不同抗血小板药物联合治疗进展性脑梗死的比较

目的比较不同抗血小板药物(阿司匹林、氯吡格雷和奥扎格雷)联合治疗对进展性脑梗死患者的血小板活化水平和神经功能的影响。方法将97例急性进展性脑梗死患者随机分为A组(阿司匹林+氯吡格雷)、B组(阿司匹林+奥扎格雷)、C组(氯吡格雷+奥扎格雷),分别比较各组患者在治疗前、治疗3天后和治疗14天后血小板CD62P表达水平和临床神经功能缺损程度评分。结果三组患者联合抗血小板治疗14天后,与同组治疗前相比,血小板CD62P的表达水平和神经功能缺损程度评分均有明显下降(P<0.05),其中A组(阿司匹林+氯吡格雷)和C组(氯吡格雷+奥扎格雷)较B组(阿司匹林+奥扎格雷)下降更明显,差异有统计学意义(P<0.05)。结论对于进展性脑梗死患者尽早联合使用两种抗血小板药物治疗,可以取得较好的疗效,其中阿司匹林联合氯吡格雷和氯吡格雷联合奥扎格雷方案治疗效果更好。     

氯吡格雷联合阿司匹林对老年不稳定型心绞痛患者血小板活化的临床干预研究

目的通过观察氯吡格雷联合阿司匹林对老年不稳定型心绞痛(UAP)患者血小板活化的影响,探讨其临床意义。方法应用流式细胞仪,分别对老年UAP患者与健康老年人血小板活化标记物CD62p、CD63进行检测,同时动态观察UAP患者应用氯吡格雷联合阿司匹林治疗前后CD62p、CD63水平的变化。结果UAP患者CD62p、CD63水平高于正常对照组;氯吡格雷联合阿司匹林治疗后,UAP患者CD62p、CD63水平较单用阿司匹林明显降低,而不影响血小板体积(MPV)和血小板计数(PLT)。结论老年UAP患者血小板活化水平升高,氯吡格雷联合阿司匹林可使血小板活化受到更为明显的抑制。     

血栓弹力图对大面积脑梗死不同剂量抗血小板聚集药物疗效的评估价值

目的应用血栓弹力图(TEG)评估大面积脑梗死急性期患者高、低剂量阿司匹林联用氯吡格雷对血小板抑制率的影响。方法回顾性纳入北华大学附属医院接诊的急性大面积脑梗死患者,并按阿司匹林口服剂量的不同分为低剂量组(阿司匹林100 mg+氯吡格雷75 mg)52例和高剂量组(阿司匹林300 mg+氯吡格雷75 mg)62例。两组患者均于入院后开始服用阿司匹林及氯吡格雷,于服药第4天,采用TEG检测患者花生四烯酸(AA)途径血小板抑制率和二磷酸腺苷(ADP)途径血小板抑制率。比较两组患者血小板抑制情况及药物抵抗的发生情况。结果低剂量组AA抑制率及ADP抑制率与高剂量组均无统计学差异(均P>0.05)。低剂量组发生阿司匹林抵抗及氯吡格雷抵抗与高剂量组无统计学差异(均P>0.05)。低剂量组脑梗死出血转化发生率与高剂量组无统计学差异(P>0.05)。结论对大面积脑梗死患者,TEG评价的低剂量与高剂量抗血小板聚集治疗对血小板抑制效果无明显差异。     

西洛他唑与氯吡格雷用于急性期脑梗死的抗血小板作用比较

目的比较西洛他唑与氯吡格雷用于急性期脑梗死的抗血小板作用。方法选择2013年12月—2015年1月广东省普宁市人民医院神经内科住院治疗的急性期脑梗死患者72例,随机分为西洛他唑组和氯吡格雷组,每组36例。在常规治疗基础上西洛他唑组加用西洛他唑治疗,氯吡格雷组加用氯吡格雷治疗。比较两组患者用药前及用药第8天神经功能缺损评分,用药前、用药第3天及用药第8天血小板P-选择素(CD62P)、血小板纤维蛋白原受体(PAC-1)水平,同时观察治疗期间不良反应发生情况。结果两组患者用药前后神经功能缺损评分比较,差异无统计学意义(P0.05)。用药第3天,氯吡格雷组血小板CD62P、PAC-1水平低于西洛他唑组(P0.05);用药前及用药第8天两组患者血小板CD62P、PAC-1水平比较,差异无统计学意义(P0.05)。两组患者治疗期间均未出现明显不良反应。结论西洛他唑与氯吡格雷治疗急性期脑梗死均具有较好的抗血小板作用,能有效抑制血小板聚集,但氯吡格雷较西洛他唑起效快。     

