缺血性脑血管病患者血浆D－二聚体和GMP－140含量的变化及临床意义

用ＥＬＩＳＡ双抗体夹心法和放射免疫法对７３例缺血性脑血管病患者血浆Ｄ－二聚体、血小板表面及血浆ＧＭＰ－１４０含量进行了测定。结果显示脑血栓形成（ＣＩ）急性期、恢复期和短暂性脑缺血发作（ＴＩＡ）患者血浆Ｄ－二聚体、血小板表面和血浆ＧＭＰ－１４０的含量均明显高于正常对照组（Ｐ＜０．００１）。ＴＩＡ伴有梗塞灶者无论血浆Ｄ－二聚体的含量还是血小板表面和血浆ＧＭＰ－１４０含量均显著高于无梗塞灶者（Ｐ＜０．０５，Ｐ＜０．００１，Ｐ＜０．０５）。结果提示缺血性脑血管病患者体内血液凝固性增强和血小板活化亢进。不仅对进一步了解缺血性脑血管病的发病机理和治疗提供了理论根据，而且对于观察病情演变、判断预后均有重要的临床意义     

抗血小板药物对造影阴性蛛网膜下腔出血病人颅内出血的影响

目的 探讨抗血小板药物与造影阴性蛛网膜下腔出血（NaSAH）病人出血量及出血进展的关系。方法 回顾性分析2009年5至2022年3月收治的62例NaSAH的临床资料。结果24例入院前有抗血小板药物治疗史（观察组）,36例无抗血小板药物治疗史（对照组）。观察组16例服用阿司匹林,10例服用氯吡格雷,2例服用双抗治疗,抗血小板药物使用时间平均（11.4±3.8）个月。观察组出血量[（13.8±6.3）ml]明显高于对照组[（8.7±4.6）ml;P<0.05]。观察组出血扩展率（45.8%）高于对照组（23.7%;P=0.069）。结论 抗血小板药物使用与NaSAH颅内出血量增加、出血扩展有关。     

缺血性脑血管病患者血浆内皮素的研究

本文测定了６０例缺血性脑血管病患者血浆内皮素水平，并与１４例正常人对照。结果发现：脑血栓形成急性期患者血浆内皮素升高（Ｐ＜０．０１），而且其浓度与梗塞灶体积大小呈正相关；脑动脉硬化症组血浆内皮素水平也高于正常对照组（Ｐ＜０．０５）；既往有高血压病史的患者血浆内皮素高于无高血压病史者（Ｐ＜０．０５），说明内皮素可能在缺血性脑血管病的发生和发展中具有一定作用，并可能作为病情预后的指标之一。     

长期口服抗血小板药物合并急性硬膜下血肿的临床分析

目的分析长期口服抗血小板药物合并急性硬膜下血肿（ASDH）患者的临床治疗策略及疗效。 方法回顾性分析解放军联勤保障部队第九〇一医院神经外科自2018年1月至12月手术治疗的ASDH患者67例。口服抗血小板药物者32例，其中服用阿司匹林者（单抗组）20例，服用阿司匹林+氯吡格雷药物者（双抗组）12例，未服用抗血小板药物者（对照组）35例。对比分析3组患者术前凝血指标、术中失血量、术后硬膜外引流量、再出血及二次手术率等指标，所有患者随访6个月以上，对比分析3组患者的GOS评分和改良Rankin量表（mRs）评分。 结果与对照组相比，单抗组与双抗组的出血时间、双抗组的部分凝血活酶时间显著延长，且术中出血量及术后硬膜外引流量均显著增多，差异均有统计学意义（P<0.05）。单抗组3例（15.00%）、双抗组4例（33.33%）及对照组1例（2.86%）术后发生再出血行二次手术。随访6个月以上，单抗组与双抗组的GOS评分及mRs评分较低，恢复良好率较对照组显著降低（P<0.05）。 结论长期口服抗血小板药物药物可加重ASDH的病情，术中止血困难、出血多，术后再出血率高，降低了远期神经功能恢复。     

