Anticoagulation for the Acute Management of Ischemic Stroke

Few prospective studies support the use of anticoagulation during the acute phase of ischemic stroke, though observational data suggest a role in certain populations. Depending on the mechanism of stroke, systemic anticoagulation may prevent recurrent cerebral infarction, but concomitantly carries a risk of hemorrhagic transformation. In this article, we describe a case where anticoagulation shows promise for ischemic stroke and review the evidence that has discredited its use in some circumstances while showing its potential in others.     

DIURNAL VARIATION OF HAEMOSTATIC RESPONSE TO EXERCISE IN YOUNG SEDENTARY MALES

The aim of this study was to evaluate diurnal variations in the haemostatic response to submaximal exercise performed by young, sedentary men. Fifteen healthy young sedentary males aged 25.6 ± 1.34 (mean ± SD) years performed two exercise sessions, morning and evening, at 70% of maximal oxygen consumption (V.O₂max) on a cycle ergometer for 30 min. Platelet count (PC), activated partial thromboplastin time (aPTT), prothrombin time (PT), fibrinogen, tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) activity were measured as dependent variables. Exercise produced significant increases in PC and fibrinogen for both sessions (P ≤ 0.05), which returned to the resting values after recovery only in the evening session. APTT and PT shortened immediately after exercise, which remained after recovery for both sessions (P ≤ 0.01). Exercise presented significant increases in tPA activity (P ≤ 0.001), which returned to the baseline after recovery in both exercises. PAI-1 activity was significantly higher during the morning than evening (P ≤ 0.05), but no longer demonstrated exercise-related changes. It was found that exercise caused activation of both coagulation and fibrinolysis processes, partly related to the time of the day when the exercise was performed.     

Incidence and predictors of left atrial thrombus in patients with atrial fibrillation prior to ablation in the real world of China

BackgroundThe present study was to evaluate the value of CHADS2 and CHA2DS2VASC scores on predicting left atrial (LA) or left atrial appendage (LAA) thrombus in atrial fibrillation (AF) patients prior to ablation in the real world of China.Methods and resultsA total of 397 patients with non-valvular AF were analyzed to determine the relationship between CHADS2 and CHA2DS2VASC scores and LA/LAA thrombus identified on transesophageal echocardiography prior to radiofrequency ablation(RFA). LA/LAA thrombus was present in 38 patients (9.6%). There was a strong association between higher CHADS2 score or CHA2DS2VASC score and LA/LAA thrombus. No thrombus was identified in patients with CHA2DS2VASC score of 0 regardless of anticoagulation status. However, LA/LAA thrombus was detected in 2.9% patients with CHADS2 score of 0 without adequate anticoagulation, while no thrombus was present in the patients with CHADS2 score of 0 with adequate anticoagulation. Univariate analysis showed that heart failure (LVEF＜50%), LA≥40 mm, diabetes mellitus, previous stroke or TIA, CAD, hypertension, inadequate anticoagulation therapy, CHADS2 score of ≥2 and CHA2DS2VASC score of ≥2 were significantly associated with LA/LAA thrombus. Multivariable Cox regression analysis demonstrated that CHA2DS2VASC score of ≥2 (p = 0.02) and previous stroke or TIA (p = 0.04) were independently associated with LA/LAA thrombus regardless of anticoagulation status. ROC curve analysis showed that higher CHADS2 score and CHA2DS2VASC score could be similarly used to predict the presence of LA thrombus.ConclusionsBoth higher CHA2DS2VASC and CHADS2 scores were associated with LA/LAA thrombus in non-valvular AF patients prior to ablation. Although CHA2DS2VASC score and CHADS2 score had similar value to predict LA/LAA thrombus, CHA2DS2VASc score was better to identify low-risk patients for LA/LAA thrombus than CHADS2 score without anticoagulation. There will be a possibility of performing AF ablation or cardioversion in patients with a CHA2DS2VASC of 0 without TEE or anticoagulation therapy. The safety need to be verified by more multicentre randomized controlled clinical trails.     

