冠心病患者发生阿司匹林抵抗的有关研究

目的探讨冠心病患者发生阿司匹林抵抗的概率以及相关影响因素方法79名冠心病患者服用阿司匹林（100mg/d）7天以上，分别用ADP和从作诱导剂，检测血小板聚集功能。结果用光学法（广为使用的方法）测定血小板聚集功能，阿司匹林抵抗发生率为11．4％（n=9）。阿司匹林抵抗组高血压患者的比率（44．4％）与阿司匹林敏感组（25．0％）比较有显著差别（P=0．01）。结论对服用阿司匹林的患者要检测其血小板聚集功能。高血压患者易发生阿司匹林抵抗，这提示这类患者要调整抗血小板药物，加大阿司匹林的剂量或换用其他抗血小板药物。     

业务测验(44)答案和题解

1.低浓度阿司匹林(80～160毫克/日)已可使80%血小板膜的环氧化酶被抑制,血小板产生血栓烷A_2(TxA_2)减少,血小板聚集受抑制,出血时间延长但小剂量阿司匹林不会抑制血管壁的前列环素(PGI_2)合成酶,PGI_2的生成不受限制,后者为抗血小板聚集剂。常规剂量阿司匹林(0.3克每天3次)或大剂量阿司     

心绞痛患者血小板参数及功能的变化

目的　观察冠心病心绞痛患者血小板参数及功能变化。方法　选择稳定型心绞痛 2 6例、不稳定型心绞痛 2 2例及正常者 2 6例 ,检测血小板数 (PLT)、血小板平均体积 (MPV)血小板分布宽度 (PDW)和血小板最大聚集率 (PAGM)及血浆纤维蛋白原含量 (FIB) ,并进行比较分析。结果　心绞痛患者PLT明显低于正常对照级 (P <0 .0 1 ) ,MPV、PDW、PAGM和FIB均显著高于正常对照组 (P <0 .0 5或P <0 .0 1 ) ,其中不稳定型心绞痛患者变化更甚。结论　心绞痛患者尤其是不稳定型心绞痛患者血小板消耗性下降、功能增强 ,致使平均体积和分布宽度相应增大。     

阿司匹林与氯吡咯雷联用治疗冠心病心绞痛的疗效分析

将收治的冠心病心绞痛患者82例随机分为观察组(阿司匹林+氯吡咯雷)和对照组(阿司匹林)各41例,对两组的治疗效果进行对比;两组的总有效率相比差异具有显著性(P<0.05)。观察组无一例发生不良心脏事件,对照组有2例发生不良心脏事件;阿司匹林与氯吡咯雷联用治疗冠心病心绞痛,能够有效对血小板活化功能产生抑制作用,明显改善患者心绞痛,减少不良症状的发生。     

氯吡格雷对不稳定心绞痛患者血小板功能的影响

目的探讨不稳定型心绞痛（UA）患者阿司匹林和氯吡格雷治疗前后的血小板活化状态。方法住院的UA 80例,随机分成A、B两组。检测住院当日、用药24 h后及用药7 d后CD62P、TXB2及PAGM。结果不稳定型心绞痛CD62P、TXB2和PAGM治疗前无统计学意义;治疗后B组与A组比较有统计学意义。结论在UA患者中,血小板活化起到重要作用,氯吡格雷联合阿司匹林较单用阿司匹林组抑制血小板聚集起效快;两组对抑制血小板聚集都有效,但联合用药组抑制血小板聚集作用更强。     

阿司匹林抗血小板治疗宜用小剂量

前列环素(PGl_2)具有强烈的抑制血小板聚集和扩张血管作用,而血栓素A_2(TXA_2)的作WT用刚好相反,二者之间平衡失调导致血小板与血管壁相互作用异常,这在动脉粥样硬化和冠心病的发生发展过程中起着重要作用。因此抗血小板治疗在冠心病防治中有重要的意义。阿司匹林(ASA)被广泛用于抗血小板治疗,但其合理剂量尚有争议。中国医学科学院阜外医院观察的结果如下:     

