急性脑梗死患者血小板参数的临床分析

目的:研究急性脑梗死患者平均血小板体积(MPV)、血小板计数(PLT)、血小板分布宽度(PDW)的特点及临床意义.方法:将2109例急性脑梗死患者按合并症分为5组:单纯脑梗死组297例、合并高血压组635例、合并糖尿病组456例、合并房颤组209例和合并血脂异常组512例.按是否复发分为初发组1458例,复发组651例.比较2109例脑梗死患者与480例健康体检者(对照组)的MPV、PLT和PDW.结果:脑梗死组MPV高于对照组,差异有统计学意义(P＜0.05),2组间PLT、PDW比较差异无统计学意义(P＞0.05).5个脑梗死亚组间MPV、PLT水平差异有统计学意义(P＜0.05):单纯脑梗死组MPV较其他组减小,合并房颤组MPV较其他组均增大(P＜0.05或P＜0.01),合并房颤组PLT较其他组减少(P＜0.05);合并高血压组、合并糖尿病组、合并血脂异常组的MPV 、PLT、PDW差异无统计学意义(P＞0.05).复发组与初发组的MPV、PLT、PDW差异无统计学意义(P＞0.05).结论:检测MPV对急性脑梗死的预防有重要意义,尤其对有合并症的患者.     

PLATELET KINETICS AFTER TRANSFUSION

A kinetics model is proposed for platelet disposition after transfusion of platelets. In this model, transfusion of platelets and production of endogenous platelets contribute to an increase in the number of platelets in patients, and the life span and age of each platelet contribute to a decrease. The time course of the number of platelets after transfusion of platelets is theoretically described by this model to be a straight line followed by a concave curve. When the platelets have a life span without any variation, a linear pattern is observed in spite of their different ages at the transfusion. This model with a constant life span was applied to three patients receiving platelet transfusion, and the model parameters were calculated by curve fitting the observed platelet levels to the model using the nonlinear least-squares method. As a result, the life span, distribution volume per body weight, and endogenous platelet level (averages for three patients) were calculated as 6·29 d, 0·137 L kg⁻¹, and 1·40×10⁴ counts μL⁻¹, respectively. The calculated platelet levels in individual patients were compared with the observed ones during the next transfusions, and the relative and absolute differences between calculated and observed values were 2·0±15.3% and −0·075±0·443×10⁴ counts μL⁻¹ (mean±SD, 15 observed points for three patients), respectively. These case studies suggest that the model could be clinically useful for individual platelet transfusion.     

肺癌根治术患者手术前后血小板数量 、比积和分布宽度的变化及临床意义

目的 探讨肺癌根治术前、后病患血小板数量(PLT)、血小板比积(PCT)以及血小板分布宽度(PDW)水平变化,并分析其临床意义.方法 选择接受肺癌根治术患者73例,根据肺癌TMN分为ⅠA患者为IA组(n=41),ⅠB患者设为IB组(n=32);另选取同期进行健康体检的志愿者设为对照组(n=50).术后7 d后,研究者测定受试者外周血中的血小板相关指标:包括血小板数量(PLT)、血小板比积(PCT)以及血小板分布宽度(PDW).随访5年,频率为0.5年1次,统计患者的生存期限并测量其KPS评分,取其生存期限内的KPS评分的平均值.结果 肺癌患者的PLT、PCT以及PDW水平高于对照组(P<0.05).术后,ⅠA组和ⅠB组的PLT、PCT以及PDW水平均显著高于对照组(P<0.05).小细胞癌患者的PLT、PCT水平相对较高,大细胞癌患者的PDW水平相对较高(P<0.05).ⅠA组的手术时间及术后并发症例数少于ⅠB的患者,而手术中清除得到的淋巴结数目多于ⅠB病患,差异均有统计学意义(P<0.05).结论 采用常规根治术治疗肺癌能有效改变病患血小板指标,其中PLT、PCT以及PDW都有明显的降低.     

6-〔4-(取代哌嗪基)苯基5-甲基-4,5-二氢-3(2H)哒嗪酮类化合物的合成及抑制血小板聚集作用

根据哒嗪酮类化合物的构效关系和作用机制,以CCI17810 为先导化合物,设计合成了6〔4(取代哌嗪基) 苯基〕5甲基4 ,5二氢3(2 H) 哒嗪酮类化合物16 个.初步的体外药理试验表明:大部分目标化合物都有不同程度的抑制ADP诱导的新西兰大白兔血小板聚集作用,其中化合物(5)的活性最强,化合物(4) ,(6) ,(7) 也有较强的活性,并初步探讨了其构效关系     

6-{4-〔4-(取代苯乙酮基)哌嗪基〕苯基}-5-甲基-4，5-二氢-3(2H)哒嗪酮类化合物的合成及其抑制血小板聚集作用

根据哒嗪酮类化合物的构效关系和作用机制 ,以CCI 17810为先导化合物 ,设计合成了 6 〔4 (取代哌嗪基 )苯基〕 5 甲基 4,5 二氢 3(2H)哒嗪酮类化合物 12个 .初步的体外药理试验表明 :大部分目标化合物都有不同程度的抑制ADP诱导的新西兰大白兔血小板聚集的作用 ,其中化合物 (4 )的活性最强 ,比先导化合物CCI 17810大约强一倍 ,化合物 (1) ,(2 ) ,(11)也有较强的活性 .     