血栓弹力图在急性脑梗死患者抗血小板治疗效果评价中的应用

目的探讨采用血栓弹力图(TEG)评价阿司匹林和氯吡格雷治疗急性脑梗死患者的抗血小板效果,以指导对急性脑梗死患者抗血小板聚集药物治疗的个体化调整。方法选择急性脑梗死患者82例,予阿司匹林100 mg和氯吡格雷75 mg联合治疗7 d后,采用TEG仪检测花生四烯酸(AA)途径诱导的血小板抑制率和腺苷二酸(ADP)受体途径诱导的血小板抑制率,比较患者经两种途径诱导的血小板抑制率以及患者对阿司匹林和氯吡格雷治疗反应的差异。同时选择急性脑梗死患者40例作为对照组,单用阿司匹林100 mg抗血小板治疗7d,对比两组TEG参数(R值、K值、angle角、MA值)。结果急性脑梗死予阿司匹林、氯吡格雷双抗血小板,阿司匹林对AA途径的抑制率明显高于氯吡格雷对ADP受体途径的抑制率,差异有统计学意义(P0.01);对阿司匹林反应良好的患者,4例对氯吡格雷无反应,15例反应低下;对氯吡格雷反应良好的患者,仅1例对阿司匹林反应低下。对氯吡格雷反应低下者,3例对阿司匹林无反应,5例低下,6例对阿司匹林有效,15例良好。两种疗效有一定关联性(P0.01)。对阿司匹林反应良好+有效为62例,反应低下+无效者20例;氯吡格雷反应良好+有效者42例;反应低下+无效者38例,两种药物疗效差异有统计学意义(P0.01)。单用阿司匹林组与双联抗血小板组比较两组患者R值、K值、α角、MA值均无明显差别(P0.05)。结论采用TEG仪检测对急性脑梗死患者抗血小板治疗的疗效评价有较高的临床价值。双联抗血小板中阿司匹林对急性脑梗死患者血小板聚集的抑制作用强于氯吡格雷。患者对阿司匹林和氯吡格雷治疗的反应有差异性,部分对氯吡格雷反应低下者,可能对阿司匹林反应良好或有效。双联抗血小板治疗对血凝的影响较单用阿司匹林无明显差别。     

阿司匹林或氯吡格雷作用下血小板不同活化途径的反应特点

目的探讨阿司匹林和氯吡格雷抑制血小板环氧酶(COX)-1途径和P2Y12受体活化的特点及两途径之间的交互关系。方法 20例健康男性志愿者按随机数余数分组法平均分为两组,分别服用阿司匹林(100 mg/d)和氯吡格雷(75 mg/d)连续7 d。并在服药和停药后第1、3、5、7天分别应用血栓弹力图、血小板功能分析仪和流式细胞仪观察血小板的抑制情况。结果服药后,氯吡格雷组的胶原-肾上腺素激活的闭孔时间(CEPI-CT)和胶原-腺苷二磷酸闭孔时间(CADP-CT)的变化差异均有统计学意义(F=27.2,P<0.01,F=25.3,P<0.05),阿司匹林组CEPI-CT迅速增至检测上限300 s,差异有统计学意义(F=36.7,P<0.01),而CADP-CT变化差异无统计学意义(F=2.12,P=0.13)。服药后阿司匹林组血小板COX-1途径抑制率增高至91.7%±0.9%(F=35.1,P<0.01),氯吡格雷组P2Y12受体抑制率由47.8%±3.1%增高至81.3%±3.8%(F=24.8,P<0.01),COX-1未受到有效抑制(F=1.85,P=0.11)。服药后两组CD62p表达降低50%(氯吡格雷组:F=28.7,P<0.01;阿司匹林组:F=20.7,P=0.02)。结论花生四烯酸诱导的COX-1途径活化与P2Y12受体活化可能存在交互作用,床旁即时检验有助于快速了解血小板功能状态,为监测有效的联合用药提供依据。     

