Successes, failures and complications in thrombolytic therapy in peripheral, arterial and venous occlusions]

Thrombocytic therapy in peripheral arterial and venous vessel occlusion represents a clearly described alternative towards the surgery of vessels. A success rate of 36.5% can be found in subacute peripheral arterial thrombosis and 46.3% in subacute thrombotic occlusion of a bypass-graft. Contrary to that, a rate of 29.8% can be found in complications or side-effects respectively. In cases of peripheral deep venous thrombosis, a partial or full success can be found in 72%. However, the rate of complication amounting to 44.2% is comparatively high. The longer thrombolytic therapy with streptokinase or urokinase will last, the more frequently and more serious will be the complications, such as bleedings of different kind as well as increase of temperature to mention the most frequent ones. The application of urokinase is absolutely possible today, however, the use of urokinase seems to be only justified, if a thrombolytic therapy with streptokinase was carried out successfully and a subsequent surgical therapy was not possible. The present costs of this preparation are far too high for urokinase to be applied routinely. A thrombolytic therapy with SK as well as with UK has to be followed by an anticoagulant treatment.     

Debate: Should the elderly receive thrombolytic therapy, or primary angioplasty, for acute myocardial infarction? The case for primary angioplasty

As the population ages the number of elderly patients presenting with acute myocardial infarction (AMI) will continue to increase. There has been no head-to-head trial of thrombolytic therapy versus primary percutaneous coronary intervention (PCI) in this patient cohort, but there is evidence that favors primary PCI. Most elderly patients are candidates for primary PCI, but many have contraindications to thrombolytic therapy. Hemorrhagic complications are more common in the elderly, and many of these patients present with conditions in which thrombolytic agents have decreased efficacy, such as heart failure or prior bypass surgery. PCI can also obviate the need for further risk stratification in most patients.     

Thrombolysis after acute myocardial infarction: Are Canadian physicians up to the challenge?

Acute myocardial infarction (AMI) evolves as a time-dependent wave front of ischemia when the abrupt rupture of an unstable fatty plaque initiates coronary thrombosis. The prospect of salvaging potentially viable myocardial tissue has led to the development of reperfusion strategies using thrombolytic agents. The efficacy of thrombolytic therapy is determined in large measure by the speed with which it is initiated. It is therefore vital to minimize the "door-to-needle" time once a patient with AMI arrives at the emergency department. In this issue (see pages 497 to 505) Dr. Jafna L. Cox and associates report that Canadian centres participating in the GUSTO-I trial were significantly slower to initiate thrombolytic therapy than their US counterparts. In this editorial Cox and associates'' report is reviewed against the background of similar trials, and strategies to minimize delays in the initiation of thrombolytic therapy are suggested.     

Debate: Should the elderly receive thrombolytic therapy or primary angioplasty?

Thrombolysis and primary angioplasty are both recommended reperfusion strategies for elderly patients presenting with myocardial infarction (MI). Primary angioplasty is most beneficial in high-risk patients. While the elderly have a high absolute risk of dying or developing complications after MI, they also have an increased risk of intracranial haemorrhage if they are given thrombolytic therapy. It could therefore be reasonably argued that primary angioplasty is the reperfusion strategy of choice in the elderly. However, primary angioplasty has not been shown to have a greater relative benefit than thrombolytic therapy in the elderly. Recent data from the Fibrinolytic Therapy Trialists' (FTT) Collaborative Group show that thrombolytic therapy significantly reduces mortality compared with control treatment in patients over 75 years of age presenting within 12 h of symptom onset, with ST-segment elevation or bundle branch block. Future advances in adjunctive therapies may improve myocyte perfusion and hence the outcomes achieved by both invasive and noninvasive reperfusion strategies. Better thrombolytic regimens incorporating adjunctive agents such as bivalirudin may reduce the risk of intracranial haemorrhage. Few hospitals can provide a 24-h primary angioplasty service with door-to-balloon times consistently less than 90 min, and thrombolytic therapy is therefore a far more practical option in most instances.     

Recommendations for ensuring early thrombolytic therapy for acute myocardial infarction. The Heart and Stroke Foundation of Canada,the Canadian Cardiovascular Society and the Canadian Association of Emergency Physicians for the Emergency Cardiac Care Coalition.