6-(4-取代苯基)-4,5-二氢-3(2H)-哒嗪酮类化合物的合成及血小板聚集抑制作用

为了寻找理想的血小板聚集抑制剂，设计合成了１４个６－（４－取代苯基）－４，５－二氢－３（２Ｈ）－哒嗪酮类化合物．ＡＤＰ诱导，家兔体外血小板聚集实验表明，均有不同程度的抑制作用，其中化合物（Ⅰ８）的作用最强．     

6-［4-(取代哌嗪基)苯基］-4，5-二氢-3(2H)-哒嗪酮类化合物的合成及抑制血小板聚集作用

根据哒嗪酮类化合物的构效关系和作用机制,以ＣＣＩ１７８１０ 为先导化合物,设计合成了１８ 个６［４（ 取代哌嗪基） 苯基］４,５二氢３（２ Ｈ）哒嗪酮类化合物．初步的体外药理试验表明：大部分目标化合物都有不同程度的抑制ＡＤＰ诱导的新西兰大白兔血小板聚集的作用,其中化合物（５）的活性最强,比先导化合物强５ 倍,化合物（６）,（７） ,（１２） ,（１３） ,（１６） 的活性也比ＣＣＩ１７８１０ 强,并初步探讨了它们的构效关系．     

埃索美拉唑对氯吡格雷抑制血小板作用的影响

目的观察埃索美拉唑对氯吡格雷血小板抑制作用的影响。方法 151例接受经皮冠脉介入治疗的冠状动脉疾病患者,均接受氯吡格雷负荷量600 mg治疗,在进入研究时,患者已经平均接受了3个月（至少5 d）的氯吡格雷（75 mg.d-1）和阿司匹林（100 mg.d-1）治疗。其中76例在此基础上给予埃索美拉唑（20 mg,bid）治疗,作为实验组;另外75例作为对照组。结果血小板反应指数在实验组（n=76,总体均数51%,范围48%～54%）和对照组（n=75,总体均数49%,范围43%～55%;P=0.718）的患者中几乎完全相同。埃索美拉唑（n=76;PRI=54%;聚集度42 U）和对照组（n=75;PRI=49%;聚集度=41 U;P=0.373）的患者之间,PRI或者二磷酸腺苷诱导的血小板聚集度没有差异。结论对于接受氯吡格雷治疗且同时需要抑酸干预的患者,需要质子泵抑制剂（PPI）治疗时,应尽可能的选择相互作用影响小的埃索美拉唑。     

API_（0134）对四种诱聚剂致血小板聚集的影响

采用比浊法观察到ＡＰＩ０１３４显著抑制二磷酸腺苷（ＡＤＰ）、肾上腺素（Ａｄｒ）、花生四烯酸（ＡＡ）和胶原（Ｃｏｌｌ）诱导的人和大鼠血小板聚集。ＡＰＩ０１３４体外给药（２８．８～９１０ｍｇ·Ｌ－１）呈剂量依赖性的明显抑制ＡＤＰ、Ａｄｒ和ＡＡ诱导的人血小板聚集，其中对ＡＤＰ诱导的血小板聚集抑制作用最强，１ｍｉｎ和５ｍｉｎ时的半抑制浓度（ＩＣ５０）分别为１３４ｍｇ·Ｌ－１和７６．６ｍｇ·Ｌ－１，对Ａｄｒ诱导的血小板聚集之ＩＣ５０分别为１９４和１３７．６ｍｇ·Ｌ－１，对ＡＡ诱导的血小板聚集抑制作用较弱，５ｍｉｎ时的ＩＣ５０为２０３ｍｇ·Ｌ－１，ｉｖＡＰＩ０１３４７０和１００ｍｇ·ｋｇ－１，对ＡＤＰ和Ｃｏｌｌ诱导的大鼠血小板聚集也呈显著抑制作用，抑制率分别为２７．８％～３９．５％和２４．３％～３５．０％。     

