抗凝药在缺血性卒中防治中的地位

抗凝是预防和治疗缺血性卒中的重要手段之一,但在降低卒中复发风险的同时有可能增加出血事件.文章通过回顾抗凝药在缺血性卒中防治中的应用以及新型抗凝药的研究,评价了抗凝药在缺血性卒中防治中的地位.     

缺血性卒中患者出血性转化的治疗

10%~15%的缺血性卒中患者可出现出血性转化,其治疗较为复杂,主要包括血压管理、纠正凝血障碍和治疗并发症(包括颅内压升高).目前的研究主要是寻找抗凝和溶栓治疗后出血性转化的治疗方案,旨在改善卒中患者的预后.     

利伐沙班临床应用中国专家建议——非瓣膜病心房颤动卒中预防分册

心房颤动(房颤)最常见的心律失常之一.调查数据显示,我国30 ～ 85岁居民中房颤患病率为0.77％[1].血栓栓塞并发症是房颤致死致残的主要原因,而卒中是最常见的表现类型.房颤是卒中的独立危险因素,罹患房颤可使卒中风险增加5倍[2].而房颤所致的卒中致死率、致残率及复发率很高[3],给患者及社会带来严重经济负担.大量临床研究证实,抗凝治疗在房颤卒中预防中占有重要地位,合理应用抗凝药物可显著降低缺血性卒中发生率,并得到国内外众多权威指南的广泛推荐[4-6].然而目前我国房颤患者抗凝治疗显著不足[1],传统抗凝药物华法林需定期监测凝血相关指标和调整剂量,且与多种药物和(或)食物存在相互作用,限制了其临床广泛应用.     

抗栓治疗药物进展

在正常情况下,血液促凝和抗凝机制处于一个动态平衡状态。在多种危险因素,如血管壁损伤、血液成分变化、血流速度及状态变化等的作用下,机体的凝血与抗凝平衡失调,凝血作用占优势,血液循环中的有形成分形成栓子,造成管腔部分或完全栓塞,从而造成严重后果,如急性心肌梗死、缺血性卒中、肺栓塞、心房血栓形成、弥散性血管内凝血。近年来,     

非瓣膜性心房颤动患者卒中预防中的抗凝治疗

非瓣膜性心房颤动患者是缺血性卒中的高危人群,临床上主要采用抗凝治疗预防其卒中的发生.然而,常规口服抗凝药华法林因某些限制存在一定的困难.一些新型口服抗凝药,如直接凝血酶抑制药、凝血因子Xa抑制药在非瓣膜性心房颤动患者的卒中预防中显示了其前途.     

缺血性卒中治疗与预防的研究进展

在世界范围内,卒中领域的研究无疑以缺血性卒中为主,而相关研究涉及面非常广泛,如溶栓时间、抗凝治疗、非药物支架置入等.本文对新发表的缺血性卒中急性期治疗和预防方面的研究进展进行综述.     

缺血性卒中与凝血病的实验诊断

高凝状态是缺血性卒中的少见病因之一。文章总结了缺血性卒中患者出现凝血病的概率,分析了凝血试验结果的影响因素及相关因素,对现有的凝血病诊断性试验作出了评价,指出应结合缺血性卒中患者的病史和临床特征,有针对性地选择试验时机与特异性凝血试验方法。     

缺血性卒中与凝血病的实验诊断

高凝状态是缺血性卒中的少见病因之一。文章总结了缺血性卒中患者出现凝血病的概率，分析了凝血试验结果的影响因素及相关因素，对现有的凝血病诊断性试验作出了评价，指出应结合缺血性卒中患者的病史和临床特征，有针对性地选择试验时机与特异性凝血试验方法。     

心房颤动与缺血性卒中的预防

心房颤动(AF)作为缺血性卒中的重要危险因素已经得到确认.但在卒中预防实践中,如何正确选择AF患者进行抗凝治疗,哪些AF患者适用抗凝治疗,哪种抗凝强度更加合理,以及如何权衡长期抗凝治疗的风险和效益,均存在一定的争论.文章对此进行了分析.     