替保心脑健片对不稳定性心绞痛患者血小板活化功能的影响

现代研究表明,血小板功能异常和血栓形成是不稳定性心绞痛(ＵＡ)的病理基础和重要原因[1]。血小板活化在生理性止血或病理性血栓形成等方面起重要作用。α-颗粒膜蛋白(ＧＭＰ-140,ＧＭＰ-33)作为血小板活化释放的特异性分子标记物,其阳性表达率反映了血小板活化程度和功能状态。我们于1998年6月～1999年1月用替保心脑健片治疗ＵＡ患者50例,观察其对血小板活化功能的影响,现报道如下:1.对象与方法11　研究对象不稳定性心绞痛组。根据1979年ＷＨＯ制定的冠心病诊断标准,选取我院门诊急诊室ＵＡ患者75例,根据就诊时间按2∶1比例随机分为两组:(1…     

氯吡格雷联合阿司匹林对稳定型心绞痛合并糖尿病患者血小板聚集率及FIB水平的影响

目的 探讨氯吡格雷与阿司匹林联合使用对稳定型心绞痛合并糖尿病患者血小板聚集率及纤维蛋白原(FIB)水平的影响。方法 选取2017年4月～2020年4月我院接收的80例稳定型心绞痛合并糖尿病患者为研究对象,随机分为对照组和观察组各40例,两组均给予常规治疗,在此基础上,对照组给予口服阿司匹林,观察组给予口服阿司匹林+氯吡格雷,比较两组治疗前后血小板聚集率、FIB水平及心绞痛发作次数和时间。结果 两组治疗4周后血小板聚集率、FIB水平及心绞痛发作次数均下降,心绞痛发作时间均缩短,且观察组改善幅度优于对照组,差异有统计学意义(P0.05)。结论 氯吡格雷联合阿司匹林可显著改善稳定型心绞痛合并糖尿病患者血小板聚集率及FIB水平,减少心绞痛发作次数及发作时间,促进患者康复,值得临床推广应用。     

冠心病患者血小板参数的变化及临床意义

目的 :探讨冠心病患者血小板参数的变化及临床意义。方法 :采用COUCTER .MAXM型血细胞分析仪测定6 6例冠心病患者 [分为两组 :心绞痛组 (AP组 ) :33例 ;急性心肌梗死组 (AMI组 ) :33例 ]及 30例健康体检者 (正常对照组 )外周血中血小板计数 (PLT)、血小板平均体积 (MPV)、血小板体积分布宽度 (PDW )及血小板比容 (PCT)。结果 :AP组和AMI组MPV、PDW均明显高于对照组 (P均 <0 .0 5 ) ;AP组和AMI组PLT、PCT均明显低于对照组(P均 <0 .0 5 ) ,且MPV与PLT呈明显负相关 (r =0 .387,P <0 .0 5 )。结论 :冠心病患者血小板参数的测定 ,对其疾病的预防、诊治和预后具有一定的参考价值。     

小剂量阿司匹林对老年冠心病患者血小板活化功能的影响

目的探讨长期口服小剂量阿司匹林对老年冠心病患者血小板活化功能的影响。方法116例冠心病患者随机分为ASA50组、ASA100组及对照组,运用流式细胞仪(FCM),准确测定各组经体外二磷酸腺苷(ADP)及花生四烯酸(AA)共同活化的血小板膜表面糖蛋白(GPⅡb/Ⅲa、CD62P)的阳性表达率,观察并分析比较老年人血小板膜表面糖蛋白的阳性表达率的变化。结果(1)血小板膜表面糖蛋白GPⅡb/Ⅲa的阳性表达率在ASA50及ASA100组分别为(64.40±15.71)%,(57.22±15.82)%,两种剂量阿司匹林均较对照组(75.8±15.71)%明显降低(P<0.05)。CD62P(P-Selectin)的阳性表达率分别为(68.01±9.57)%,(60.44±9.30)%,阿司匹林组与对照组(78.59±6.38)%比较明显降低(P<0.05)。(2)ASA50组与ASA100组两组间比较,PAC-1的阳性表达率为(64.40±15.71)%与(57.22±15.82)%,两组间差异无统计学意义(P>0.05);CD62P的阳性表达率为(68.01±9.57)%与(60.44±9.30)%,两组间差异亦无统计学意义(P>0.05)。结论小剂量阿司匹林可有效抑制血小板活化功能,每日服用50mg和100mg阿司匹林对血小板活化功能的抑制无显著差异,双相激活血小板可以客观反映体内阿司匹林对血小板活化功能的影响。     