溶血磷脂酸和氧化低密度脂蛋白的相关性分析及与缺血性脑血管病早期的关系

目的 探讨溶血磷脂酸（LPA）和氧化低密度脂蛋白（ox—LDL）的相关性，进一步研究二者在缺血性脑血管病中的变化，揭示其在缺血性脑血管病早期的预警作用。方法 随机选择62例患者，根据病情将其分为急性脑梗死早期（CI）组30例，短暂脑缺血发作组（TIA）32例，并选30例健康人作为对照组，分别用ELISA法测定氧化低密度脂蛋白（ox—LDL），用有机溶剂抽提法测定溶血磷脂酸（LPA）。检测结果进行统计学分析。结果 急性脑梗死早期组和短暂脑缺血发作组血浆中LPA和ox—LDL水平显著高于对照组（P〈0，05），短暂脑缺血发作组与急性脑梗死早期组相比，短暂脑缺血发作组血浆中LPA水平较高（P〈0．05）。急性脑梗死早期组和短暂脑缺血发作组血浆中LPA和ox—LDL之间比较呈显著正相关（P〈0．05）。结论 在缺血性脑血管病早期血浆中LPA和ox—LDL活性增高，且二者之间呈显著正相关，短暂脑缺血发作组血浆中LPA水平较急性脑梗死早期组增高，LPA作为体内凝血和血栓形成过程早期释放的分子标记物，在预测缺血性脑血管病的发生发展，及指导合理应用抗血小板及抗凝药物方面可能有一定应用前景，ox—LDL与缺血性脑血管病的发病也密切相关。     

阿司匹林对缺血性脑血管病患者抗血小板聚集作用的临床观察

阿司匹林是抗血小板聚集药物，广泛应用在心脑血管疾病的治疗和预防。本研究对日服阿刮匹林75mg的68例缺血性脑血管病（ICVD）患者通过测定其血小板聚集率观察阿司匹林的抗血小板聚集作用。     

长期服用小剂量阿司匹林不能降低急性缺血性脑卒中的严重性

目的评价长期服用小剂量阿司匹林对急性缺血性脑血管病严重程度的影响.方法将321例急性缺血性脑血管病患者根据发病前是否服用阿司匹林进行随机分组和病例配对研究,临床评分作为病情严重程度的指标.结果随机分组和病例配对中,服药组临床评分为17.39±9.90,未服药组为16.22±9.98,两组比较,差异无显著意义.结论长期服用小剂量阿司匹林不能降低急性缺血性脑血管病的严重程度.     

噻氯匹定治疗TIA疗效观察

我科自１９９７年１０月至１９９９年２月应用噻氯匹定治疗血小板聚集率增高的ＴＩＡＡ患者３１例，并设对照组应用曲克芦丁治疗，对临床疗效和服药前后的血小板聚集率进行了对比观察，现报告如下：１对象和方法１．１观察对象根据１９８６年全国第二次脑血管病学术会议通过的短暂性脑缺血发作（ＴＩＡ）的诊断标准［１］，确诊的ＴＩＡ患者，全部行血小板聚集率检查，将其中５９例血小板聚集率增高者，按入院先后分为噻氯匹定治疗组（观察组）和曲克芦丁治疗组（对照组）。所有患者经脑ＣＴ或磁共振检查，未发现出血或缺血性病灶。观察组３…     

中国缺血性脑卒中患者抗血小板药物的应用现状

目的探讨中国缺血性脑卒中(IS)患者抗血小板类药物的使用现状及影响用药的相关因素。方法对我国北方和中、东部14个城市的病程>3个月的IS患者的基本资料及服用抗血小板类药物的情况进行调查和分析。结果共有6422例IS患者被调查,均有服用抗血小板药物的适应证,但仅有72.4%患者(4652例)服用抗血小板药物;其中98.7%服用阿司匹林;IS≥3年的患者服药率(64.0%)明显低于IS<1年的患者(72.0%)(P<0.001);合并冠心病、高血压的患者服药率明显高于无此类合并症的患者(均P<0.001)。结论中国IS患者抗血小板药物使用现状与IS二级预防指南推荐的均应服用抗血小板药物的要求存在明显的差距,尤其是病程较长的IS患者。     

408例缺血性脑血管病二级预防抗血小板药物应用状况调查

目的 了解北京市部分二级医院缺血性脑血管病二级预防抗血小板药物的应用现状,为改进缺血性脑血管病二级预防工作提供依据.方法 本研究为现况调查,研究对象为以自愿形式参加的北京市4家二级医院中急性脑梗死及短暂性脑缺血发作(TIA)的住院患者,调查其住院期间以及出院3个月二级预防抗血小板药物的应用现况.结果 人选患者共458例.其中408例完成3个月随访.住院期间抗血小板药物应用率为93.7%,3个月随访发现.抗血小板药物的院外治疗依从性差,应用率明显下降,为69.6%(P=0.003);男性(OR=1.708),95%CI 1.083～2.691及TIA患者(OR=1.954,95%CI1.046～3.649)成为患者抗血小板药物依从性差的促进因素.结论 北京市部分二级医院缺血性脑血管病二级预防抗血小板药物的应用现状不容乐观,临床医生应对缺血性脑血管病患者二级预防抗血小板药物的依从性给予关注.     