OBJECTIVE: To recommend practical steps to ensure early thrombolytic therapy and thereby reduce mortality and morbidity associated with acute myocardial infarction (AMI). OPTIONS: Various factors were considered that influence time to thrombolysis related to patients, independent practitioners and health care systems. OUTCOMES: Reduction in morbidity and mortality associated with AMI. EVIDENCE: Early initiation of thrombolytic therapy reduces morbidity and mortality associated with AMI. The ECC Coalition analysed the factors that might impede early implementation of thrombolytic therapy. VALUES: Published data were reviewed, and recommendations were based on consensus opinion of the Emergency Cardiac Care (ECC) Coalition. The ECC Coalition comprises 20 professional, nongovernment and government organizations and has a mandate to improve emergency cardiac care services through collaboration. BENEFITS, HARMS AND COSTS: Early thrombolytic therapy reduces morbidity and mortality associated with AMI. Implementation of the recommendations will result in reduced time to thrombolytic therapy, streamlining of current practices and enhanced cooperation among health care professionals to expedite care. Depending on existing practices, implementation may require protocol development, and public and professional education. Although costs are associated with educating the public and health care professionals, they are outweighed by the financial and social benefits of reduced morbidity and mortality. RECOMMENDATIONS: Early recognition of AMI symptoms by the public and health care professionals, early access to the emergency medical services system and early action by emergency care providers in administering thrombolytic therapy (within 30 minutes after the patient''s arrival at the emergency department). VALIDATION: No similar consensus statements or practice guidelines for thrombolytic therapy in Canada are available for comparison.     

Plasminogen activators: general aspects and recent developments

Considerable interest in plasminogen activators as human thrombolytic drugs has stimulated rapid biotechnologic progresses. These enzymes have been classified in two immunochemically distinct groups: "urokinase-like" activators or u-PA which do not interact with fibrin and "tissue activator-like" activators or t-PA which interact with fibrin. Plasminogen activators are widely distributed in normal and malignant tissues and they are implicated in various physiological and pathological processes. They maintain the functional integrity of the vascular system and their presence may be of importance in tissue remodeling and cell migration. Urokinase and streptokinase are used in human thrombolytic therapy. However, the properties displayed by t-PA suggest that this enzyme may be a superior fibrinolytic agent. The primary structures of urokinase and t-PA are known; both enzymes have been synthesized by DNA technology. In order to produce t-PA in large quantities by gene cloning, intensive studies are conducted by pharmaceutical industries. Clinical trials using t-PA for dissolving thrombi in coronary heart disease, strokes and pulmonary embolism are in progress. This review presents the molecular and structural properties of plasminogen activators, as well as related physiological, pathological and therapeutic aspects.     

Use of urokinase in acute myocardial infarction

In a prospective study 88 patients with acute MI were treated with urokinase. In comparison to a control group without thrombolytic therapy 50% of the urokinase treated patients showed an improvement as well of coronary sinus blood flow as of parameters of QRST mapping.     

The potential improvement of thrombolytic therapy by targeting with bispecific monoclonal antibodies: Why they are used and how they are made

The generation of the proteolytic enzyme plasmin from its inactive precursor plasminogen, mediated by so called plasminogen activators, is the essential step in thrombolytic therapy. Plasmin is responsible for the degradation of the insoluble fibrin, the major component of a thrombus, to soluble fibrin degradation products. So far, the use of the more recently developed thrombolytic agents single-chain urokinase-type plasminogen activator (scu-PA) and tissue-type plasminogen activator (t-PA) were disappointing, mainly due to some of their negative propertiesin vivo, i.e., rapid inhibition and/or hepatic clearance. Besides some background information on the haemostatic balance; t-PA and scu-PA structure; and mechanisms of action, we here review some reported attempts to improve on these agents for thrombolytic therapy following various strategies. One of the more potential strategies, antibody-targeted thrombolytic therapy using bispecific monoclonal antibodies, is discussed somewhat more extensively, as are the several procedures that can befollowed for bispecific antibody preparation.     

Flow-induced permeation of non-occlusive blood clots: an MRI study and modelling

The success of clot thrombolysis very much depends on efficient clot permeation with blood plasma carrying the thrombolytic agent. In this paper clot permeation was studied by dynamic magnetic resonance imaging (MRI) on artificial non-occlusive blood clots inserted in an artificial circulation system filled with blood plasma to which an MRI contrast agent was added. The MRI results revealed that clot permeation is much faster and more efficient at the entrance of the flow channel across the clot. Clot permeation with fluid was simulated numerically as well. The simulation was based on numerical solution of Navier-Stokes equations for the flow in the channel and within the clot. The clot was considered as a porous material with known permeability and porosity. Based on the calculated velocity profiles, concentration profiles of fluid in the clot were modelled. These agreed well with the MRI results. The presented model of clot permeation with fluid may also serve as a useful extension to numerical modelling of dissolution of non-occlusive blood clots during thrombolytic therapy.     