Sustained increase in platelet aggregation after the cessation of clopidogrel

This study shows that the abrupt cessation of one‐year clopidogrel treatment was not associated with thrombotic events in a prospective, multicentre study that enrolled 200 patients subjected to coronary stent implantation and treated with aspirin + clopidogrel 1 year after the stent placement. The aim of the study was to investigate the causes of a sustained increase of platelet aggregability, considering that the values of platelet aggregation stimulated with ADP + PGE₁ (ADPHS values) significantly increased 10–90 days after the cessation of clopidogrel. Values of platelet aggregation induced by thrombin receptor activating peptide (TRAP values) and arachidonic acid (ASPI values) were divided into quartiles on the basis of ADPHS values 10 days after stopping clopidogrel (ADPHS₁₀). There was a significant difference between TRAP values divided into quartiles according to ADPHS₁₀, 10, 45 and 90 days after stopping clopidogrel (P < 0.001, all), and ASPI values across the same quartiles 10 and 45 days after the cessation of clopidogrel (P = 0.028 and 0.003). The results of the study indicate that patients with early pronounced rebound phenomena to clopidogrel termination have a long‐term (at least 90 days) increased platelet aggregation to other agonists such as thrombin‐related activated protein and arachidonic acid, suggesting the complex mutual relationship of various factors/agonists influencing the function of platelets.     

PTA后肾动脉局部血小板功能变化的实验研究

为了了解肾动脉成形术前后血管局部血小板功能变化情况,在肾动脉狭窄犬模型上,对9只犬于成形术前后分别测试血管局部血小板粘附、聚集和释放功能指标,并进行比较。结果显示,9只犬在术后测得的肾动脉成形术局部血小板功能值为:血小板粘附率为(49.63±13.02)％,胶原诱导及ADP诱导的血小板聚集率为(44.66±11.70)％及(40.74±17.73)％,T/P比值为2.12±1.03,5-HT释放量为(16.81±2.33)mg/L,GMP-140释放量为(25.44±9.86)mg/L,分别高于术前相应指标数值(36.36±13.82)％,(32.07±13.91)％,(31.84±14.72)％,1.42±0.42,(11.71±4.29)mg/L及(16.49±6.83)mg/L(均P<0.05)。结果表明,伴随成形术产生的血管损伤最终导致血小板功能活化,可能是术后再狭窄形成的重要因素。     

血小板反应指数在监测阿司匹林抵抗中的临床评价

目的建立一种规范化、标准化的抗血小板药物实验监测方法。血小板反应指数（PRI）并与光学法血小板聚集试验（PAGT）进行对比，比较二者在监测抗血小板药物疗效方面的相关性，进一步证实PRI实验的可靠性和准确性。方法体检健康者350例，长期服用阿司匹林的心血管患者224例，抽取静脉血进行PAGT和PRI检测，前者血小板聚集率I〉70％为阿司匹林抵抗，后者PRI≥1．25为阿司匹林抵抗。结果健康人PRI参考范围为0．95±0．11；224例患者中，用PRI方法检测，检出阿司匹林抵抗患者30例（13．39％），用PAGT方法检出16例（7．14％）。PRI检出率明显高于血小板聚集率（P〈0．05）。结论PRI可作为监测抗血小板药物抵抗的临床常规检测技术之一，具有实用、快速、成本低、易操作、不受干扰、准确度和可靠性高的优越性。     

Svate对心肌梗塞患者血小板聚集性和形态的影响

本实验观察了Svate治疗前后17例急性心肌梗塞患者血小板聚集性和形态的影响。结果表明,Svate治疗后血小板聚集性明显下降。电镜下可见活性低的圆型和树型血小板明显增加,活性高的展平型和聚集型血小板减少。提示Svate具有降低血小板表面活性和聚集性的作用。     

粉防己碱对兔血小板聚集和血小板活化因子生成的影响(英文)

目的:探讨粉防己碱(Tet)对兔血小板聚集和PAF生成的影响.方法:卡西霉素(Cal)和PAF诱导血小板聚集的聚集率和Tet对血小板聚集的抑制率被测定;给予或未给予Tet处理之血小板用Cal刺激释放PAF的量也被测定.结果:在4—64 μmol·L~(-1)浓度范围,Tet明显抑制Cal和PAF诱导的血小板聚集.IC_(50)值分别为8.6μmol·L~(-1)和14.0μmol·L~(-1).Tet也浓度依赖性的抑制Cal诱导血小板释放PAF,IC_(50)值为21.0μmol·L~(-1).结论:Tet抑制血小板聚集作用与抑制内源性PAF生成有关.     