Effect of chronic antiplatelet treatment on platelet activating factor-induced platelet activity in stroke

The effect of chronic antiplatelet treatment on PAF--induced platelet aggregation, ATP--release, and cytoplasmic ionized calcium was studied in 20 acute ischemic stroke patients. Chronic antiplatelet treatment failed to suppress these PAF--induced platelet responses. We speculate that selective PAF antagonists may be useful in suppressing PAF--induced platelet activation, and thereby possibly improve the treatment of stroke.     

Non-activated platelet cytoplasmic ionized calcium in patients with acute ischemic stroke and healthy controls]

Non-activated platelet cytoplasmic ionized calcium was measured in Aequorin-loaded Gel-filtered platelets in 43 patients with acute ischemic stroke and 32 healthy controls. Platelet cytoplasmic ionized calcium is 2,596 +/- 0,674 mumol/L in controls, 3,370 +/- 1,339 mumol/L in the patients with acute ischemic stroke. Platelet cytoplasmic ionized calcium is increased in the stroke patients as compared to controls (P < 0.01). This indicates that there may be a lower threshold in platelet of stroke patient for activation. Moreover, increased platelet cytoplasmic ionized calcium may be a risk factor for thrombus propagation and aggravation of clinical manifestation.     

Pharmacological Difference Between Platelet Aggregations in Cardioembolic Stroke Patients with Direct Oral Anticoagulants: A Pilot Study

Background Selecting the appropriate direct oral anticoagulants (DOACs) for embolic ischemic stroke patients, especially on concurrent antiplatelet therapy, is important. However, a limited number of studies have reported on the pharmacological differences in platelet aggregation of each DOAC. We aimed to evaluate the antiplatelet effects of selected DOACs, by comparing dabigatran (a direct oral thrombin inhibitor) and factor Xa (FXa) inhibitors (apixaban and rivaroxaban) in patients who had suffered a cardioembolic stroke.Methods We retrospectively evaluated 12 patients diagnosed with a cardioembolic stroke who took any DOAC without an antiplatelet drug and underwent platelet aggregation tests within 60 days from the onset of symptoms. The platelet aggregation tests were analyzed by both light transmission aggregometry and VerifyNow®.Results Six patients (50%) took dabigatran, while the other six (50%) took an FXa inhibitor (n = 4 for apixaban and n = 2 for rivaroxaban). From the light transmission aggregometry analysis, it was found that the maximal extent of aggregation for adenosine diphosphate (ADP) was significantly higher with dabigatran than with FXa inhibitors, and the ED₅₀ value of ADP on platelet aggregation was significantly lower with dabigatran than with FXa inhibitors. Moreover, the VerifyNow® analyses revealed that P2Y₁₂ reaction units were significantly higher with dabigatran than with FXa inhibitors.Conclusions Dabigatran had little impact on platelet aggregation compared to FXa inhibitors in patients who had suffered a cardioembolic stroke with atrial fibrillation, and who took DOACs for secondary prevention within 60 days from the onset.     

Effect of sarpogrelate, a 5-HT(2A) antagonist, on platelet aggregation in patients with ischemic stroke: clinical-pharmacological dose-response study

BACKGROUND AND PURPOSE: It is widely accepted that antiplatelet therapy is effective for secondary prevention of atherosclerotic vascular diseases. We performed a double-blind, controlled clinical-pharmacological study to investigate the antiplatelet efficacy of sarpogrelate, a selective 5-hydroxytryptamine (5-HT(2A)) receptor antagonist, in patients with ischemic stroke, using a new assessment system employing combinations of 5-HT and epinephrine as agonists. METHODS: Forty-seven patients with ischemic stroke were randomly assigned to three groups: 15 patients received 25 mg sarpogrelate (group L), 16 patients received 50 mg (group M), and 15 patients received 100 mg (group H) orally, three times daily for 7 days. The effect was expressed as maximum intensity of platelet aggregation on the last day of medication. Two combinations of agonists, 0.5 micromol/l 5-HT plus 3 micromol/l epinephrine, and 1 micromol/l 5-HT plus 3 micromol/l epinephrine, were used to induce platelet aggregation. RESULTS: With both combinations of agonists, sarpogrelate treatment inhibited platelet aggregation dose-dependently (p < 0.025, Jonckheere test). In multiple-group comparison, the effect in group H was greater than that in group L or M (p < 0.025, Wilcoxon rank-sum test). CONCLUSION: Sarpogrelate treatment inhibited platelet aggregation dose-dependently in patients with ischemic stroke, as judged by a new assessment system employing combinations of 5-HT and epinephrine as agonists.     