高龄老年应用氯吡格雷与阿司匹林抗血小板治疗的临床研究

目的对比研究高龄老年应用氯吡格雷与阿司匹林抗血小板治疗的效果及安全性。方法91例高龄老年冠心病患者随机分为氯吡格雷组(50 mg/d)、阿司匹林组(100 mg/d)及对照组(复方丹参滴丸10粒3次/d),药物治疗8周后,观察实验前后血小板聚集率改变、胃黏膜出血、对中性粒细胞及血小板的影响以及凝血三项的改变。结果与对照组比较,氯吡格雷组与阿司匹林组对血小板聚集率均有确切的抑制作用;在血小板聚集率抑制方面,氯吡格雷组优于阿司匹林组;各组实验前后均未出现中性粒细胞及血小板的显著变化;在胃黏膜损伤方面,虽然阿司匹林组发生例数较多,但各组均无显著差异;阿司匹林组及对照组实验前后凝血指标未发生变化,氯吡格雷组用药后活化部分凝血酶时间延长,与对照组比较有显著差异,而用药前两组无显著差异。结论高龄老年应用氯吡格雷与阿司匹林均能获得确切的抗血小板聚集效果,且较安全,其中氯吡格雷效果优于阿司匹林。     

大鼠模型中糖尿病导致氯吡格雷治疗后血小板高反应性的机制研究

目的在大鼠模型中探讨糖尿病对氯吡格雷治疗后血小板高反应性(HTPR)的影响及其可能的影响机制。方法造模成功的雄性SD大鼠45只,随机分为空白组11只、氯吡格雷组11只、糖尿病组11只和糖尿病+氯吡格雷组(实验组)12只,普通饲料饲养8周,采用灌胃法给予氯吡格雷,糖尿病模型采用链脲佐菌素(STZ)一次性注射法建立。流式细胞术检测CD62P水平和细胞质内Ca2+水平,ELISA法检测同型半胱氨酸(Hcy)、高敏C反应蛋白(hs-CRP)、超氧化物歧化酶(SOD)、丙二醛(MDA)、血栓素A2(TXA2)、前列环素(PGI2)及NO等水平,RT-PCR和Westernblot检测细胞色素450(CYP450)、蛋白激酶C(PKC)及P2Y12受体基因和蛋白表达。结果糖尿病组和实验组血糖、Hcy、MDA、TXA2、hs-CRP水平、P2Y12基因和蛋白及PKC蛋白表达显著高于空白组和氯吡格雷组(P<0.01);PGI2、SOD及NO、ADP诱导的血小板聚集抑制率(ADP-IR)、CYP450蛋白表达显著低于空白组和氯吡格雷组(P<0.01)。实验组ADP-IR显著低于糖尿病组[(45.64±13.31)%vs(80.14±4.30)%,P<0.01]。糖尿病组CD62P、细胞质内Ca2+水平明显高于其他组(P<0.01);且实验组明显高于空白组和氯吡格雷组(P<0.05,P<0.01);氯吡格雷组细胞质内Ca2+水平显著低于空白组(P<0.05)。各组PKC和CYP450基因表达比较,差异无统计学意义(P>0.05)。ADP-IR与SOD和TXA2水平呈负相关(P<0.05,P<0.01);CD62P水平与细胞质内Ca2+水平呈正相关(P<0.01)。ADP-IR与CD62P水平呈负相关(r=-0.3567,P=0.015)。结论糖尿病导致氯吡格雷HTPR的机制为血小板功能异常、血小板表面受体表达上调及氯吡格雷活化相关酶系表达减少。     

