血液透析病人透析器内凝血使用阿司匹林的治疗与护理

透析器内凝血是维持性血液透析病人常见的问题之一,透析器内凝血后可使透析膜的通透性下降,可直接影响透析效果。另外多次出现透析器内凝血给透析病人造成血液的大量丢失,更加重了患的贫血。凝血后透析器的丢弃也加重了患的经济负担。目的：本方法探索出一条简便易行,安全可靠的抗凝方法。方法：30例透析患,男18例,女12例,透析过程中病人的肝素量按照常规应用,平时每日口服阿司匹林一次,每次40mg。透析前一天睡前服160mg。结果：透析器内凝血的血透病人经口服阿司匹林后均收到了满意的效果,其中80％的病人服药后透析器内凝血现象完全消失,20％的病人虽然透析器内仍有少量凝血,但其程度较前有明显战轻。结论：对透析器内发生凝血的血液透析病人用阿司匹林抗凝,既简单方便,又能收到较好的临床效果。本方法可提高血液透析病人的透析质量,但必须按时按量服药。     

Tissue factor expression at the site of inflammation: a cross-talk between inflammation and the blood coagulation system

Recent studies have revealed a close association of the blood coagulation system with inflammation and immune reactions. The products of the cascade reaction of blood coagulation can work as inflammatory mediators or immune modulators, and, vice versa, some inflammatory or immune stimuli are linked to induction of blood coagulation. First, tissue factor (the blood coagulation initiator), the monocyte/macrophage tissue factor expression regulatory factors associated with inflammation and immune reactions, and the assembly of coagulation factors on leukocytes were reviewed. Second, evidence of leukocyte tissue factor expression and subsequent fibrin deposition were demonstrated at sites of infection or allergic reactions, using immunohistochemical staining. Third, the progress in the investigation of thrombin was reviewed from the viewpoint of its effects on inflammation (vascular permeability enhancement, leukocyte chemotaxis, chemical mediator release, etc.) and immune reactions (T-cell proliferation, cytokine production, etc.). The evidence presented here indicates a cross-talk between blood coagulation and inflammatory and immune reactions, suggesting that the products of the clotting reaction (e.g., thrombin) in lesions are real-time markers of inflammatory diseases.     

体外循环后全身炎性反应

全身炎性反应(SIRS)是体外循环手术后的常见并发症.体外循环中由于血液与体外循环装置中的气体界面及管道的作用,启动三个相交的血浆蛋白酶旁路的激活,这些旁路包括激肽-激肽释放酶系统、凝血-纤溶系统、补体系统,通过一系列的蛋白分解产生活化的致炎性介质,激活白细胞、内皮细胞及血小板,促使血管扩张及通透性增加.激活的细胞成分能分泌炎性介质包括细胞因子,增强这一反应过程,最终导致组织损伤及器官功能失调.     

Fibrinogen, fibrin and fibrin degradation products in relation to atherosclerosis

Many human atherosclerotic lesions, showing no evidence of fissure or ulceration, contain a large amount of fibrin which may be in the form of mural thrombus on the intact surface of the plaque, in layers within the fibrous cap, in the lipid-rich centre, or diffusely distributed throughout the plaque. Small mural thrombi are invaded by SMCs and collagen is deposited in patterns closely resembling the early proliferative gelatinous lesions. In experimental animals, thrombi are converted into lesions with all the characteristics of fibrous plaques, and in saphenous-vein bypass grafts, fibrin deposition is the main cause of wall thickening and occlusion. There seems little doubt that fibrin deposition can both initiate atherogenesis and contribute to the growth of plaques. Epidemiological studies indicate that increased levels of fibrinogen and clotting activity are associated with accelerated atherosclerosis, and although blood fibrinolytic activity has given inconsistent results, in arterial intima both fibrinolytic activity and plasminogen concentration are decreased in cardiovascular disease. Fibrin may stimulate cell proliferation by providing a scaffold along which cells migrate, and by binding fibronectin, which stimulates cell migration and adhesion. Fibrin degradation products, which are present in the intima, may stimulate mitogenesis and collagen synthesis, attract leukocytes, and alter endothelial permeability and vascular tone. In the advanced plaque fibrin may be involved in the tight binding of LDL and accumulation of lipid. Thus there is extensive evidence that enhanced blood coagulation is a risk factor not only for thrombotic occlusion, but also for atherogenesis. Enhanced blood coagulation frequently coexists with hyperlipidaemia and, together, these may have a synergistic effect on atherogenesis.     