实时影像融合的超声虚拟导航技术联合射频消融术治疗原发性肝癌合并门静脉癌栓患者的疗效及对血清Bax、Cyfra21-1的影响

摘要 目的：探讨实时影像融合的超声虚拟导航技术联合射频消融术治疗原发性肝癌合并门静脉癌栓患者的疗效及对血清BCL-2同源的水溶性相关蛋白（Bax）、细胞角蛋白19片段（Cyfra21-1）的影响。方法：选择本院2017年1月到2021年4月收治的原发性肝癌合并门静脉癌栓患者82例作为研究对象,根据1：1随机数字表法将患者分为虚拟导航组与对照组各41例,虚拟导航组给予实时影像融合的超声虚拟导航技术联合射频消融术治疗,对照组给予单纯超声引导联合射频消融术治疗。结果：虚拟导航组的进针次数、融合时间、布针时间少于对照组（P<0.05）;虚拟导航组治疗后3个月的胆汁瘤、肝脓肿、膈肌损伤、肺部感染等并发症发生率为4.9 %,低于对照组的29.3 %（P<0.05）。虚拟导航组治疗后3个月的总有效率为82.9 %,高于对照组的51.2 %（P<0.05）。两组治疗后3个月的血清谷丙转氨酶（ALT）、谷草转氨酶（AST）水平低于治疗前,虚拟导航组低于对照组（P<0.05）。两组治疗后的血清Bax、Cyfra21-1含量低于治疗前,虚拟导航组低于对照组（P<0.05）。结论：实时影像融合的超声虚拟导航技术联合射频消融术治疗原发性肝癌合并门静脉癌栓能降低血清Bax、Cyfra21-1含量,改善患者的肝功能,提高消融效率,还可减少并发症的发生,最终提高患者的总体治疗效果。     

Simulation of blood flow in a small-diameter vascular graft model with a swirl (spiral) flow guider

Small-diameter vascular grafts are in large demand for coronary and peripheral bypass procedures, but present products still fail in long-term clinical application. In the present communication, a new type of small-diameter graft with a swirl flow guider was proposed to improve graft patency rate. Flow pattern in the graft was simulated numerically and compared with that in a conventional graft. The numerical results revealed that the swirl flow guider could indeed make the blood flow rotate in the new graft. The swirling flow distal to the flow guider significantly altered the flow pattern in the new graft and the ve- locity profiles were re-distributed. Due to the swirling flow, the blood velocity near the vessel wall and wall shear rate were greatly enhanced. We believe that the increased blood velocity near the wall and the wall shear rate can impede the occurrence of acute thrombus formation and intimal hyperplasia, hence can improve the graft patency rate for long-term clinical use.     

A novel naphthalimide derivative reduces platelet activation and thrombus formation via suppressing GPVI

Naphthalimide derivatives have multiple biological activities, including antitumour and anti-inflammatory activities. We previously synthesized several naphthalimide derivatives; of them, compound 5 was found to exert the strongest inhibitory effect on human DNA topoisomerase II activity. However, the effects of naphthalimide derivatives on platelet activation have not yet been investigated. Therefore, the mechanism underlying the antiplatelet activity of compound 5 was determined in this study. The data revealed that compound 5 (5–10 μM) inhibited collagen- and convulxin- but not thrombin- or U46619-mediated platelet aggregation, suggesting that compound 5 is more sensitive to the inhibition of glycoprotein VI (GPVI) signalling. Indeed, compound 5 could inhibit the phosphorylation of signalling molecules downstream of GPVI, followed by the inhibition of calcium mobilization, granule release and GPIIb/IIIa activation. Moreover, compound 5 prevented pulmonary embolism and prolonged the occlusion time, but tended to prolong the bleeding time, indicating that it can prevent thrombus formation but may increase bleeding risk. This study is the first to demonstrate that the naphthalimide derivative compound 5 exerts antiplatelet and antithrombotic effects. Future studies should modify compound 5 to synthesize more potent and efficient antiplatelet agents while minimizing bleeding risk, which may offer a therapeutic potential for cardiovascular diseases.     