高浓度胰岛素对阿司匹林抑制的血小板中TXB2合成影响的研究

目的：探讨高浓度胰岛素是否影响阿司匹林抑制的血小板中TXB2合成。方法将制备的两组等体积的富含血小板血浆（PRP）分别加入浓度为30μU/ml和300μU/ml的胰岛素，37℃的环境下孵育3min，再次将上述两组的PRP分成等体积，分别用浓度为0、75μmol/L、150μmol/L和300μmol/L的阿司匹林处理，于37℃的环境下继续孵育30min，加入ADP 5min后，用吲哚美辛和柠檬酸葡萄糖封闭血小板反应；用血小板聚集仪检测各组的血小板最大聚集率，酶联免疫吸附法检测血小板中TXB2的含量。结果胰岛素300μU/mL组与30μU/mL组比较，前者可明显升高经阿司匹林作用后的血小板最大聚集率（P〈0.05），且明显增加血小板中TXB2的合成（P〈0.05）。结论高浓度胰岛素可减弱阿司匹林抑制的血小板TXB2合成作用。     

不同剂量阿斯匹林治疗急性脑梗死的临床分析

目的：探讨阿斯匹林（ASA）抗血栓的合理剂量。方法：对服用不同首次剂量及不同维持剂量ASA治疗201例急性脑梗死患者、34例脑梗死对照者、26名健康者进行了血浆血栓素B2、6-酮-前列腺素F1a、血小板聚集（PA）率和疗效及不良反应的动态观察。结果：首次用量300mg24hPA率、血浆血栓素B2／6－酮－前列腺素F1a比值明显低于用药前、150mg组及对照组;PA率达健康组水平,与450mg组无显著差异;维持用量100mg较50mg下降明显,PA率保持健康组水平;300／100mg、450／100mg组神经功能改善显著;450／100mg组上消化道反应、大便潜血显著增加。结论：ASA治疗急性脑梗死抗血栓快速、有效和安全,其合理量是首次300mg,维持用量是100mg／d。     

Enhanced platelet accumulation onto injured carotid arteries in rabbits after aspirin treatment.

Prostacyclin (PGI2) is a powerful inhibitor of platelet aggregation, but its role in the pathogenesis of arterial thrombosis is uncertain. We have studied the thrombogenic effect of inhibiting PGI2 production by aspirin (ASA) in carotid arteries of rabbits given 0, 3, 10, or 100 mg ASA/kg either 1, 3, 6, or 20 h beforehand. Platelet accumulation onto injured carotid arteries was enhanced with ASA in a dose of 10 mg/kg. A higher dose of ASA (100 mg/kg) had no further effect. The enhanced thrombogenic effect of ASA persisted for at least 20 h and was associated with a decrease in vessel wall PGI2 production. There was a strong inverse correlation (r = 0.55, P less than 0.01) between PGI2 production and platelet accumulation. The findings suggest that the margin of safety in obtaining an antithrombotic effect of ASA and producing a potential thrombotic effect in arteries may not be as large as predicted by studies using cultured endothelial cells or experimentally induced thrombosis in veins.     

The effect of salicylate infusion on the alveolar epithelial membrane in the isolated perfused lung

We observed two patients with aspirin (ASA) ingestion (blood levels of 87 and 56.5 mg/100 ml) who presented with noncardiogenic pulmonary edema (adult respiratory distress syndrome. To determine if ASA had a direct effect on the alveolar epithelial membrane, we established an in vitro isolated lung model and perfused it with platelet free plasma. T1/2 (in minutes), the time for 50% equilibration between the plasma and the saline filled lung, was determined before and after 500 mg salicylate infusion for various molecular weight dextrans. T1/2 decreased significantly (p less than 0.05) as follows: 3000 MW dextran, 2273 +/- 932 to 961 +/- 375; 40,000 MW dextran, 4059 +/- 1550 to 733 +/- 275; 70,000 MW dextran, 11,730 +/- 2750 to 7700 +/- 2230. Histamine levels in plasma and lung liquid did not change significantly with ASA infusion. We conclude that ASA directly increases alveolar epithelial permeability to dextrans less than 70,000 MW.     