Activation of blood coagulation in autoimmune skin disorders

The immune system and blood coagulation are simultaneously activated in several inflammatory systemic disorders, such as lupus erythematosus, rheumatoid arthritis and inflammatory bowel diseases. Proinflammatory cytokines, such as IL-6 and TNF-α, induce the expression of tissue factor, the main initiator of blood coagulation. Activated proteases of coagulation in turn act on protease-activated receptors, inducing the expression of various proinflammatory cytokines. This cross-talk between inflammation and coagulation amplifies and maintains the activation of both systems. This review focuses on three skin disorders: chronic urticaria (CU), which is considered autoimmune in approximately 50% of cases, bullous pemphigoid (BP), which is the prototype of autoimmune blistering disease, and psoriasis, which is an immune-mediated dermatitis. In CU, the activation of coagulation, which is due to the involvement of eosinophils and tissue factor pathways with the generation of thrombin, has local implications by increasing dermal vascular permeability. Preliminary data indicate that anticoagulant treatment with heparin and warfarin may be effective in reducing the symptoms of this disorder. In BP, the activation of coagulation seems to have both local and systemic implications. Locally, eosinophils and thrombin participate in bulla formation and tissue damage; systemically, the activation of coagulation may explain the increased thrombotic risk observed in these patients. In psoriasis, the activation of coagulation seems to be mainly systemic, potentially contributing to the increased cardiovascular risk associated with this disease.     

肺心病急性加重期患者血液流变学及凝血功能指标监测的临床意义

目的 探讨肺心病急性加重期患者血液流变学及凝血功能的变化.方法 选取2014年6月至2016年1月在我院治疗的51例肺心病急性加重期患者为急性加重组,在我院接受治疗的51例恢复期患者为恢复组和社会招募51例健康受试者为正常组,考察肺心病急性加重期患者血液流变学中红细胞计数、红细胞压积、全血高切黏度、全血低切黏度、血浆黏度、血沉,凝血功能中凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、纤维蛋白原(FIB)、凝血酶时间(TT)的变化.结果 肺心病急性加重期部分患者的红细胞计数偏离正常值范围,整体肺心病急性加重期患者的红细胞计数与恢复期和正常组受试者差异无统计学意义.肺心病急性加重期患者红细胞压积、全血高切黏度、全血低切黏度、血浆黏度、血沉均较恢复期和正常组受试者的值高,并且差异具有统计学意义(P<0.05).肺心病急性加重期患者的PT、APTT、FIB、TT高出正常值范围,并且与恢复期和正常组相比差异具有统计学意义(P<0.05).结论 肺心病急性加重期的患者血液黏度升高、凝血功能紊乱.因此血液黏度和凝血功能检查,可以作为肺心病急性加重期患者病情判定与评估的一种手段.     

Vascular activation in the histopathogenesis of Hodgkin's disease: Potential role of endothelial tissue factor in intravascular thrombosis and necrosis

Endothelial cell activation and alterations of intravascular coagulation were investigated in 27 cases of Hodgkin's disease (HD), in five cases of anaplastic large cell lymphoma (ALCL), and in ten reactive lymph nodes. Lymph node sections were immunostained for E-selectin, a molecule present on cytokine-activated endothelial cells; for tissue factor (TF), a cellular initiator of the coagulation cascade; for glycoprotein (gp) II/III, a platelet-specific antigen; and for fibrin. In HD, vascular activation was particularly prominent in the nodular sclerosis subtype, as indicated by a larger number of E-selectin-positive blood vessels (72 ± 49) compared with mixed cellularity (22 ± 37). High expression of E-selectin was associated with alterations of intravascular coagulation, as indicated by immunostaining of some vascular endothelial cells for TF, by a higher incidence of intravascular thrombi, and by the extensive presence of areas of fibrin exudation and necrosis. In ALCL, the levels of endothelial cell activation and intravascular coagulation were comparable to those of HD nodular sclerosis. In reactive nodes, some E-selectinpositive blood vessels were observed only in 3/10 cases; immunostaining for TF was not detected on endothelial cells; and alterations of intravascular coagulation were rarely observed.     