内皮细胞-血小板血栓体外模型的建立及分析

在内皮细胞培养技术、荧光显微技术和计算机图象处理技术的基础上,建立了内皮细胞－血小板血栓体外动力学模型及其计算机定量分析系统。通过锥板血流模拟装置（Ｃｏｎｅ－ＰｌａｔｅＳｙｓｔｅｍ）结合光－色素法在体外产生血小板血栓,并利用计算机图像处理技术,研究分析了不同剪切应力作用下,内皮细胞的形态变化及血小板吸附情况,定量分析血小板和内皮细胞之间相互作用。该实验模型及其定量分析系统的建立,为深入研究血栓形成和动脉粥样硬化提供了一套在细胞及分子层次作用机理的研究方法,并可进行微量、快速、动态的抗血栓药物的筛选     

Rheological study on coagulation of blood with special reference to the triggering mechanism of venous thrombus formation

A markedly reduced blood flow, an elevation of hematocrit and an increased aggregability of erythrocytes [red blood cells (RBCs)] are risk factors for venous thrombus formation (intravascular blood coagulation). However, these risk factors alone seem to be insufficient to stimulate the coagulation cascade in the absence of a primary triggering mechanism. In this paper, our rheological and biochemical studies on blood coagulation, especially focusing on procoagulant activity of RBCs, are summarized. It is shown that the intrinsic coagulation pathway is triggered by the activation of factor IX (F-IX) by RBCs. The F-IX-activating enzyme in normal human erythrocyte (RBC) membranes was purified, identified and characterized. The activation of F-IX by RBCs was enhanced by a decrease in flow shear rate and an elevation in hematocrit. The procoagulant ability of RBCs and coagulation of blood obtained from individuals with a relatively high level of hypercoagulability were enhanced compared with those for normals. The studies demonstrated a new triggering mechanism for coagulation or thrombus formation that may occur under stagnant flow conditions.     

Thrombus Aspiration during Percutaneous coronary intervention in Acute non-ST-elevation myocardial infarction Study (TAPAS II)-Study design

Background and Objective. The Thrombus Aspiration during Percutaneous coronary intervention in Acute myocardial infarction Study (TAPAS) has shown that thrombus aspiration improves myocardial perfusion and clinical outcome compared with conventional primary percutaneous coronary intervention (PCI) in patients with ST-segment-elevation myocardial infarction. Impaired myocardial perfusion due to spontaneous or angioplasty-induced embolisation of atherothrombotic material also occurs in patients with non-ST-elevation myocardial infarction (NSTEMI). The aim of this study is to determine whether thrombus aspiration before stent implantation will result in improved myocardial perfusion in patients with NSTEMI compared with conventional PCI. Study design. The study is a single-centre, prospective, randomised trial with blinded evaluation of endpoints. The planned inclusion is 540 patients with acute NSTEMI who are candidates for urgent PCI. Patients are randomised to treatment with manual thrombus aspiration or to conventional PCI. The primary endpoint is the incidence of myocardial blush grade 3 after PCI. Secondary endpoints are coronary angiographic, histopathological, enzymatic, electrocardiographic and clinical outcomes including major adverse events at 30 days and one year. Implications. If thrombus aspiration leads to significant improvement of myocardial perfusion in patients with acute NSTEMI it may become part of the standard interventional approach. (Neth Heart J 2009;17:409–13.)     

Variations of dissection properties and mass fractions with thrombus age in human abdominal aortic aneurysms

Introduction

Thrombus ages, defined as four relative age phases, are related to different compositions of the intraluminal thrombus (ILT) in the abdominal aortic aneurysm (AAA) (Tong et al., 2011b). Experimental studies indicate a correlation between the relative thrombus age and the strength of the thrombus-covered wall.

Methods

On 32 AAA samples we performed peeling tests with the aim to dissect the material (i) through the ILT thickness, (ii) within the individual ILT layers and (iii) within the aneurysm wall underneath the thrombus by using two extension rates (1 mm/min, 1 mm/s). Histological investigations and mass fraction analysis were performed to characterize the dissected morphology, to determine the relative thrombus age, and to quantify dry weight percentages of elastin and collagen in the AAA wall.

Results

A remarkably lower dissection energy was needed to dissect within the individual ILT layers and through the thicknesses of old thrombi. With increasing ILT age the dissection energy of the underlying intima–media composite continuously decreased and the anisotropic dissection properties for that composite vanished. The quantified dissection properties were rate dependent for both tissue types (ILT and wall). Histology showed that single fibrin fibers or smaller protein clots within the ILT generate smooth dissected surfaces during the peeling. There was a notable decrease in mass fraction of elastin within the thrombus-covered intima–media composite with ILT age, whereas no significant change was found for that of collagen.

Conclusions

These findings suggest that intraluminal thrombus aging leads to a higher propensity of dissection for the ILT and the intima–media composite of the aneurysmal wall.