不同抗血小板治疗对经皮冠状动脉介入术后氯吡格雷抵抗患者血小板miR-223、血小板抑制率及血小板活化指标的影响

目的:探讨不同抗血小板治疗方案对经皮冠状动脉介入术(PCI)后氯吡格雷抵抗患者血小板微小RNA-223(miR-223)、血小板抑制率及血小板活化指标的影响。方法:将160例PCI后氯吡格雷抵抗患者随机分为氯吡格雷双倍组(n=80,氯吡格雷150 mg,每日1次)和替格瑞洛组(n=80,替格瑞洛90 mg/次,每日2次)。比较两组治疗前后血小板抑制率、血小板miR-223、血小板α颗粒表面膜糖蛋白(CD62P)、活化血小板糖基化复合物(PAC-1)的变化。随访6个月,记录两组主要不良心血管事件(MACE)、出血事件及呼吸困难的发生情况。结果:治疗7 d、30 d后,替格瑞洛组血小板抑制率均明显高于氯吡格雷双倍组(P均0.05)。治疗30 d后,替格瑞洛组血小板miR-223、CD62P、PAC-1表达水平均明显低于氯吡格雷双倍组(P均0.05)。随访6个月,替格瑞洛组MACE发生率明显低于氯吡格雷双倍组(3.75%对13.75%,P0.05);两组出血事件发生率的差异无统计学意义,但替格瑞洛组呼吸困难发生率明显高于氯吡格雷双倍组(11.25%对16.25%,P0.05)。结论:对于PCI后氯吡格雷抵抗的冠状动脉粥样硬化性心脏病患者,替格瑞洛较双倍剂量氯吡格雷能够更好地抑制血小板聚集,减少MACE,且不增加出血风险。但替格瑞洛易引起呼吸困难,临床应予以足够重视。     

达肝素钠对兔血小板功能的影响及阿司匹林和氯吡格雷的干预作用

目的 研究达肝素钠对兔血小板活化的影响以及阿司匹林和氯吡格雷的干预.方法　纯种新西兰家兔12只,给予阿司匹林或氯吡格雷或二者合用喂饲,静脉注射达肝素钠前及注射后20、30 min检测ADP、AA诱导的血小板聚集、血浆CD62P和vWF的水平.结果 应用达肝素钠后血小板聚集、CD62及vWF无明显增加;与基线水平比较,阿司匹林组加用氯吡格雷两药合用,静脉注射达肝素钠前(9.50±4.18 vs 2.67±1.63)及注射后20 min(10.50±3.21 vs 2.83±1.66)ADP 诱导的血小板聚集均明显降低.单用阿司匹林喂饲7 d,应用达肝素钠后血小板聚集增加(7.00±4.10 vs 12.50±4.04).结论 达肝素钠不会引起血小板激活;阿司匹林与达肝素钠合用增加血小板聚集;氯吡格雷与阿司匹林两药合用明显降低血小板聚集.     

Serial changes in platelet activation in patients with unstable angina following coronary stenting: evaluation of the effects of clopidogrel loading dose in inhibiting platelet activation.

BACKGROUND: Platelet activation is crucial in the development of acute or subacute stent thrombosis following implantation. This study investigated whether a conventional regimen comprising a loading dose of 300 mg of clopidogrel, followed by daily doses of 75 mg, could significantly suppress platelet activation in patients with unstable angina (UA) undergoing coronary stenting. METHODS AND RESULTS: Platelet activation (expressed by CD62p) was serially examined using flow cytometry in 42 consecutive patients with UA who underwent coronary stenting. CD62p expression was also evaluated in 30 normal control subjects. CD62p expression was markedly higher pre-procedure in the study patients than in the normal control subjects (5.2+/-4.0% vs 1.4+/-0.6%, p<0.0001). CD62p expression in the study patients remained significantly higher at 24 h after the procedure than in the control subjects (3.8+/-2.1% vs 1.4+/-0.6%, p<0.001). Additionally, only 26% of CD62p expression (5.2% vs 3.8%, p=0.026) in the study patients was suppressed at 24 h after the procedure. However, more than 60% of CD62p expression (5.2% vs 2.0%, p<0.0001) was suppressed on day 7 after the procedure. CONCLUSION: Less than one-third of CD62p expression was suppressed at 24 h by the conventional loading dose (300 mg) of clopidogrel in patients with UA following coronary stenting. This finding indicates the need to evaluate whether an increased loading dose of clopidogrel would be a more efficacious and safe regimen for patients in this clinical setting.     