Dual Antiplatelet Therapy after Noncardioembolic Ischemic Stroke or Transient Ischemic Attack: Pros and Cons

Dual antiplatelet therapy simultaneously blocks different platelet activation pathways and might thus be more potent at inhibiting platelet activation and more effective at reducing major ischemic vascular events compared to antiplatelet monotherapy. Aspirin plus clopidogrel dual therapy is now the standard therapy for patients with acute coronary syndrome and for those undergoing percutaneous coronary intervention. However, dual antiplatelet therapy carries an increased risk of bleeding. Patients with ischemic stroke or transient ischemic attack (TIA) are generally older and likely to have a fragile cerebrovascular bed, which further increases the risk of systemic major bleeding events and intracranial hemorrhage. Clinical trials and meta-analyses suggest that in comparison to antiplatelet monotherapy, dual antiplatelet therapy initiated early after noncardioembolic ischemic stroke or TIA further reduces the rate of recurrent stroke and major vascular events without significantly increasing the rate of major bleeding events. In contrast, studies of long-term therapy in patients with noncardioembolic ischemic stroke or TIA have yielded inconsistent data regarding the benefit of dual antiplatelet therapy over monotherapy. However, the harm associated with major bleeding events, including intracranial hemorrhage, which is generally more disabling and more fatal than ischemic stroke, is likely to increase with dual antiplatelet therapy. Physicians should carefully assess the benefits and risks of dual antiplatelet therapy versus antiplatelet monotherapy when managing patients with ischemic stroke or TIA.     

Multiple electrode aggregometry in antiplatelet-related intracerebral haemorrhage

As the population ages, antiplatelet agents are increasingly used in patients with cardiovascular diseases. Due to impaired platelet activity, these patients are at increased risk for bleeding complications and this is of particular importance in patients with intracerebral haemorrhage. The multiple electrode aggregometry analyser Multiplate (Roche Diagnostics, Mannheim, Germany) was introduced in 2006 to monitor the effectiveness of antiplatelet drugs in interventional cardiology. As a point-of-care device, it allows bedside assessment of platelet activity within minutes through analysis of a sample of whole blood. In patients treated with antiplatelet medication and in need of urgent cardiac surgery, these devices allow prediction of intraoperative blood loss and their use was implemented within respective guidelines to direct transfusion strategies. We used the Multiplate analyser for rapid assessment of antiplatelet activity in a patient who developed an intracerebral haemorrhage after administration of aspirin and clopidogrel. Antiplatelet activity was assessed within 10 minutes while the patient was transferred to the operating room and after transfusion of platelet concentrates and administration of desmopressin and tranexamic acid, repeated Multiplate analysis demonstrated nearly normalized platelet activity. In our view, there is great potential for this device to improve treatment in neurosurgery and especially the treatment of antiplatelet-related intracerebral haemorrhage. Instant assessment of antiplatelet activity or effectiveness of haemostatic measures is facilitated and furthermore, patients with normal platelet activity despite a positive history of antiplatelet medication intake can be identified. In these patients, empiric administration of haemostatic substances would unnecessarily increase the risk of thromboembolic events.     

Piracetam versus acetylsalicylic acid in secondary stroke prophylaxis. A double-blind, randomized, parallel group, 2 year follow-up study

Piracetam has been shown to inhibit platelet aggregation. Therefore, we performed a double-blind, randomized, parallel group study to compare the efficacy of daily 1600 mg piracetam t.i.d. vs. 200 mg acetylsalicylic acid (ASA) t.i.d. in secondary stroke prophylaxis. 563 patients after stroke as confirmed by computed tomography (CT) or magnetic resonance imaging (MRI) were enrolled and received either piracetam or ASA during a 2 year follow-up period. The primary endpoint was the rate of stroke, transient ischaemic attack (TIA), or death from vascular cause. The secondary endpoint was the rate of adverse events leading to a premature discontinuation of the study medication. Patients were visited at home every 3 months and were examined in hospital after 1 and 2 years. At every visit, the platelet function was evaluated. No significant difference and no significant equivalence could be shown for the primary endpoint between the piracetam and the ASA group both in the intention-to-treat and in the per-protocol analysis. However, there was a not significant trend in favor of ASA (11.7 vs. 15.2%). After excluding those patients who did not respond to antiplatelet medication in vitro, however, piracetam and ASA were equivalent in secondary stroke prophylaxis (stroke, TIA, or vascular death 10.1% in the piracetam group vs. 9.7% in the ASA group). Piracetam was significantly superior to ASA in the secondary endpoint (P=0.0039). The data suggest that the overall efficacy of piracetam in secondary stroke prophylaxis is not as good as that of ASA but that piracetam is better tolerated. However, our data furthermore show that nonresponders to pharmacological inhibition of platelet function are more frequent under piracetam therapy and that they may influence the results of large studies on secondary prophylaxis in vascular diseases.     