Pharmacokinetics of enteric-coated aspirin and inhibition of platelet thromboxane A2 and vascular prostacyclin generation in humans

We evaluated whether an enteric-coated aspirin formulation showed a "presystemic" component in its antiplatelet effect and if so would spare vascular cyclooxygenase. In six healthy volunteers, 30 to 45 minutes after ingestion of 325 mg enteric-coated aspirin, platelet thromboxane A2 generation was inhibited by about 20% before any drug could be detected in the peripheral venous blood. A further decline in thromboxane A2 generation occurred with appearance of aspirin in blood between 60 and 240 minutes. No presystemic component could be detected after 325 mg aspirin tablets. Ten patients undergoing saphenectomy received 325 mg of either aspirin tablet or enteric-coated aspirin; 12 hours later platelet thromboxane A2 and peripheral vascular prostacyclin generation were significantly reduced by 98% and 58%, respectively. The effects of the two aspirin formulations were not different. Aspirin formulations with "presystemic" component in their antiplatelet effect may not necessarily result in sparing of peripheral vascular cyclooxygenase.     

Aspirin therapy for inhibition of platelet reactivity in the presence of erythrocytes in patients with vascular disease

Inhibition of erythrocyte (RBC) promotion of platelet reactivity could improve the antiplatelet effect of aspirin (ASA). We tested different ASA regimens for optimal inhibition of platelets and the effects of RBC in patients with a history of vascular diseases. Collagen-induced platelet activation (14C-5HT, TXA2 release) and platelet recruitment (proaggregatory activity of cell-free releasates from activated platelets) were measured in PRP, platelet-RBC (Hct 40%), and whole blood (WB) in 206 patients initially on 200-300-mg ASA/day. Their regimen was modified to biweekly 500 mg (loading dose, L) plus daily or twice-daily low-dose ASA (50 or 100 mg). TXA2 was inhibited with all regimens. Percentage of patients with suboptimal inhibition of platelet recruitment in WB was 200-300 ASA/day (41%), L-50/day (87%), L-100/day (58%), L-50/twice-daily (39%), and L-100/twice-daily (20%; P < 0.05 vs other regimens). 14C-5HT release was inhibited to the greatest extent with L-100/twice-daily in PRP + RBC or WB (P < 0.05 vs other regimens) due to greater inhibition of the RBC prothrombotic effect. Compared with other ASA regimens, L-100 twice-daily (equivalent to 221-mg ASA/day in the 14-day cycle), reduced by >50% the proportion of patients with suboptimal inhibition of platelet recruitment in WB and inhibited 14C-5HT release to the greatest extent.     

A new method for measuring inhibition of platelet function by nonsteroidal antiinflammatory drugs

Aspirin is widely used to help prevent vascular occlusion caused by atherosclerotic vascular disease. We used a platelet-aggregation assay (PAA) to evaluate the reliability of a proprietary platelet agonist, platelet prostaglandin agonist (PPA), to detect the amount of platelet inhibition induced by four different classes of nonsteroidal antiinflammatory drugs (NSAIDs) with antiplatelet effects. Twenty normal donors were evaluated before and 24 hours after ingestion of 325 mg of aspirin. With 125 micromol/L PPA, the slope of the PPA-PAA curve completely differentiated aspirin-treated from normal platelets. The aspirin platelet slope, 27.9 +/- 2.0 (range 5.5-47), was significantly decreased (P <.001) compared with the findings before administration of aspirin, 75 +/- 3.1 (range 50-125). Additionally, the time elapsed before 50% platelet aggregation (T(50)) with aspirin, 10.1 +/- 0.7 minutes (range 4.7-17), was significantly prolonged (P <.05) compared with the mean time before administration of aspirin (4.2 +/- 0.2 minutes, range 1.7-6.4). Aspirin in a daily dosage of 325 mg for 14 days produced significantly greater inhibition of PPA-PAA than that induced by a single 325-mg dose (P <.001). The long-term platelet-inhibitory effects of aspirin in 9 normal volunteers were evaluated with PPA-PAA 2, 8, 24, 48, 72, and 96 hours after a single dose of aspirin, 81 or 325 mg. Compared with the preaspirin slope, 79.6 +/- 1.9, the maximal decrease in slope occurred after 2 hours for both 81 mg (61.3 +/- 6.7) and 325 mg (12.1 +/- 1.8). The decreased slopes and increased T(50) observed at 2, 8, and 24 hours (P <.001) reflected the greater degree of platelet inhibition with 325 mg than with 81 mg aspirin. Inhibition of PPA-PAA was observed with nonaspirin nonsteroidal antiinflammatory drugs (NNSAIDs), but, compared with aspirin, the inhibition was minimal. PPA-PAA may be used to help measure the magnitude of NSAID-induced inhibition of platelets.     