阿司匹林与氯吡格雷对急性脑梗死患者血小板CD62P和CD63表达的影响

<正>急性脑梗死(ACI)是中老年人群中的常见病,具有高发病率、高致残率和高死亡率的特点,是危害我国人民群众生命健康的主要原因之一,其发病机制十分复杂。近年来对于血小板活化功能亢进与缺血性脑血管病的关系日益受到重视。血小板α-颗粒膜蛋     

Antiplatelet effects of clopidogrel compared with aspirin after myocardial infarction: enhanced inhibitory effects of combination therapy

OBJECTIVES: We sought to compare the inhibitory effects of the combination of two doses of aspirin plus clopidogrel with either drug alone on platelet aggregation and activation. BACKGROUND: Enhanced platelet inhibitory effects of clopidogrel by aspirin on platelet aggregation and activation are suggested by experimental studies but have not been shown in humans. METHODS: The effects of clopidogrel 75 mg or aspirin 100 (300) mg on platelet aggregation and activation by flow cytometry after stimulation with various agonists were determined in 30 patients with a past history of myocardial infarction. RESULTS: Clopidogrel alone or in combination with aspirin markedly inhibited adenosine diphosphate (ADP)-mediated platelet aggregation compared with monotherapy with aspirin (24.6 +/- 3.3% or 26.6 +/- 2.7% vs. 44.7 +/- 2.9%; p < 0.001). Combined treatment significantly inhibited collagen-induced aggregation compared with aspirin and clopidogrel (16.4 +/- 2.4%, 36.5 +/- 4.2% and 59.3 +/- 5.1%, respectively;, p < 0.001) and resulted in considerable inhibition of aggregation induced by thrombin receptor agonist peptide (TRAP, p < 0.03). Clopidogrel with or without aspirin significantly suppressed expression of platelet activation markers CD 62p, CD 63 and PAC-1 after stimulation with ADP or thrombin (p < 0.001). In addition, the combined treatment was more effective than either agent alone after activation with low dose thrombin (p < 0.05). Both doses of aspirin equally potentiated the platelet inhibitory effects of clopidogrel. CONCLUSIONS In this prospective clinical ex vivo platelet study, clopidogrel was more effective than aspirin in inhibiting ADP-mediated platelet aggregation and activation. Clopidogrel in combination with aspirin showed synergistic inhibitory effects after stimulation with collagen and thrombin compared with monotherapies. Thus, this dual antiplatelet treatment strategy deserves further evaluation in clinical trials for secondary prevention of acute myocardial infarction or unstable angina.     

Time course of platelet activation and von Willebrand factor in patients with non-valvular atrial fibrillation after ischemic stroke.

BACKGROUND: The present study investigated serial changes in platelet activation (expressed by CD62p) and von Willebrand factor (VWF), and the correlation between increased CD62p expression, VWF and brain infarct volume (BIV: measured by magnetic resonance imaging), and prognostic determinants in non-valvular atrial fibrillation (NVAF) patients after acute ischemic stroke (IS). METHODS AND RESULTS: CD62p expression and plasma VWF concentrations were serially measured (<48 h, on days 7, 21 and 90) using flow cytometry and enzyme-linked immunosorbent assay, respectively after acute IS in 61 NVAF patients. CD62p expression and VWF concentrations were also examined in 50 NVAF-risk control and 30 healthy individuals. The VWF concentration had no significant changes at 4 intervals among the patients and did not differ among 3 groups at acute stroke phase. CD62p expression was significantly higher in the acute phase after IS than in both control groups (both p<0.0001). However, CD62p expression declined to a significantly lower level on day 7 and to a substantially lower level thereafter (p<0.0001). CD62p expression did not differ on day 90 in the 3 groups (both p>0.5). Linear regression analysis showed that BIV and modified Rankin scale score (>3) were independently associated with increased CD62p expression (<48 h) (both p<0.01). Furthermore, the Cox proportional hazards model showed that BIV was the only independent predictor of intermediate-term (8.8+/-4.4 months) combined recurrent stroke and death. CONCLUSIONS: The CD62p expression, which reflected increased BIV, was significantly increased in NVAF patients in acute-phase IS and substantially declined thereafter. The BIV was predictive of unfavorable intermediate-term clinical outcomes.     