静脉溶栓时机对急性ST段抬高型心肌梗死患者溶栓效果及主要不良心脏事件发生率的影响

目的:探讨静脉溶栓时机对急性ST段抬高型心肌梗死患者溶栓效果及主要不良心脏事件发生率的影响。方法:将2016年1月至2017年12月我院接诊的314例急性ST段抬高型心肌梗死患者纳入本研究,按照溶栓治疗时间不同分为A组(发病至溶栓时间6 h)172例、B组(发病至溶栓时间为6～12 h)102例和C组(发病至溶栓时间12 h)40例,比较三组患者溶栓效果、溶栓后ST段回落情况以及住院期间主要不良心脏事件发生情况。结果:A组患者梗死冠脉溶通率、溶栓后ST段回落幅度高于B组和C组,且B组高于C组,差异均有统计学意义(P0.05)。A组患者治疗后ST段回落最大幅度所需时间、住院期间主要不良心脏事件总发生率低于B组和C组,且B组低于C组,差异均有统计学意义(P0.05)。结论:急性ST段抬高型心肌梗死患者发病后6 h内静脉溶栓治疗梗死冠脉溶通率更高、ST段回落效果更好,可降低住院期间主要不良心脏事件发生风险。     

A specific marker of thrombolysis: DDE complex

A specific determination of fibrin degradation product (FbDP) is essential for the monitoring of thrombolytic therapy. In patients under thrombolytic therapy, even with tpA (tissue type plasminogen activator) fibrinogen is degraded, and fragment D derived from fibrinogen degradation, is evidenced in the plasma of treated patients. In order to determine specifically the FbDP, even in the presence of fragment D, we take into account the fact that FbDP are complexes such as DDE complex. Therefore a new Elisa technique is proposed. FbDP and fragment D are captured from plasma by immobilized anti D neo monoclonal antibody which recognizes an epitope accessible on fragment D but does not react with undegraded fibrinogen. DDE complexes are then detected specifically using a peroxidase-labelled anti E antibody. The advantage of this technique is discussed in this paper.     

老年颈内动脉系统急性脑梗死动脉溶栓的疗效观察

目的:探讨老年颈内动脉系统急性脑梗死动脉溶栓的疗效。方法:对我院老年科收治的63例老年颈内动脉系统急性脑梗死随机分为股动脉组以及颈动脉组,其中股动脉组患者30例,对其采用经皮股动脉穿刺微导管介入尿激酶溶栓治疗,颈动脉组患者33例,对其采用经皮患侧颈动脉穿刺尿激酶溶栓治疗。结果:对两组患者治疗前、术后2h以及术后30d采用NIHSS评分比较,两组患者NIHSS评分在术后2h及术后30d均较术前有明显改善(P<0.05);对两组患者治疗相关情况比较,股动脉组患者术后2h血管再通率明显高于颈动脉组(P<0.05),两组颅内出血率未显示出统计学差异性;对两组患者术后30d牛津残障OHS评分、BI指数比较,股动脉组患者明显优于颈动脉组(P<0.05)。结论:对老年急性脑梗死患者采用经皮股动脉穿刺微导管介入或采用经皮患侧颈动脉穿刺尿激酶溶栓治疗,均可有效改善患者预后,提高患者的临床疗效,两组相比较,股动脉组更能显示出优良的治疗率。     

Position and developmental trends in fibrinolytic therapy

Increasing insight into the mechanism of fibrinolysis and particularly into the formation and release of plasminogen activator has led to more effective thrombolytic therapy. The understanding of the mechanism of thrombolysis has provided the possibility to improve the therapeutic effects of the fibrinolytic agents streptokinase and urokinase. Further advances in thrombolytic therapy are expected by the use of the plasminogen activator from tissue endothelium and pro-urokinase. Acylation of fibrinolytic enzymes will lead to beneficial effects (depot effect, protection from intrinsic inhibitors). Due to the extensive research into substances with fibrinolytic and thrombolytic effects a new generation of activators of fibrinolysis is expected that interfere with the biosynthesis and release of plasminogen activator of the vessel wall and that are suited for treatment of hypofibrinolytic states.     

Knowledge of Thrombolytic Therapy for Acute Ischemic Stroke among Community Residents in Western Urban China

Background and Purpose

Thrombolytic therapy rate for acute ischemic stroke remains low, and improving public awareness of thrombolytic therapy may be helpful to reduce delay and increase chances of thrombolytic therapy. Our purpose was to survey the level of knowledge about thrombolytic therapy for acute ischemic stroke among community residents in Yuzhong district, Chongqing, China.

Methods

In 2011, a population-based face-to-face interview survey was conducted in Yuzhong district, Chongqing. A total of 1500 potential participants aged ≥18 years old were selected using a multi-stage sampling method.

