Leucocyte aggregation in acute cerebrovascular disease

We evaluated leucocyte aggregation in 26 patients with ischemic stroke and in 10 patients with transient ischemic attacks (TIA), previously untreated, within 24 h from the onset of symptoms. The evaluation was also performed in 30 healthy subjects matched for age and sex. Leucocyte aggregation was significantly higher in patients than in controls (p < 0.01 post hoc Tukey test). Within patients, those with stroke showed a significantly higher aggregation than those with TIA (p = 0.01 post hoc Tukey test). Moreover, stroke patients with the poorest outcome showed significantly higher values of leucocyte aggregation. These results indicate an involvement of leucocytes in cerebral ischemia and suggest that changes in their aggregability may play a role in the evolution of the disease.     

Platelet aggregation in transient global amnesia

We found a correlation between increased platelet aggregation parameters and transient global amnesia and no differences between patients with transient global amnesia and transient ischemic attacks. Our findings support the theory of a vascular mechanism for transient global amnesia. Note. A preliminary form of the present work was presented at the Xth International Congress on Thrombosis and Haemostasis in San Diego, California, July 14–19, 1985.     

Comparison between induced platelet aggregation and circulating platelet aggregates as platelet function tests in patients with transient ischemic attacks

Routine blood analysis, platelet counts, number of circulating platelet aggregates (CPA) and platelet aggregation in vitro against adenosine-diphosphate (ADP), epinephrine and collagene were studied in 45 healthy controls, in 10 hospitalized patients with other neurological diseases than stroke and in 12 patients with transient ischemic attacks (TIA) before and after prophylactive treatment with anticoagulants (AC) or anti-platelet drugs (APD).
Except for lower hemoglobin and hematocrit levels in women, sex, smoking, oral contraceptives or pregnancy did not significantly influence the routine blood parameter. Smoking females taking oral contraceptives had an increased number of CPA and the most easily induced aggregation in vitro .
Patients with TIA had no significant differences in blood or platelet findings versus the healthy controls (except smoking females on oral contraceptives) or the non-stroke patients, even though individual patients could have high numbers of CPA and an easily induced platelet aggregation in vitro . Treatment with AC did not influence platelet function, whereas APD therapy decreased the number of CPA and inhibited the secondary platelet aggregation in vitro .     

缺血性脑血管病常用药物对血小板聚集功能的影响

应用比浊法测定了川芎嗪，刺五加，维脑路通，潘生丁，阿斯匹林对２０例脑梗塞病人和１２例健康人的血小板聚集功能的影响。结果显示：不论是正常人还是脑硬塞病人，这些药物在体外都能抑制血小板聚集。其中川芎嗪对血小板聚集抑制作用最强，维脑路通作用最弱。     

Intravascular microaggregation and in vitro platelet aggregation in coronary artery disease

The amount and protein composition of heparin precipitable fraction (HPF), and the plasma concentrations of fibrinogen, fibronectin, alpha 1-acid glycoprotein, alpha 1-antitrypsin, haptoglobin and C-reactive protein (CRP) were determined in healthy subjects as well as during the course of acute myocardial infarction (AMI). In all samples tested, HPF consisted nearly exclusively of fibrinogen and fibronectin. In the small precipitates from healthy subjects, approximately equal amounts of these two proteins were recovered. During the first days of AMI, plasma fibrinogen increased 2-3 fold. At the same time, however, the amount of HPF increased 5-10 fold. This increase was associated with increased precipitation of fibrinogen, whereas no simultaneous increase in fibronectin was found. In fact, a slight drop in plasma as well as HPF-fibronectin was regularly observed during this period. During the following week HPF returned to normal values, whereas the plasma fibrinogen remained elevated. No satisfactory explanation for this discrepancy can be offered at present. Thus, no evidence could be provided that other acute phase proteins than fibrinogen itself were involved. Some experiments, however, indicated qualitative changes in the fibrinogen participating in the HPF precipitation. Further studies are necessary to clarify this point. Such studies are in progress.     

脑血管血液动力学指标对颈动脉系统TIA的诊断价值

目的　探讨脑血管血液动力学指标 (CVDI)对颈动脉系统 TIA的诊断价值。方法　对 32例颈动脉系统短暂性脑缺血发作 (TIA)患者进行脑循环动力学检测仪 (CVA)检测 ,并与健康对照组比较。结果　 87.5 %的患者病侧 CVDI异常 ,表现为脑血流下降、外周阻力增高、微循环障碍。结论　颈动脉系统 TIA存在不同程度的脑血管血液动力学改变 ,CVDI可作为颈动脉系统 TIA实验室诊断的敏感指标。     