Antiplatelet resistance in stroke

Although the exact prevalence of antiplatelet resistance in ischemic stroke is not known, estimates about the two most widely used antiplatelet agents - aspirin and clopidogrel - suggest that the resistance rate is high, irrespective of the definition used and parameters measured. Inadequate antiplatelet responsiveness correlates with an increased risk of recurrent ischemic vascular events in patients with stroke and acute coronary syndrome. It is not currently known whether tailoring antiplatelet therapy based on platelet function test results translates into a more effective strategy to prevent secondary vascular events after stroke. Large-scale clinical trials using a universally accepted definition and standardized measurement techniques for antiplatelet resistance are needed to demonstrate whether a 'platelet-function test-guided antiplatelet treatment' strategy translates into improved stroke care. This article gives an overview of the clinical importance of laboratory antiplatelet resistance, describes the challenges for platelet-function test-guided antiplatelet treatment and discusses practical issues about the management of patients with aspirin and/or clopidogrel resistance.     

Initial experiences with Multiplate for rapid assessment of antiplatelet agent activity in neurosurgical emergencies

Objective

As the population ages, physicians encounter a growing number of patients who are treated with antiplatelet agents and present with severe conditions requiring urgent neurosurgical therapy. Standard laboratory investigations are insufficient to evaluate platelet activity and furthermore, it is difficult to evaluate effects of haemostatic measures on platelet function. In this article we report our initial experiences with the point-of-care device Multiplate^® for assessment of platelet activity in neurosurgical emergencies on patients with a reported intake of antiplatelet medication.

Methods

Multiplate^® assessment of antiplatelet activity was carried out in 21 non-consecutive patients with a reported intake of antiplatelet medication (aspirin: n = 21, clopidogrel: n = 3, ticragrelor: n = 1) and urgent admission to our hospital because of conditions such as intracranial haemorrhage requiring urgent neurosurgical therapy. Analysis was repeated in order to evaluate the effectiveness of haemostatic drugs and platelet concentrate transfusion on platelet activity in six patients.

Results

No technical difficulties occurred and in all cases, results were obtained within 15 min. On admission, patients’ arachidonic acid induced platelet activity was reduced by 44.4 ± 33.5% (range: −79.7% to +44.3%) compared to the lower reference limit. Two patients had a normal platelet activity despite a reported intake of aspirin. Haemostatic measures significantly increased arachidonic acid induced platelet activity by 100 ± 66% (p < 0.005).

Conclusion

The Multiplate^® device allowed rapid assessment of antiplatelet agent activity and evaluation of haemostatic measures on platelet activity. Further studies with larger patient numbers are needed, but this device may represent a valuable tool to improve treatment modalities in patients treated with antiplatelet medication and conditions requiring urgent neurosurgical therapy.     

抗凝及抗血小板药物治疗与颅内出血的关系分析

目的　探讨口服抗凝及抗血小板药物治疗有关颅内出血的危险因素 ,分析与此相关的临床和放射学资料。方法　所有病例分为 3组 ,1组为与抗凝及抗血小板有关的颅内出血病人 ,对病人CT表现、临床症状、血小板、凝血因子筛选试验 ,出血部位和体积 ,住院 3 0d死亡率进行分析。 2组随机选取同期住院的自发性脑出血病人 ,方法同上。 3组为长期口服抗凝及抗血小板药物而无颅内出血者。结果　 1组与 2组比较 ,前者有卒中史者比较高 ,出血体积大 ,临床表现重 ,预后差。 1组与 3组相比较 ,抗凝及抗血小板治疗时间短 ,血小板数减少 ,凝血酶原时间、凝血酶时间延长。结论　抗凝及抗血小板治疗有关的颅内出血比自发性颅内出血体积大 ,死亡率高 ,抗凝及抗血小板药物过量是主要危险因素。对抗凝及抗血小板治疗病人应定期进行止血功能检测 ,尤其在第1年 ,有助于减少颅内出血的发生