Results

A total of 1101 participants completed the survey. Only 23.3% (95% CI = 20.8 to 25.8) were aware of thrombolytic therapy for acute ischemic stroke, of whom 59.9% (95% CI = 53.9 to 65.9) knew the time window. Awareness of thrombolytic therapy was higher among young people, those with higher levels of education and household income, those with health insurance, and those who knew all 5 stroke warning signs, while awareness of the time window was higher among those aged 75 years or older. Multivariate logistic regression analysis showed that awareness of thrombolytic therapy was independently associated with age, education level, health insurance and knowledge of stroke warning signs (P<0.05).

Conclusions

In this population-based survey the community residents have poor awareness of thrombolytic therapy for acute ischemic stroke.     

Microbial fibrinolytic enzymes: an overview of source, production, properties, and thrombolytic activity in vivo

Accumulation of fibrin in the blood vessels usually results in thrombosis, leading to myocardial infarction and other cardiovascular diseases. For thrombolytic therapy, microbial fibrinolytic enzymes have now attracted much more attention than typical thrombolytic agents because of the expensive prices and the undesirable side effects of the latter. The fibrinolytic enzymes were successively discovered from different microorganisms, the most important among which is the genus Bacillus from traditional fermented foods. The physiochemical properties of these enzymes have been characterized, and their effectiveness in thrombolysis in vivo has been further identified. Therefore, microbial fibrinolytic enzymes, especially those from food-grade microorganisms, have the potential to be developed as functional food additives and drugs to prevent or cure thrombosis and other related diseases.Dr. Yong Peng was invited by the editor-in-chief, Professor Dr. A. Steinbüchel, to write this review     

尿激酶静脉溶栓治疗急性心肌梗死的疗效观察--附35例报告

目的 观察尿激酶静脉溶栓治疗急性心肌梗死的疗效.方法将66例急性心肌梗塞住院患者随机分成两组,溶栓组35例在常规治疗的同时,用尿激酶静脉溶栓治疗,非溶栓组仅用常规治疗,两组进行比较分析.结果 溶栓组血管再通率74.3%,非溶栓组为25.81%,两组间有明显差异(P<0.05),住院4周的病死率,溶栓组为2.86%,非溶栓组为16.16%,两组间有显著差异(P<0.01).结论 尿激酶静脉溶栓能明显提高急性心肌梗死患者的血管再通率和抢救成功率,降低近期病死率.     

Mechanism of fibrinolysis and thrombolytic therapy

The thrombolytic treatment with plasminogen activators, such as physiological tissue-type plasminogen activator (t-PA), suffers from a number of significant limitations. There is a resistance to reperfusion and acute coronary reocclusion. The peculiarity of t-PA and one-chain urokinase treatment is their using in very high doses. Thus the process of thrombolytic therapy is proceeding with a deviation from the fibrinolytic mechanism, which is needs of a little quantity of tissue-type plasminogen activator and provides the physiologic thrombolysis without systemic complication. The estimation of this disaccordance suggests, the possible reasons of these complications.     

超敏C 反应蛋白与深静脉血栓形成的相关性分析

目的：分析超敏C反应蛋白（hs-CRP）与深静脉血栓形成（DVT）的相关性,探讨炎症反应在DVT 发生及发展中的作用。方 法：选取2013 年9 月至2015 年3 月我院收治的DVT 患者113 例,按病变部位分为中央型、周围型以及混合型,按发病时间分为 急性期、亚急性期以及慢性期。另选取同期体检的健康志愿者50例作为对照组。检测所有研究对象血清hs-CRP水平。结果：DVT 患者血浆hs-CRP 高于正常健康人群（P＜0.05）;不同临床分型DVT 患者血浆hs-CRP 水平不同,混合型最高,周围型最低,差异 具有统计学意义（P＜0.05）;不同发病时期DVT 患者血浆hs-CRP 水平不同,急性期最高,恢复期最低,差异具有统计学意义（P＜ 0.05）;接受溶栓治疗的DVT 患者术后3 天血浆hs-CRP 水平持续升高,术后第5 天开始快速下降。结论：hs-CRP 可作为DVT 诊 断的参考指标,DVT发生及发展与炎症反应存在相关性。     

食品纤溶酶研究概况

溶栓疗法是血栓性疾病安全有效的治疗手段,开发安全高效、廉价的新型纤溶酶对于预防与治疗血栓性疾病具有重要意义。近年来,在许多亚洲传统发酵食品中如日本纳豆、韩国大豆酱、中国豆豉、发酵虾酱等中均发现有丰富的纤溶酶资源。本文重点介绍传统发酵食品中纤溶酶的研究概况及其开发前景。