缺血性脑卒中和短暂性脑缺血发作患者氯吡格雷抵抗及其影响因素分析

目的观察北方汉族人群缺血性脑卒中及短暂性脑缺血发作(TIA)患者氯吡格雷抵抗的发生率,并分析可能相关的影响因素。方法共入选104例接受氯吡格雷75 mg·d-1治疗的动脉粥样硬化性脑梗死及TIA患者,于治疗前及治疗后第7天,应用比浊法检测腺苷二磷酸诱导的血小板聚集率。以血小板聚集率下降≤10%为划界,分为氯吡格雷抵抗(CR)组37例(35.58%)和非氯吡格雷抵抗(NCR)组67例(64.42%)。采集两组患者的病史及临床资料,进行统计学分析。结果 CR组合并2型糖尿病和高血压病的患病率高于NCR组(分别P=0.024,P=0.008);CR组血清胆固醇水平和体重指数(BMI)高于NCR组(分别P=0.040,P=0.013)。多因素Logistic回归分析提示BMI≥28 kg/m2与氯吡格雷抵抗可能具有相关性(OR=3.600,95%CI:1.110~11.678,P=0.033)。结论 BMI≥28 kg/m2可能为缺血性脑卒中及TIA患者发生氯吡格雷抵抗的危险因素     

Platelet aggregation in focal cerebral ischemia – a clinical study

In a consecutive series of 35 patients with transient ischemic attacks (TIAs) 26 patients (74%) had pathological platelet aggregation 4 weeks after the latest TIA. Pathological platelet aggregation was the most frequent factor leading to a prophylactic treatment of the TIAs. Among 12 patients with reversible ischemic neurological deficit (RIND) only one had pathological platelet aggregation, and among 54 patients with completed stroke 37% had pathological platelet aggregation 4 weeks after the cerebral infarction.
It is possible by the antiaggregating agents acetylsalicylic acid and dipyridamole to normalize in vitro pathological platelet aggregation. The frequency of side effects was low. During this treatment further TIAs were stopped in 17/19 patients, and remission were seen in 14/14 stroke patients. Compared with the remissions during treatment with anticoagulants there was a tendency of more favouarble outcome in the group of stroke patients when treated with antiaggregating agents.     

The erythrocyte adhesiveness/aggregation test in the peripheral blood of patients with ischemic brain events

We adopted a simple slide test and image analysis to determine the state of erythrocyte adhesiveness/aggregation in the peripheral blood of 45 patients with acute ischemic stroke, 30 with TIA and 27 matched controls. A highly significant (P=0.005) difference was noted between patients and controls regarding the degree of erythrocyte adhesiveness/aggregation while there was no significant difference for both erythrocyte sedimentation rate or fibrinogen concentrations. We suggest that our slide test might be a low cost and real time method to detect the increased erythrocyte aggregability in the peripheral blood of patients with acute ischemic neurological events. These findings might be relevant in view of recent studies that suggest a favorable effect of therapeutic interventions directed at the improvements of this hemorrheological aspect in individuals with ischemic vascular conditions.     

微栓子信号监测评估抗小板聚集药和他汀类药物联用治疗急性缺血性脑卒中疗效的研究

目的应用微栓子信号(MES)监测评估抗血小板聚集药和他汀类药物联用治疗急性缺血性脑卒中的疗效。方法 62例急性缺血性脑卒中患者随机分为两组:两联治疗组(30例,采用氯比格雷加阿司匹林治疗)和瑞舒伐他汀组(32例,采用氯比格雷、阿司匹林及瑞舒伐他汀治疗)。分别在治疗前及治疗后第3d、第7 d和第14 d采用TCD监测MES。比较两组MES监测结果。结果与治疗前相比,两组治疗后第3 d、第7 d和第14 d的MES数量均明显下降(均P0.05)。治疗后第3 d、第7 d和第14 d,瑞舒伐他汀组MES数量较两联治疗组明显下降(均P0.05)。瑞舒伐他汀组治疗后第3 d、第7 d和第14 d的MES下降率均明显高于两联治疗组(均P0.05)。结论两联抗血小板聚集药联用他汀类药物治疗急性缺血性脑卒中相较于单用两联抗血小板治疗可以取得更好的疗效。     

Platelet arachidonic acid metabolism in severe cerebrovascular disease

The ability of platelets to synthetise thromboxane B₂ and hydroxylated fatty acids from arachidonic acid was studied simultaneously with arachidonic acid-induced aggregation in 42 patients suffering from severe cerebral atherosclerosis and also in 34 healthy controls. Additionally, phospholipase-A₂-induced aggregation was performed as a probe for arachidonic acid located at the platelet surface. All the assays were performed with washed platelets, eliminating a possible influence of plasma. Platelets from patients were found responsive to significantly lower concentrations of arachidonic acid whereas thromboxane and hydroxylated fatty acid biosynthesis did not differ from controls. In the experimental conditions used, 75% of the control platelets underwent aggregation with phospholipase A₂ plus sphingomyelinase C, in comparison to only 50% for the patients, indicating the necessity for further analysis of the platelet membrane lipids in atherosclerosis.     

