时间较A、B组显著延长(P<0.01),创伤性出血量较A、B组有所增加,但无统计学差异(P>0.05)。B、C组家兔凝血时间及血小板计数与A组比较无显著差异(P>0.05)。创伤性出血量与血小板聚集率无显著相关性。结论不停用常规剂量的氯吡格雷未明显增加创伤性出血量;血小板聚集率暂不能作为术前停药的参考指标。     

不同维持剂量氯吡格雷对择期经皮冠脉介入治疗患者术后血小板聚集率的影响

目的 探讨不同维持剂量氯吡格雷对择期经皮冠脉介入治疗(PCI)患者血小板聚集率的影响及其临床意义.方法 随机双盲将118例择期PCI患者分为A、B两组,术前600 mg负荷剂量相同,术后第1天开始分别给予不同剂量氯吡格雷(波立维、法国赛诺菲-安万特公司生产)75 mg/d或150 mg/d,于术前及术后1天、7天、14天和30天评估血小板聚集率.结果 A、B两组患者术前和术后1天ADP诱导的血小板聚集率和最大聚集时间比较无显著性差异,而术后7天、14天、30天比较差异有显著性.结论 较高剂量的氯吡格雷可以降低择期PCI患者的血小板聚集功能.     

氯吡格雷和阿司匹林合用与单用阿司匹林治疗心力衰竭引起血小板聚集的结果

充血性心力衰竭 (CHF)是西方国家最常见死因之一 ,血栓是CHF常见并发症 ,严重CHF病人每年中风危险率以 4%的速度增长 ,氯吡格雷 (clopidogrel)是一种新的血小板二磷酸腺苷(ADP)受体拮抗剂 ,能减少中风、心肌缺血、心血管死亡发病率 ,对CHF病人 ,ADP受体拮抗剂是否抑制血小板功能不很清楚 ,本文对CHF伴血小板活性增强病人合用氯吡格雷和阿司匹林与单用阿司匹林的抗血小板特性进行了评估。研究对象为美国Baltimore城 88名心血管门诊CHF病人 ,所有病人左室射血分数 <40 %或收缩性CHF ,纽约心脏功能分级Ⅱ Ⅳ级 ,病人血小板活性增…     

氯吡格雷抵抗研究进展

氯吡格雷的抗血小板聚集作用在急性冠脉综合征和经皮冠状动脉介入术患者中得到广泛应用,但氯吡格雷抵抗的出现影响了其临床疗效。现就氯吡格雷抵抗的定义、临床意义、血小板聚集检测方法、发生机制及防治策略分别加以阐述。     

氯吡格雷抵抗相关因素的研究进展

临床上部分冠状动脉性心脏病患者未从氯吡格雷抗血小板治疗中获益,这就是氯吡格雷抵抗现象。氯吡格雷抵抗反映氯吡格雷抗血小板治疗失败。研究表明,氯吡格雷抵抗可能与血栓事件复发密切相关。它可能受多个因素影响,主要分为内源性和外源性两方面。现就氯吡格雷抵抗的检测方法、影响因素及临床对策进行了详细综述。     

氯吡格雷抵抗

氯吡格雷作为一种新型的二磷酸腺苷(ADP)受体拮抗剂,随着氯吡格雷阿司匹林在有缺血事件危险病人的对比试验(CAPRIE)、氯吡格雷协同阿司匹林在无ST抬高急性冠脉综合征(ACS)病人的效果研究(CURE)、经皮冠脉介入 (PCI)治疗病人CURE(PCI-CURE)等大规模临床试验结     

VerifyNow对比血小板聚集仪分析氯吡格雷药效

目的比较检测氯吡格雷抗血小板功能的2种实验方法的异同。方法随机收集207例门诊和住院急性冠状动脉综合征患者,其服用氯吡格雷后,抽取静脉血,同时进行光比浊法二磷酸腺苷诱导的血小板聚集实验与Ver-ifyNow抗血小板治疗监测系统实验,并进行分析。结果血小板聚集仪测得的血小板聚集率(PAgP)156例在40%～80%,占75.4%,25例<40%,占12.1%,26例>80%,占12.6%。VerifyNow分析P2Y_(12)受体的化学反应数值(PRU)126例在240～350,占60.9%,50例PRU<240,占24.2%,31例PRU>350,占15.0%。PAgP与PRU呈正相关,PAgP与抑制血小板聚集率(INHI)呈负相关,PAgP+INHI趋近于一个定值。结论 VerifyNow抗血小板治疗监测系统可作为氯吡格雷药效监测的良好实验方法 。     