Clinical and preclinical pharmacology of KC-764, a novel antiplatelet agent]

Preclinical pharmacological studies showed that KC-764 was more potent and more selective in inhibiting platelet aggregation than aspirin. The concentration of KC-764 for inhibiting PGI2 production in the aorta was 70 times higher than that for inhibiting TXA2 in platelets. Antiplatelet action of KC-764 was augmented by plasma components. This augmentation by plasma may lead to selective antiplatelet activity. KC-764 has been investigated for platelet function in patients with chronic cerebral infarction. KC-764 at 10, 20 and 40 mg b i d, inhibited platelet aggregation induced by arachidonic acid, collagen, and ADP, and its potency was almost equal to aspirin at 100-330 mg daily. Plasma TXB2 levels were markedly depressed by KC-764 but plasma 6-keto-PGF1 alpha levels were not influenced. On the contrary, aspirin depressed both plasma prostanoids. These findings suggest that KC-764 can overcome the 'aspirin dilemma'.     

Influence of selective thromboxane synthetase blocker CGS-13080 on thromboxane and prostacyclin biosynthesis in whole blood: evidence for synthesis of prostacyclin by leukocytes from platelet-derived endoperoxides

Increase in thromboxane A2 (TXA2) generation has been proposed as a mechanism of dynamic vaso-occlusion and in vivo platelet thrombus formation. We have examined the effects of CGS-13080, an imidazole derivative, on rabbit and human TXA2-prostacyclin (PGI2) "balance." In rabbits given CGS-13080, serum levels of TXB2 (stable metabolite of TXA2) were inhibited 81% at 2 hours and 56% at 24 hours (both P less than or equal to 0.01). Collagen-induced platelet aggregation was inhibited at 2 hours after CGS-13080 administration. In contrast, serum levels of 6-keto-PGF1 alpha (stable hydrolysis product of PGI2) increased 587% compared with control values at 2 hours (P less than or equal to 0.01). Platelet and white blood cell counts were not significantly altered. In human blood incubated in vitro with CGS-13080, serum TXB2 was completely inhibited, whereas PGI2 generation was stimulated (both P less than or equal to 0.001). In other experiments, we demonstrated uptake of platelet-generated cyclic endoperoxides by leukocytes and generation of PGI2 in the presence of CGS-13080 but not indomethacin. Thus, CGS-13080 inhibits TXA2 and stimulates PGI2 production in rabbit and human blood. Increase in PGI2 generation with TXA2 inhibition may be of potential benefit in conditions characterized by platelet hyperactivity.     

Comparison of collagen versus adenosine diphosphate in detecting antiplatelet effect in patients with coronary artery disease

Widely varying methods of assessing platelet aggregation have resulted in the absence of an established standard approach to assess the effects of antiplatelet drugs. The objective of this study was to compare the roles of collagen and adenosine diphosphate (ADP) in the assessment of effects of aspirin or clopidogrel on platelet aggregation. Sixty patients with documented coronary artery disease were assigned to receive aspirin alone (ASA 100 mg/d) (n = 30) or aspirin-plus-clopidogrel (ASA 100 mg/d + C 75 mg/d) (n = 30). Platelet aggregation assessment by the use of whole blood aggregation tests with collagen or ADP was performed in these patients and 30 age- and gender-matched normal volunteers. When compared with the control group, therapy with ASA or ASA + C resulted in significant inhibition of collagen-induced platelet aggregation (P < 0.001 for each), but there was no statistically significant difference in the results between the ASA and ASA + C groups. When platelet aggregation was induced by ADP, the combined therapy with aspirin and clopidogrel decreased platelet aggregation significantly when compared with aspirin alone (P < 0.001), and no significant difference in the results between the ASA and normal groups was observed. In conclusion, collagen may prove useful to study the effect of aspirin and ADP may be appropriate for assessing the inhibitory effect of clopidogrel.