The effects of the second generation antipsychotics and a typical neuroleptic on collagen-induced platelet aggregation in vitro

Objective. Antipsychotics are widely used in psychiatry, and consequently a lot of their side effects have been reported. One of them is cardiovascular disease leading to increased risk of stroke, thrombosis, pulmonary, embolism, in which hyperactivation of blood platelets is involved. The purpose of the present study was to examine the effects of the second generation antipsychotics (SGAs) such as clozapine, risperidone, and olanzapine, and a typical neuroleptic – haloperidol – on the one step of platelet activation–platelet aggregation induced by collagen in vitro. Blood was collected into buffered sodium citrate (3.8%) and centrifuged to get platelet-rich plasma (PRP). In PRP (2×10⁸ platelets/ml) obtained from healthy volunteers that was incubated with antipsychotics (clozapine, risperidone, olanzapine, haloperidol; 30 min) aggregation of blood platelets was measured using a Chrono-Log Lumi-aggregometer. Aggregation of platelets was measured after stimulation of platelets with 1 µl of collagen (2 µg/ml). Results. Clozapine, like haloperidol reduced platelet aggregation induced by collagen (inhibition of platelet aggregation reached about 20%) (P=1×10^?5 and P=0.003, respectively). Risperidone had also a weak antiaggregatory effect (P=0.05). Among tested antipsychotics only olanzapine had no effect on collagen-stimulated platelet aggregation (P>0.05). Conclusion. The obtained results indicate that the difference in action of tested drugs on platelet aggregation may dependent on the various chemical structures of these drugs. Clozapine, risperidone and haloperidol are structurally diverse, and they all significantly reduce platelet aggregability induced by collagen. On the other hand, a close structural analog of clozapine – olanzapine – did not inhibit platelet aggregation. However, mechanism of antipsychotics action on blood platelets is not clear. Moreover, it seems that clozapine, risperidone and haloperidol treatment due to antiaggregatory action may have even some antithrombotic effects.     

Inhibition of human platelet aggregation by vitamin K

The effect of several vitamin K (Vit K) analogues on the aggregation of human platelets was examined. The analogues were potent inhibitors of aggregation induced by ADP, thrombin, collagen and arachidonate but were less active against aggregation induced by the calcium ionophore A23187. Vit K3 also prevented platelet membrane phosphatide breakdown induced by collagen. These effects were not due to a direct inhibition of enzymes involved in the liberation of arachidonate or its subsequent transformation. The analogues exerted no effects on enzymes regulating intraplatelet cAMP. However, these effects could be overcome by increasing extracellular Ca++ levels, indicating a possible interaction with Ca++ regulation in platelets.     

A study of intravascular platelet aggregation by continuous platelet counting

Intravascular platelet aggregation has been studied by measuring the response to aggregating agents using continuous platelet counting. Dose-dependent falls in platelet count occurred after the injection of collagen, prostaglandin H₂ (PGH₂), arachidonic acid (AA) and four synthetic prostanoids in rats. Indomethacin partially inhibited collagen- and AA-induced aggregation in the rat and collagen-induced aggregation in the rabbit. Indomethacin and aspirin did not produce a dose-dependent inhibition of collagen-induced aggregation over the range of doses tested. 1-n-butylimidazole inhibited collagen- and PGH₂-induced aggregation in the rabbit but did not inhibit collagen- or AA-induced aggregation in the rat.     

Endotoxin-mediated inhibition of human platelet aggregation

A variety of endotoxins, when added to human platelet-rich plasma (PRP) or to suspensions of washed platelets (WP), demonstrated an inhibitory effect on platelet aggregation induced by various aggregating agents. Endotoxin blocked the release of 14C serotonin from platelets but had no influence on cyclic AMP production. Endotoxin did not interfere with thromboxane generation by platelets. However, endotoxin-treated platelets failed to respond to added thromboxane. The inhibitory effect of endotoxin on platelet aggregation was more pronounced in the presence of ionophore A23187 as compared to other aggregating agents and was effectively reversed by calcium but not by magnesium, another divalent cation. Furthermore, endotoxin failed to inhibit the ristocetin-induced agglutination of formaldehyde-fixed platelets; a non-calcium dependent phenomenon. These findings appear to suggest that endotoxin-mediated inhibitory activity of platelet aggregation is related to the interference in the role of calcium. The antiaggregatory activity of endotoxin appears to be due to a direct and rapid action on platelets and not due to a non-specific binding, as the effect was not abolished by washing the endotoxin-incubated platelets. Endotoxin-mediated alteration of platelet function may contribute to bleeding diathesis in septecemic and endotoxemic patients.