国产和进口氯吡格雷对不稳定性心绞痛患者血小板功能的影响

目的　观察国产氯吡格雷和进口氯吡格雷对不稳定性心绞痛 (UAP)患者血小板功能的影响 ,比较两药抗血小板作用的优劣及其安全性。方法　 4 0例UAP患者随机分为 2组 ,其中国产氯吡格雷组 2 0例 ,进口氯吡格雷组 2 0例。另选健康对照组 10例。两治疗组分别于服用氯吡格雷前、服用氯吡格雷 30 0mg 2h后及服用氯吡格雷 75mg1次 d 1周后抽血查血小板聚集率及血小板活化指标。结果　UAP患者血小板聚集率及血小板活化状态较健康对照组明显增高。治疗前国产和进口氯吡格雷组的血小板聚集率及血小板活化指标无显著差异。治疗后两治疗组之间无显著差异。结论　血小板的活化在UAP的发生、发展过程中起着重要的作用。国产和进口氯吡格雷均有良好的抗血小板作用 ,两者抗血小板聚集和活化的作用相似 ,且无明显的不良反应。     

Pharmacodynamic effects of clopidogrel in pediatric cardiac patients: A comparative study of platelet aggregation response

Little data on pediatric percent platelet aggregation (%PA) exist in the literature, particularly in cardiac patients and in response to clopidogrel. The objectives were to estimate the %PA range expected in pediatric patients and to measure the clopidogrel effect on %PA in the PICOLO (Platelet Inhibition in Children on Clopidogrel) trial. To estimate a neonatal/infant %PA response range, %PA induced by 5?µM adenosine diphosphate (ADP) was assessed using light transmission aggregometry in 16?cord and 11 normal adult blood samples and prior to clopidogrel therapy in 49 neonatal and 49 infant/toddler cardiac patients enrolled in PICOLO. The %PA induced by 5?µM thrombin receptor-activating peptide (TRAP) was also assessed for 10 neonates and 21 infants/toddlers enrolled in PICOLO and compared with 11 adult samples. Percent inhibition of platelet aggregation (%IPA) induced by 5?µM ADP at steady-state clopidogrel levels was assessed in 33 neonates and 39 infants/toddlers. ADP-induced %PA was lowest in cord blood samples, intermediate in study neonates and infants/toddlers, and highest in adults. Similarly, TRAP-induced platelet aggregation was lower in neonates and infants/toddlers than adults. For all groups, %PA and %IPA were highly variable, with 11% of neonates and 13% of infants/toddlers showing <10% IPA. In conclusion, ADP- and TRAP-induced %PA is lower in pediatric cardiac patients than normal adults, but highly variable in both. The lower baseline %PA may explain why the pediatric clopidogrel dose providing 30–50% IPA (0.20?mg/kg/day) is lower than a simple weight-based extrapolation of the adult dose (75?mg/day) providing similar inhibition.     

血小板膜糖蛋白和血小板聚集率变化与冠心病的临床意义

目的观测冠心病(CHD)患者血小板膜糖蛋白(GP)、血小板最大聚集率(PAgT)、血脂水平的变化及相关性。方法选择CHD患者122例,其中稳定性心绞痛(SAP)患者54例(SAP组),不稳定性心绞痛(UAP)患者68例(UAP组),另选健康体检者48例(对照组)。又根据有无冠状动脉事件分为心血管事件组(57例)和无心血管事件组(65例)。测定各组血GP、PAgT及血脂水平。结果 UAP组患者GP、PAgT水平明显高于对照组及SAP组患者。心血管事件组GP、PAgT也明显高于无心血管事件组;SAP组患者血小板表面α颗粒GP-140、PAgT水平明显高于对照者;回归分析发现,CHD患者PAgT水平与GP、LDL-C、脂蛋白(a)呈正相关。结论 PAgT水平升高是CHD患者冠状动脉事件发生的重要因素,高脂血症可以促进血小板在冠状动脉硬化过程中的活化。     

Absence of platelet activating factor (PAF) mediated platelet aggregation: A new platelet defect

The failure of normal human platelets to aggregate in response to platelet activating factor (PAF) has not been previously observed. We report here the first case of a patient whose platelets did not aggregate to PAF on multiple occasions.     