The effects of aspirin and ticagrelor on Toll-like receptor (TLR)-mediated platelet activation: results of a randomized,cross-over trial

Platelet activation underlies the pathology of an acute myocardial infarction (AMI), and dual antiplatelet therapy (DAPT) is administered post-AMI to limit this activation. Platelets express Toll-like receptors (TLRs) 1, 2, and 4 and become potently activated in response to TLR2/1 and TLR4 stimulation. However, it is unknown whether antiplatelet agents can protect against platelet activation via these TLR pathways. This study aimed to determine the extent to which TLR-mediated platelet activation can be inhibited by currently used antiplatelet agents. Ten healthy subjects were enrolled into a single-blinded randomized cross-over trial. Subjects received either aspirin monotherapy or DAPT (aspirin in combination with ticagrelor) for 1 week, were washed out, and crossed over to the other drug regimen. Platelet activation was assessed in response to Pam3CSK4 (a TLR2/1 agonist) and lipopolysaccharide (LPS; a TLR4 agonist) at baseline and after each antiplatelet drug regimen. Platelet-surface expression of CD62p and PAC1 by flow cytometry was measured as markers of platelet activation. At baseline, expression of CD62p and PAC1 increased significantly in response to high-dose LPS and in a dose-dependent manner in response to Pam3CSK4. Aspirin monotherapy did not inhibit platelet activation in response to any TLR agonist tested. DAPT with aspirin and ticagrelor only modestly inhibited expression of both activation markers in response to high doses of Pam3CSK4 and LPS. However, incubation with these TLR agonists led to substantial platelet activation despite treatment with these anti-platelet agents. Platelet-TLR2/1 and platelet-TLR4 represent intact on-treatment platelet activation pathways, which may contribute to on-going platelet activation post-AMI.     

三联抗血小板药物对缺血性脑血管病患者冠状动脉介入治疗术后的近期疗效

目的探讨既往有缺血性脑血管事件发作史的冠心病患者行经皮冠状动脉介入治疗(PCI)后应用西洛他唑联合阿司匹林和氯吡格雷三联抗血小板治疗方案的近期疗效和安全性。方法回顾性分析有缺血性脑血管病史且接受PCI治疗的冠心病患者共216例,其中80例PCI后应用三联抗血小扳治疗(三联组),136例PCI后应用阿司匹林联合氯吡格雷两联抗血小板治疗(两联组)。观察两组PCI后30天主要不良心脑血管事件(MACCE)、亚急性血栓和出血发生率结果两组临床基线特征及PCI即刻结果无差异,术中均无死亡;三联组患者30天病死率、脑卒中发生率、MACCE发生率均显著低于两联组(P值分别<0．05,<0．05,<0．01)。两组亚急性血栓、30天主要出血事件、脑出血发生率差异均无显著性意义。结论有缺血性脑血管病史患者PCI后应用氯吡格雷、阿司匹林和西洛他唑三联抗血小板治疗后,可显著降低近期死亡、脑卒中及MACCE发生率,且不增加脑出血等副作用。     

Platelet activity is a biomarker of cardiac necrosis and predictive of untoward clinical outcomes in patients with acute myocardial infarction undergoing primary coronary stenting.

BACKGROUND: The relationship between platelet activity and myocardial injury in patients with ST-segment elevated (ST-se) acute myocardial infarction (AMI) remains unclear. This study tested the hypothesis that platelet activity (expressed by CD62p) is enhanced and predictive of both the extent of myocardial damage and 30-day clinical outcome in patients with ST-se AMI undergoing primary coronary stenting. METHODS AND RESULTS: Platelet CD62p expression prior to coronary angiographic was prospectively measured using flow cytometry in 45 consecutive patients with AMI undergoing primary coronary stenting. The CD62p expression was also evaluated in 20 healthy and 20 at-risk control subjects. The CD62p expression was significantly higher in AMI patients than in healthy and at-risk control subjects (all p values <0.0001). Patients with high CD62p expression (>or=8%) had significantly higher creatine kinase-MB (p<0.0001) levels, higher incidence of cardiogenic shock (p=0.009) upon presentation, significantly lower left ventricular ejection fraction (p=0.0003), and significantly higher incidence of 30-day composite major adverse clinical outcomes (MACO) (advanced congestive heart failure >or=class 3 or 30-day mortality) (p<0.0001) than those patients with low CD62p expression (<8%). Multiple stepwise logistic regression analysis demonstrated that only high CD62p expression (>or=8%) was an independent predictor of 30-day MACO (all p<0.0001). CONCLUSIONS: Platelet activation was significantly increased in patients with ST-se AMI. Initial CD62p expression was independently associated with extent of myocardial damage and 30-day MACO.     