卒中的抗栓治疗

预防卒中复发:卒中患者在应用肝素的过程中,始终存在风险和效益的平衡,例如对急性缺血性卒中抗凝治疗的荟萃分析显示,虽然抗凝治疗可降低卒中复发,但出血事件显著增加。所以ASA2003抗凝指南建议,对于急性缺血性卒中患者不推荐常规抗凝改善神经预后和预防卒中复发。但迄今为止,惟一一项在亚裔人中进行的研究———FISS研究显示了不同的结果,对306例急性缺血性卒中患者的研究显示,那屈肝素0·4ml,2次/d,是安全有效的,每5例患者中可以避免1例患者的死亡或生活依赖。该结果体现了亚裔人和欧美人的差异,东方人颅内狭窄相对较多,因此东西方抗凝…     

Deficiency of natural anticoagulant proteins C,S, and antithrombin in portal vein thrombosis: a secondary phenomenon?

BACKGROUND: Hereditary deficiencies of natural anticoagulant proteins are implicated in the pathogenesis of portal vein thrombosis (PVT). Secondary deficiencies of these proteins have also been reported in PVT, making interpretation of concentrations difficult. AIMS: To characterise the coagulation profiles in adult patients with PVT and to investigate the possible mechanisms of natural anticoagulant protein deficiency. PATIENTS: Twenty nine adult patients with portal hypertension caused by PVT, and normal biochemical liver function tests. METHODS: Routine coagulation profiles and concentrations of proteins C, S, and antithrombin were measured; where indicated, corresponding concentrations in parents were also measured. Synchronous peripheral and hepatic or splenic vein concentrations were compared in seven patients undergoing interventional procedures, as were peripheral concentrations before and after shunt surgery in three patients. RESULTS: Deficiencies of one or more of the natural anticoagulant proteins occurred in 18 patients (62%), with six patients having combined deficiency of all three proteins. There were strong correlations between prothrombin and partial thromboplastin time ratios and concentrations of natural anticoagulant proteins. Family studies in nine cases of anticoagulant protein deficiency revealed possible hereditary deficiency in only three cases, and significantly lower concentrations of anticoagulant proteins in all PVT cases compared with parents. Levels of anticoagulant proteins tended to be lower in hepatic veins but higher in splenic veins compared with peripheral vein concentrations. Peripheral concentrations decreased after shunt surgery. CONCLUSIONS: Deficiency of natural anticoagulant proteins is common in PVT and is probably a secondary phenomenon in most cases, occurring as part of a global disturbance of coagulation variables. The mechanism for this remains unclear but may result from a combination of reduced hepatic blood flow and portosystemic shunting itself.     

A Sensitive Test Demonstrating Lupus Anticoagulant and its Behavioural Patterns

The kaolin clotting time of platelet poor plasma was used as a sensitive test for detecting the lupus anticoagulant in mixtures of normal and patients' plasmas. Platelets were found to decrease the anticoagulant effect of a typical lupus inhibitor. Thus, high sensitivity in this test system was achieved by ensuring low platelet concentrations and omitting platelet lipid substitute. In 17 patients with disseminated lupus erythematosus (DLE), 12 had detectable inhibitor by this method, more than would be detected with routine coagulation tests. Mixing patterns were of four distinct types, representing three different modes of anticoagulant behaviour. The pattern (type 3) of plasma mixtures giving longer kaolin clotting times than the individual components could be reproduced in vitro by adding trace amounts of crude thrombin or platelet fragments to a more typical lupus anticoagulant-containing plasma; formation of such a mixing pattern by the plasma of a patient with DLE may therefore indicate activation of the coagulation pathway. Six patients with idopathic thrombocytopenic purpura (ITP) had no detectable inhibitor indicating that anti-platelet antibodies behave differently from the lupus anticoagulant.     