Action of venoms on blood coagulation: diagnosis of hemorrhagic syndromes

Venoms from Viperidae, Crotalidae, some Australian Elapidae and few Colubridae are a mixture of enzymes which impact on blood coagulation in several ways. These proteins can be classified as haemorragins which induce disorders of the capillary permeability, disintegrins and related proteins which disturb the clotting time while acting on plate adhesion, and proteases which cleave peptides. Venoms contain molecules directed against several targets of the coagulation system. The same molecule may present different activities. Components of snake venoms are used in diagnostic coagulation tests, fundamental research and as drugs against infectious agents, cancer or haematological disorders. The structural differences between proteins from snake venoms and natural coagulation factors and the target diversity of the venom components explain why it remains illusory to treat bleedings when acting just at symptom level. Conversely, antivenom, whose components are directed against the venom proteins, is the only aetiological therapy effective against snake envenomations.     

Electrogenic mechanism of secretion of coagulation factors

Changes in the permeability of the cell membranes of the vessel wall and of the nerve accompanied by a change in their electrical resistance lead to the liberation of coagulation factors into the medium. These factors may be membrane phospholipids which, when liberated into the cytoplasm, must modify its colloid state.     

Blood coagulation in falciparum malaria—a review

Falciparum malaria infection influences blood coagulation by various interacting pathobiological mechanisms, the most important being the overwhelming response of the host to sepsis resulting in a cytokine storm. In addition, the parasite infects the red cells leading to changes in the red cell phospholipid composition which supports blood coagulation. Red cells infected with Plasmodium falciparum also adhere to deeper tissue capillary endothelium leading to profound damage to endothelial cells leading to further activation. This results in widespread consumption of platelets and activation of blood coagulation which at times culminates in a clinically and pathologically detectable disseminated intravascular coagulation (DIC). Monocyte–macrophage system also gets activated in this infection compounding the hypercoagulable state. Heavy parasitaemia leading to occlusion of hepatic microcirculation leads to abnormalities in synthesis and secretion of coagulation factors and their inhibitors. Drugs used in the treatment for falciparum malaria can cause thrombocytopaenia, bone marrow suppression and haemolytic anaemia, all of which can interfere indirectly with blood coagulation. Microparticle formation from platelets, red cells and macrophages also causes widespread activation of blood coagulation, and this recently observed mechanism is the focus of intense research in many other inflammatory and neoplastic conditions where there is activation of blood coagulation system. Thus, in severe falciparum malaria, there is activation of blood coagulation system along with thrombocytopaenia, even before widespread DIC and coagulation failure occur.     

Mechanisms of blood coagulation induced by latex particles and the roles of blood cells

Latex particles with highly negative or positive charges shortened the clotting time of whole blood and platelet-rich plasma and activated platelet factor 3. Platelet-poor plasma was clotted by the particles with a highly negative charge, but not by those with a positive charge, except hydrophobic particles. Blood coagulation by positively-charged particles was attributed to platelet activation. An enhancement of blood coagulation was also observed in the presence of erythrocytes, leucocytes, their cell membranes or negatively charged phospholipids, and phosphatidylserine instead of platelets. Hydrophilic and low-charged particles suppressed blood coagulation.     

Chronic urticaria and coagulation: pathophysiological and clinical aspects

Chronic urticaria (CU) is a widespread skin disease, characterized by the recurrence of transient wheals and itch for more than 6 weeks. Besides autoimmune mechanisms, coagulation factors, in particular tissue factor and thrombin, might also participate in the disease pathophysiology. Tissue factor expressed by eosinophils can induce activation of blood coagulation generating thrombin which in turn can increase vascular permeability both directly, acting on endothelial cells, and indirectly, inducing degranulation of mast cells with release of histamine, as demonstrated in experimental models. D‐dimer, a fibrin degradation product, generated following activation of the coagulation cascade and fibrinolysis, has been found to be increased during urticaria exacerbations; moreover, it has been proposed as a biomarker of severity and resistance to H1‐antihistamines in CU patients. The possible role of coagulation in CU is also supported by case reports, case series and a small controlled study showing the efficacy of anticoagulant therapy in this disease. The purpose of this review was to summarize the available data on the possible contribution of coagulation to the pathophysiology of CU focusing on clinical aspects and possible future therapeutic developments.     

Activation of coagulation and fibrinogen loss after using an extracorporeal circulation

Alterations of the coagulation potential of heparinized blood after using an extracorporeal circulation have been studied by means of a toluidine blue-calcium chloride reagent. This technique was originally used to detect the effect of activation by contact on the coagulation mechanism in heparinized blood. It has been shown that it also detects, in the presence of heparin, the clotpotentiating effect of blood cell contents liberated in vitro by mechanical trauma to blood.     