Clinical utility of remote platelet function measurement using P-selectin: assessment of aspirin,clopidogrel, and prasugrel and bleeding disorders

Vascular diseases such as myocardial infarction and ischemic stroke are associated with increased platelet function whilst the risk of recurrence is reduced by antiplatelet agents such as aspirin, clopidogrel, and prasugrel. However, some patients exhibit high platelet reactivity, especially with clopidogrel. Existing platelet function tests may not be ideal in that they can be expensive, are often time consuming, and measurements must be made near to the patient and within a few hours of blood collection. Platelet activation leads to translocation of P-selectin from alpha-granules to the cell surface. Following activation with arachidonic acid (which is blocked by aspirin) or adenosine diphosphate (inhibited by clopidogrel) and fixation, samples may be stored or posted to a laboratory performing flow cytometric quantification of platelet P-selectin expression. Acute myocardial infarction and ischemic stroke are associated with high platelet reactivity on clopidogrel in 6–58% of patients when assessed with P-selectin expression, and high reactivity was associated with an increased risk of recurrence after myocardial infarction. Use of P-selectin expression tests may also be of relevance to surgical and veterinary practice and the diagnosis of mild bleeding disorders. The present review explores this topic in further detail.     

The effects of antiplatelet agents on platelet–leukocyte aggregations in patients with acute cerebral infarction

Background Studies have shown that platelet-leukocyte aggregates (PLA) are sensitive to platelet activation which might exist before the onset of cerebral infarction. In this study, we investigated the formation of PLA in patients with cerebral infarction and the effects of antiplatelet agents on PLA. Methods The level of soluble P-selectin, C-reaction protein, platelet aggregation rate and leukocyte-platelet aggregations were measured in 40 patients with acute cerebral infarction and 20 normal controls. The 40 patients were randomly assigned to two treatment groups: aspirin group (n = 20) and clopidogrel group (n = 20). Both groups were monitored for Scandinavian stroke scale (SNSS), soluble P-selectin, serum C-reaction protein, platelet aggregation rate and PLA before and after the treatment. Flow cytometry was used to detect the levels of PLA in the blood. Results The percentage of platelet-monocyte aggregates (PMA) in patients with cerebral infarction was significantly increased compared with the controls (P < 0.001), which was positively correlated to soluble P-selectin, C-reaction protein and platelet aggregation rate (P < 0.05). After the treatment, the levels of PMA and platelet aggregation rate were decreased in both groups (P < 0.05). The level of PMA and platelet aggregation rate in the clopidogrel group was significantly lower than that in the aspirin group (P < 0.05). Conclusions PMA are a sensitive biomarker to platelet activation in patients with cerebral infarction. In addition, although both aspirin and clopidogrel lowered the level of PMA, clopidogrel is a more effective treatment than aspirin in inhibiting platelet activation.     

不同质子泵抑制剂对冠脉支架术后氯吡格雷抗血小板功能的影响

目的:观察埃索美拉唑、雷贝拉唑、雷尼替丁或法莫替丁对急性冠脉综合症（ACS）患者冠脉支架术后应用氯吡格雷抗血小板功能的影响。方法: 150例行经皮冠状动脉介入治疗（PCI）的ACS患者,入院后给予阿司匹林300 mg/d,氯吡格雷300 mg负荷剂量继以75 mg/d维持剂量抗血小板治疗,并随机分为质子泵抑制剂（PPI）A组（A1组:埃索美拉唑40 mg/d,n=30,A2组:雷贝拉唑20 mg/d,n=30）、H2受体拮抗剂(H2RA)B组（B1组:雷尼替丁300 mg/d,n=30,B2组:法莫替丁40 mg/d,n=30）和空白对照C组（C组:n=30）。采用ELISA法检测血浆CD62P、GPⅡb/Ⅲa含量及电阻抗法检测血小板聚集功能。结果: PPI或H2RA治疗前后,A组、B组与C组相比,上述指标的差值组间比较均无明显统计学差异,A1组、A2组、B1组、B2组与C组相比,治疗前后上述指标的差值组间比较均无统计学差异。结论: 埃索美拉唑、雷贝拉唑、雷尼替丁或法莫替丁对氯吡格雷的抗血小板活性无明显的影响。