Blood coagulation and its regulation by anticoagulant pathways: genetic pathogenesis of bleeding and thrombotic diseases

Blood coagulation and its regulation by anticoagulant pathways: genetic pathogenesis Platelet-mediated primary haemostasis and blood coagulation have evolved as important defence mechanisms against bleeding. The formation of the platelet plug provides the initial occlusion of the vascular lesion. This is temporally co-ordinated with the activation of the coagulation system, which occurs in response to the rupture of endothelium and the exposure of blood to the extravascular tissue. The reactions of blood coagulation are carefully controlled by several anticoagulant mechanisms and under normal conditions they prevail over the procoagulant forces. Genetic or acquired disturbances of the natural balance between the pro- and anticoagulant systems may result in bleeding or thrombotic diseases.     

Natural anticoagulants and the liver

The regulation of blood coagulation is dependent on a complex interplay between procoagulant, anticoagulant and fibrinolytic proteins. Most of these proteins are synthesised in the liver and their levels are altered in patients with liver disease. The liver also plays an important role in the regulation of haemostasis throughout the clearance of activated clotting factors. It is therefore not surprising that the critically balanced coagulation system is dysregulated in patients with liver disease. In moderate liver failure bleeding disorders predominate, whereas in more advanced liver disease intravascular coagulation is commonly observed and contributes to the overall dysregulation of blood coagulation. In some patients, liver disease can be primarily caused by an abnormality of the coagulation system. These patients usually have a hypercoagulable state caused by a deficiency of a component of the natural anticoagulant system. These include protein C, protein S and antithrombin III. More recently, activated protein C resistance caused by a point mutation in the Factor V gene has been identified as an important risk factor for thrombosis. In these patients the abnormal Factor V is resistant to cleavage by activated protein C resulting in ongoing uncontrolled procoagulant drive. Both hepatic and portal vein thrombosis have been reported in these patients. Appropriate management of these patients should include a thorough assessment of their natural anticoagulant proteins and exclusion of activated protein C resistance as the cause of their thrombotic disorder.     

Anticoagulant thrombins

Thrombin plays both procoagulant and anticoagulant roles in the blood coagulation cascade. This dual role is influenced allosterically by the binding of Na⁺ near the primary specificity pocket of the enzyme. Recent findings demonstrate that it is possible to engineer recombinant thrombins that have practically lost anticoagulant activity but retain their anticoagulant properties. These anticoagulant thrombins bear substitutions in or around the Na⁺ binding site, provide important clues on structure–function relations, and offer a promising alternative to current anticoagulant therapies. In addition, they demonstrate the importance of Na⁺ as a coagulation factor and broaden our understanding of the function and regulation of all vitamin K–dependent clotting enzymes.     

Anticoagulant therapy for chronic cardiac diseases. Atrial fibrillation, valvular heart disease, congestive heart failure

In cardiology, anticoagulant therapy is absolutely indicated after mechanical valve replacement, but is much more often necessary as a prophylactic measure in atrial fibrillation for prevention of embolic stroke. For more than 50 years, there has been no alternative to the oral application of vitamin K antagonists (VKA), which are known to have a very narrow therapeutic window. Despite being highly effective in preventing embolic stroke, many patients are not adequately treated with VKA, and up to 45% of the time the values lie outside the therapeutic range. The reasons for this might be difficult adjustment of VKA dosage, interactions with drugs and food, the necessity of constant monitoring of the blood coagulation, and the fear of severe bleeding complications. More recently, different anticoagulants binding directly to thrombin or factor Xa have been developed, which allows anticoagulant therapy without the need for numerous coagulation checks, representing a major breakthrough in anticoagulant therapy. In this review, the new guidelines for the use of antithrombotic therapy in atrial fibrillation are presented, followed by a discussion of study results with the new thrombin inhibitors and factor Xa inhibitors for prevention of thromboembolic stroke. Moreover, principles of anticoagulant therapy in valvular heart disease and chronic heart failure are described.     