Skin autoimmunity and blood coagulation

Evidence exists that the immune and coagulation systems are simultaneously activated in some systemic autoimmune disorders. Although proinflammatory mediators induce tissue factor (TF) expression, the main initiator of blood coagulation, activated proteases of coagulation may act on protease-activated receptors (PAR) triggering inflammation. Such a cross-talk amplifies and maintains the activation of both systems. This review focuses on the involvement of immune and coagulation system in two skin disorders as chronic urticaria (CU), autoimmune in about 45% of cases, and bullous pemphigoid (BP), the prototype of autoimmune blistering diseases. Several investigators demonstrated the activation of coagulation in CU through the involvement of eosinophils, of TF pathway with thrombin generation and increased vascular permeability. Preliminary data indicate that anticoagulant treatment with heparin and warfarin may be effective in reducing the symptoms of this disorder. The activation of coagulation seems to display local and systemic implications in BP. Eosinophils' recruitment and thrombin generation locally contribute to the bulla formation and tissue damage. The systemic activation of coagulation may explain the increased thrombotic risk observed in these patients. Taken together, these data provide the rationale for proposing clinical trials on the anticoagulant treatment in both CU and BP patients.     

淋巴瘤血管内皮细胞人白细胞DR抗原和第Ⅷ因子相关抗原的表达

目的试图揭示人白细胞ＤＲ抗原（ＨＬＡ－ＤＲ）和第Ⅷ因子相关抗原（ＦⅧＲＡｇ）的表达规律,研究血管内皮细胞的生物学行为。方法应用ＨＬＡ－ＤＲ和ＦⅧＲＡｇ的抗血清,对３９例淋巴瘤中血管内皮细胞的功能异质性进行免疫组织化学及其形态定量研究,同时取新生儿、成人淋巴结及反应性增生淋巴结做对照。结果新生儿、成人淋巴结及反应性增生淋巴结内各类血管内皮细胞对ＨＬＡ－ＤＲ、ＦⅧＲＡｇ均呈阳性,其中高内皮后微静脉（ＨＥＶ）呈强阳性;Ｈｏｄｇｋｉｎ病和Ｔ细胞淋巴瘤中血管多数是ＨＥＶ样血管,内皮细胞均表达ＨＬＡ－ＤＲ及ＦⅧＲＡｇ;Ｂ细胞淋巴瘤中血管多数是毛细血管样血管,内皮细胞很少表达或不表达ＨＬＡ－ＤＲ,只表达ＦⅧＲＡｇ。结论说明Ｈｏｄｇｋｉｎ病和Ｔ细胞淋巴瘤中血管内皮细胞既参与免疫调节过程,又参与凝血过程;而Ｂ细胞淋巴瘤内血管内皮细胞只参与凝血过程,不参与免疫调节过程。     

ELF脉冲电磁场对血液粘度和凝血特性的影响

临床研究已证明多种疾病与血液粘度和凝血过程异常有关、高血粘和高凝血导致或加速某些疾病的形成,其中一些疾病的死亡率正逐渐上升.探索降低血液粘度,抑制凝血过快、过强的新方法就成为当今关注的课题.本文所述内容主要包括:ELF脉冲电磁场发生器和XJH-1凝血仪的研制;ELF脉冲电磁场对全血表观粘度和凝血的影响.主要结论有:ELF脉冲电磁场辐照,红细胞表面电荷量增加,全血表观粘度下降(P<0.01),凝血过程减慢,凝血块强度降低(P<0.01),处理间比较脉冲磁场作用效果更好.     

Multiple pathways of cell invasion are regulated by multiple families of serine proteases

The complex process of tumor invasion requires the coordinated expression and activity of cell-substratum adhesive interactions and of cell-associated protease systems, which destroy the extracellular matrix (ECM), in order to enable the invading cells to simultaneously grip and destroy the anatomical barriers that control cell spreading. A number of data indicate that such a `grip and go' process may be performed by an enlarging series of cell membrane-associated serine proteases and serine protease receptors, which provide the invasive cells with a functional unit (the protease and its receptor), able to mediate cell-substratum adhesion through specific receptor domains, to proteolytically degrade ECM and to deliver into the cell signals that up-regulate the expression either of the protease/receptor complex, or of other adhesion molecules, such as integrins. There is evidence that some proteases and protease receptor expression are under the control of tumor hypoxia, which is the result of an imbalance in oxygen supply and demand. The urokinase-type plasminogen activator (u-PA) receptor (u-PAR) is under hypoxic control and cooperates with other serine proteases of the blood coagulation pathways that may extravasate in the tumor milieu as a result of hypoxia-simulated increase of vessel permeability. Other serine proteases and their receptors cooperate with the cell-associated fibrinolytic system to promote cell invasion. Among these, tissue factor and its ligand coagulation factor VII, thrombin and its protease-activated receptors, and type II trans-membrane serine proteases seem to play a crucial role. This Review takes into consideration the complex scenario of the single serine proteases and related receptors that are involved in cell invasion, as well as the protease receptor/adhesion molecule interplay which is necessary to focus the cell surface-driven proteolysis where adhesion provides a grip to the invading cell. This revised version was published online in July 2006 with corrections to the Cover Date.     