自体动静脉内瘘反复功能丧失患者血小板功能分析

目的:探讨维持性血液透析患者自体动静脉内瘘反复功能丧失与血小板活化及聚集功能的关系。方法:选取我院血液净化中心以自体动静脉内瘘为血管通路的血液透析患者为研究对象,分为自体动静脉内瘘反复功能丧失组(A组,18例)和自体动静脉内瘘长期存活组(B组,30例)。另设健康对照组(C组,12例)。采用流式细胞仪测定各组血小板活化指标(CD62P,CD63)的表达,同时分别以腺苷二磷酸(ADP)和花生四烯酸(AA)为诱导剂,光学法检测血小板聚集率(PAgT),并进行组间比较。结果:与内瘘长期存活组及对照组相比,内瘘反复功能丧失组的血小板活化指标(CD62P和CD63)以及血小板聚集率(PAgTADP和PAgTAA)明显增高(P<0.05或P<0.01)。Logistic回归分析显示血小板CD62P表达增加及PAgTADP增高为自体动静脉内瘘反复功能丧失的危险因素。结论:维持性血液透析患者自体动静脉内瘘反复功能丧失与其循环的活化血小板水平增高及血小板聚集功能增强相关。     

Mean platelet volume and high-residual platelet reactivity in patients receiving dual antiplatelet therapy with clopidogrel or ticagrelor

Objective: High on-treatment platelet reactivity (HRPR) is associated with a two- to ninefold increased risk of recurrent ischemic events among patients receiving dual antiplatelet therapy (DAPT) for coronary artery disease. However, its determinants are still poorly understood. The aim of the present study was to assess the impact of mean platelet volume (MPV) on platelet reactivity in patients receiving DAPT after an acute coronary syndrome or PCI.

Methods: Patients treated with DAPT (acetylsalicylic acid [ASA] and clopidogrel or ticagrelor) were scheduled for platelet function assessment at 30 – 90 days post-discharge. By whole blood impedance aggregometry, HRPR was considered for ASPI test > 862 aggregation units (AU)*min (for ASA) and ADP test values ≥ 417 AU*min (for ADP-antagonists).

Results: Our population is represented by a total of 487 patients on DAPT, divided according to MPV tertiles (< 10.4 fl; 10.4 – 11.29 fl; ≥ 11.3 fl). Larger-sized platelets were associated with use of statins (p < 0.001) and beta-blockers (p = 0.03), higher hemoglobin levels (p = 0.002) and lower platelets count (p < 0.001). Higher platelet reactivity was observed at ASPI test in patients with higher MPV (r = 0.12, p = 0.008), but not for ADP-mediated aggregation (r = -0.007, p = 0.88). However, a low prevalence of HRPR was observed with ASA, with no impact of MPV tertiles (1.2 vs 1.1 vs 1.6%, p = 0.70, adjusted OR [95% CI] = 1.05 [0.51 – 1.77], p = 0.87). MPV did not influence the prevalence of HRPR for ADP-antagonists (25.9 vs 1 vs 26.5%, p = 0.89; adjusted OR [95% CI] = 1.1 [0.84 – 1.45], p = 0.50) with similar results among the 259 patients receiving clopidogrel (adjusted OR [95% CI] = 1.15 [0.82 – 1.62], p = 0.43) and the 228 patients on ticagrelor (adjusted OR [95% CI] = 1.46 [0.84 – 2.55], p = 0.18).

Conclusion: In patients receiving DAPT, MPV does not affect the response to major antiplatelet therapies. In fact, MPV elevation does not influence the risk of HRPR with clopidogrel, ticagrelor or ASA.     

间歇服用阿司匹林预防血栓的研究

本文对１７例脑血栓形成患者给予口服阿司匹林５００ｍｇ后进行血小板功能的动态观察，结果显示：在服药后血小板的功能受到明显抑制，持续９天才恢复到服药前的水平。     

槲皮素及阿司匹林对血小板与中性粒细胞相互作用的影响

采用血小板聚集及血小板与中性粒细胞形成玫瑰花结试验探讨槲皮素及阿司匹林对血小板与中性粒细胞相互作用的影响. 结果表明,家兔中性粒细胞可抑制ADP诱导的血小板聚集,槲皮素(0.3-100 μmol·L^-1)及阿司匹林(0.4-3.3 mmol·L^-1)可增加中性粒细胞对血小板的抑制作用. 当中性粒细胞被乙酸肉豆寇佛波醇(PMA 100 μg·L^-1)激活时,此抑制作用消失. 槲皮素 (3 μmol·L^-1)可对抗PMA激活中性粒细胞. 即使无中性粒细胞存在,阿司匹林亦可抑制血小板的聚集,但单独槲皮素却不抑制血小板聚集. 槲皮素(3-300 μmol·L^-1)及阿司匹林(0.4-3.3 mmol·L^-1)可浓度相关性地抑制凝血酶激活的血小板与中性粒细胞的粘附.