Simultaneous presence of tissue factor pathway inhibitor (TFPI) and low molecular weight heparin has a synergistic effect in different coagulation assays.

Injection of heparin releases tissue factor pathway inhibitor (TFPI) to the blood and, after heparin neutralization, it has been recently demonstrated that the released TFPI has an anticoagulant activity. Using recombinant TFPI (rTFPI) we have investigated how the simultaneous presence of TFPI and low molecular weight heparin (LMW heparin) affects different coagulation assays. Coagulation was measured using the activated partial thromboplastin time, the prothrombin time and a dilute tissue factor assay. The anticoagulant activity of partly purified plasma TFPI (pTFPI) was much higher than that of TFPI. However, this high anticoagulant activity was unstable, so in order to investigate the effect of pTFPI and LMW heparin we used an inhibitory antibody towards TFPI and looked at the effect of removing TFPI from plasma. When both rTFPI and LMW heparin was added to plasma a synergistic effect was observed in all assays. In the tissue factor dependent coagulation assays, the effect of adding rTFPI or removing pTFPI was more pronounced in the presence of heparin. TFPI plays a significant role in assays where the coagulation time is prolonged for some reason. This may be caused by dilution of tissue factor, by the presence of heparin or by a defect in the coagulation cascade such as that seen in haemophilia.     

Resistance to annexin A5 anticoagulant activity: a thrombogenic mechanism for the antiphospholipid syndrome

The phospholipid binding protein, annexin A5 (AnxA5), has potent anticoagulant properties that result from its forming 2-dimensional crystals over phospholipids, blocking the availability of the phospholipids for critical coagulation enzyme reactions. This article reviews the evidence that antiphospholipid antibodies can disrupt this anticoagulant shield and unmask thrombogenic anionic phospholipids, which may thereby contribute to thrombosis in patients with the antiphospholipid syndrome (APS). This mechanism for thrombosis in APS can be monitored with coagulation assays for resistance to anticoagulant activity of AnxA5.     

肺癌高凝状态的发生机制及治疗对策的新认识

肿瘤细胞的激活和肿瘤治疗等因素均可以使机体凝血系统激活而处于高凝状态.即使已使用有效的抗凝药物,血栓形成仍可能是癌症始发或者复发的表现.正常情况下,凝血系统被激活起保护作用.肿瘤本身和多种因素的刺激导致凝血系统被激活,这对于肿瘤转移的影响大于对肿瘤本身.大多数肿瘤患者死于癌症转移,所以抗凝治疗显得尤为重要.低分子肝素是抗凝治疗的较佳药物.目前使用低分子肝素治疗小细胞肺癌的血栓前状态取得了一定的效果.对癌症患者高凝状态的发生机制和危险因素的进一步探讨有助于指导临床治疗和对高危人群进行预防.     

Antikoagulation bei chronischen Herzerkrankungen

In cardiology, anticoagulant therapy is absolutely indicated after mechanical valve replacement, but is much more often necessary as a prophylactic measure in atrial fibrillation for prevention of embolic stroke. For more than 50?years, there has been no alternative to the oral application of vitamin?K antagonists (VKA), which are known to have a very narrow therapeutic window. Despite being highly effective in preventing embolic stroke, many patients are not adequately treated with VKA, and up to 45% of the time the values lie outside the therapeutic range. The reasons for this might be difficult adjustment of VKA dosage, interactions with drugs and food, the necessity of constant monitoring of the blood coagulation, and the fear of severe bleeding complications. More recently, different anticoagulants binding directly to thrombin or factor?Xa have been developed, which allows anticoagulant therapy without the need for numerous coagulation checks, representing a major breakthrough in anticoagulant therapy. In this review, the new guidelines for the use of antithrombotic therapy in atrial fibrillation are presented, followed by a discussion of study results with the new thrombin inhibitors and factor?Xa inhibitors for prevention of thromboembolic stroke. Moreover, principles of anticoagulant therapy in valvular heart disease and chronic heart failure are described.