凝血瀑布机制中蛋白C作用的动力学模型研究

凝血过程涉及到一系列蛋白因子的反应,上一级的活性蛋白因子裂解下级的蛋白质,使其成为活性的蛋白质,从而使反应继续而形成反应瀑布机制,在凝血反应核心反馈过程中,蛋白C起着至关重要的调节作用.本研究主要探讨在凝血过程中蛋白C的激活和失活过程,活性蛋白C对因子V的作用以及对整个凝血系统的影响.在生理实验的基础上,建立关于凝血蛋白C作用的非线性数学模型,通过系统的定态平衡分析,从理论上证明存在外源性路径启动的触发阈值;通过动态解的数值模拟,研究蛋白C的作用.结果 证实,蛋白C的缺乏对整个凝血系统的影响是微弱的,是否缺乏蛋白C对系统的启动阈值没有影响;但是当蛋白C过量时,IIa的浓度随着时间的延长趋于零,预示凝血系统不能正常启动,蛋白C对IIa有很强抑制作用.以上结果将对血液学理论与临床血液学研究提供有益的启示,也展现出模型化方法对研究凝血系统的预测性能力.     

Red cell membrane CO2 permeability in normal human blood and in blood deficient in various blood groups, and effect of DIDS.

The red cell membrane has an exceptionally high permeability for CO2, PCO2 approximately 0.15 cm/s, which is two to three orders of magnitude greater than that of some epithelial membranes and similarly greater than the permeability of the red cell membrane for HCO3-. As shown previously, this high PCO2 can be drastically inhibited by 10 microM 4,4'-diisothiocyanato-2,2'-stilbenedisulfonate (DIDS), indicating that membrane proteins may be involved in this high gas permeability. Here, we have studied the possible contribution of several blood group proteins to CO2 permeation across the red cell membrane by comparing PCO2 of red cells deficient in specific blood group proteins with that of normal red cells. While PCO2 of normal red cells is approximately 0.15 cm/s and that of Fy(null) and Jk(null) red cells is similar, PCO2's of Colton null (deficient in aquaporin-1) and Rh(null) cells (deficient in Rh/RhAG) are both reduced to about 0.07 cm/s, i.e. to about one half. In addition, the inhibitory effect of DIDS is about half as great in Rh(null) and in Colton null red cells as it is in normal red cells. We conclude that aquaporin-1 and Rh/RhAG proteins contribute substantially to the high permeability of the human red cell membrane for CO2. Together these proteins are responsible for 50% or more of the CO2 permeability of red cell membranes. The CO2 pathways of both proteins can be partly inhibited by DIDS, which is why this compound very effectively reduces membrane CO2 permeability.     

The role of complex formation and epidermal growth factor-like domains in the regulation of blood coagulation by the thrombomodulin-protein C system

The explosive nature of the coagulation cascade led many scientists to investigate how it is regulated. Proteinase inhibitors such as antithrombin III inhibit active proteases of the coagulation cascade. Cofactors such as factor Va and factor VIIIa are proteolytically inactivated by activated protein C. Protein C is activated by the thrombin-thrombomodulin complex on the endothelial cell surface. Thus, the independent actions of the proteinase inhibitor system and the thrombomodulin-protein C system complement each other to maintain regulation of blood coagulation. The thrombin binding site of thrombomodulin was identified to be the fifth and sixth repeats of the epidermal growth factor-like domain. The same binding template contains sufficient information to block the functions of thrombin as a procoagulant. However, additional repeats are required for the activation of protein C. Thrombomodulin is the first example which illustrates that the epidermal growth factor-like domain functions as a binding template for thrombin and as a switch to turn off the procoagulant activity of thrombin as well as to trigger the protein C anticoagulant pathway. Epidermal growth factor-like structures are found in many of the coagulation factors. Complex formation is a repeated theme not only in the blood coagulation cascade but also in the thrombomodulin-protein C anticoagulant pathway.