Inhibition of platelet aggregation with prasugrel and clopidogrel: An integrated analysis in 846 subjects

This integrated analysis compared speed of onset, level of platelet inhibition, and response variability to prasugrel and clopidogrel in healthy subjects and in patients with stable coronary artery disease with data pooled from 24 clinical pharmacology studies. Data from subjects (N = 846) were categorized into the following treatment groups: prasugrel 60 mg loading dose (LD)/10 mg maintenance dose (MD), clopidogrel 300 mg LD/75 mg MD, or clopidogrel 600 mg LD/75 mg MDs. Maximum platelet aggregation (MPA) and inhibition of platelet aggregation (IPA) to 5 and 20 μM ADP were assessed by turbidimetric aggregometry. A linear mixed-effect model compared the MPA and IPA between treatments over time points evaluated in the integrated database, and covariates affecting platelet inhibition were identified. Prasugrel 60 mg LD resulted in faster onset, greater magnitude, and more consistent levels of inhibition of platelet function compared to either clopidogrel 300 mg or 600 mg LDs. Greater and more consistent levels of platelet inhibition were observed with the prasugrel 10 mg MD compared to the clopidogrel 75 mg MD. This integrated analysis confirms the findings of earlier individual studies, that prasugrel achieves faster onset of greater extent and more consistent platelet inhibition compared to the approved and higher loading doses of clopidogrel. Gender, race, body weight, and age were identified as statistically significant covariates impacting platelet inhibition.     

Effect of combined administration of clopidogrel and lysine acetylsalicylate versus clopidogrel and aspirin on platelet aggregation and activated GPIIb/IIIa expression in healthy volunteers

Platelet activation contributes to thrombotic events in cardiovascular disease. Acetylsalicylic acid (ASA) is used in combination with clopidogrel to reduce cardiovascular events. Lysine acetylsalicylate (L-ASA), also inhibits platelet activation with fewer gastrointestinal side effects than ASA. Dual therapy with L-ASA and clopidogrel may result in an antiplatelet effect with fewer side effects. We compared the antiplatelet effect of combined ASA/clopidogrel versus L-ASA/clopidogrel in healthy subjects. Fourteen volunteers (seven men and seven women, aged 25–45 years) received antiplatelet therapy during 14-day periods in the following sequence: 75?mg ASA; 160?mg L-ASA; 75?mg clopidogrel; 160?mg L-ASA plus 75?mg clopidogrel, and 75?mg ASA plus 75?mg clopidogrel. We evaluated platelet aggregation and glycoprotein IIb/IIIa activation. Our results show that administration of L-ASA/clopidogrel is as effective as ASA/clopidogrel combination.     

Platelet aggregability and platelet volume in the postoperative course: problems in the platelet aggregation test derived from the measurement of platelet volume

Platelet count, aggregability and volume in the postoperative course of 20 patients were examined. Platelet count was decreased on the 1st postoperative d, and increased on the 7th and 14th d compared with the preoperative value. The maximal aggregation rate of platelets induced by ADP was decreased on the 3rd postoperative d, and then recovered to the preoperative level. In contrast, platelet volume was only slightly increased on the 3rd postoperative d. In this study, there was no correlation between platelet aggregability and platelet volume in PRP. We have proposed one parameter, 'platelet concentration ratio' (platelet concentration in PRP/platelet concentration in whole blood). In the postoperative course, this concentration ratio changed depending on platelet volume, and possibly on other conditions of blood such as hematocrit, viscosity and specific gravity. The concentration ratio influenced the subpopulations of platelets in PRP. Platelet aggregation tests may be performed using PRP in which platelet subpopulations differ from those in whole blood, especially in the postoperative state.     

国产与进口硫酸氢氯吡格雷在经皮冠状动脉介入治疗中应用的有效性和安全性对照研究

目的比较冠状动脉支架术后国产硫酸氢氯吡格雷（泰嘉）与进口硫酸氢氯吡格雷（波立维）临床应用的疗效和安全性。方法人选冠心病接受冠状动脉药物洗脱支架置人术的患者共210例,随机分为泰嘉组103例,波立维组107例。所有入选患者术前1天均应用阿司匹林300mg,1次／d,硫酸氢氯吡格雷首次300mg,以后75mg,1次／d,1年,术后如为三支血管病变,硫酸氢氯吡格雷服用150mg,1次／d,2周后改为75mg,1次,d,至少服用1年。研究主要终点为随访6个月的主要心血管事件（包括死亡、支架内血栓形成、支架内再狭窄、非致死性心肌梗死、靶血管血运重建）、脑卒中的发生率;次要终点为血小板聚集率的变化以及一般出血事件的发生率。结果两组患者主要心血管事件差异无统计学意义（P〉0．05）;随访6个月两组患者的血小板聚集率及一般出血事件的发生率均无统计学差异（P〉0．05）。结论国产硫酸氢氯吡格雷（泰嘉）作为冠状动脉药物洗脱支架术后6个月联合阿司匹林强化抗血小板的药物安全有效。