Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.21.6 (thromboplastin)
13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intravenous administration of BSA into 3-month-old rabbits producing detectable anti-BSA antibody only of the IgE class of immunoglobulin induced a variety of intravascular blood coagulation alterations observed in the plasma 15 min after antigen challenge included: a) the intravascular consumption of intrinsic blood coagulation factors XII, XI, and IX and possibly the reduction in clottable fibrinogen; b) a significant prolongation of the activated partial thromboplastin time but not the prothrombin time; and c) the production of an inhibitor affecting the last stage of blood coagulation. The observed blood coagulation alterations were not caused by the manipulative procedures utilized, the presence of anti-BSA, IgG or IgM antibody, histamine-induced alterations in the vascular endothelium or the development of hypotensive shock. It is proposed that specific IgE antibody can induce directly or indirectly the activation of intrinsic blood coagulation in vivo.
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PMID:IgE-induced blood coagulation alterations in the rabbit: consumption of coagulation factors XII, XI, and IX in vivo. 5 Mar 67

Attempts were made to demonstrate ultrastructural changes of the tissue thromboplastin after intravenous injection, as a model experiment on the pulmonary microthrombi formation induced by the tissue thromboplastin circulating from venous return. Concentrically arranged membrane structures of the injected thromboplastin disappeared in extremely short time after the injection of the thromboplastin in rabbits. The long sheet membrane of the injected thromboplastin was frequently seen as adhered to the vascular endothelium or to the surface of blood corpuscles. Furthermore, fibrin fibres were formed in contact with the long sheet membrane of the thromboplastin. Membrane structures were not found anywhere in the control rabbits.
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PMID:Ultrastructural changes of the tissue thromboplastin after intravenous injection in rabbits. 58 Apr 94

Blood coagulation may be activated by the extrinsic or intrinsic pathways. The extrinsic clotting system is put into action by tissue thromboplastin, originating from injured tissue cells, but also from damaged leukocytes and erythrocytes. Tissue thromboplastin is a phospholipoprotein with an enzymatic component, capable of converting the clotting factor VII to its activated form, factor VIIa, which in turn activates factor X. The factor Xa-complex (containing also factor Va, phospholipid, and calcium) is the prothrombinconverting principle. The intrinsic clotting system is based on factors which are contained in the circulating blood. Its activation requires the availability of phospholipid and of activated factor XII (factor XIIa), or factor XIa. Factor XII is activated by collagen, i.e., whenever the vascular endothelium is injured, and to a lesser extent also by "activated" blood platelets. Platelets in turn are activated primarily by thrombin, collagen, and, in a self-perpetuating process, since all these materials are released from activated platelets, also by adenosine-5-diphosphate, adrenaline, and serotonin. The activation of platelets leads to a variety of morphological and biochemical alterations, culminating in their aggregation and in the selective release from storage organelles of different substances, among them those mentioned above. Of particular importance is the fact that in the course of platelet alterations, procoagulant phospholipid also becomes available on the platelet surface. The significance of the activation of the intrinsic system is seen in the possibility of the initiation of a self-sustained process which, after a primary event, e.g. vascular or cellular injury, will continue to convert prothrombin into thrombin. The effects of endotoxin on the blood clotting system show striking species differences. In the rabbit, endotoxin, with the involvement of factors of the complement system, will directly act upon blood platelets and thus initiate intravascular, intrinsic coagulation. In man, endotoxin remains without a direct effect on platelets and alternative possibilities of initiating thrombin formation must be considered. One possibility is extrinsic activation via tissue thromboplastin from injured leukocytes. Another pathway, which is supported by several experimental findings, starts out with endotoxin-mediated endothelial damage. Endothelial cells are in fact severely affected by endotoxin and may even be removed from the vascular wall, thus making accessible the subendothelial activator of factor XII. Thrombin in turn affects the vascular endothelium: therefore, one initiated, the process of intravascular activation of coagulation will perpetuate, this the more as platelets in turn will be stimulated into activity. The possible intervention of other vasoactive factors must also be considered...
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PMID:[Activation of the blood coagulation system during gram-negative infections and endotoxemias]. 122 91

Antiphospholipid antibodies can be detected by three methods; agglutination reactions with a cardiolipid antigen (VDRL, Kline, Kolmer) as observed in false positive syphilitic serologies; secondly coagulation reactions using thromboplastin (activated cephalin time, diluted thromboplastin time, Stipven time...). These cases are called lupus-like or, better, antiprothrombinase circulating antibody; finally, solid phase immunological tests (ELISA, RIA) with purified phospholipids, usually cardiolipin. The antiphospholipid antibodies detected by this method are not the same and the percentage of concordance between the two tests does not exceed 50 per cent. These antibodies are present in 30 to 60 per cent of patients with disseminated lupus erythematosus and also, less frequently, in other connective tissue disorders. They are always found in the so-called primary antiphospholipid syndrome, featuring recurrent venous or arterial thrombosis, repeated abortion, thrombocytopenia, and often a livedo reticularis and leg ulceration. Arterial thrombosis may occur in any part of the body (eye, central nervous syste, visceral or peripheral arteries). Mortality is related to neurological or coronary complications. The pathogenicity of antiphospholipid antibodies has not been formally demonstrated, but they could interact with membrane phospholipids of the vascular endothelium and/or platelets. Immuno-suppressor therapy is not very effective and long-term anticoagulant and/or platelet antiaggregant therapy is usually required.
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PMID:[Anticardiolipin antibody in peripheral arterial diseases]. 176 82

High-dose interleukin-2 (IL-2) immunotherapy can cause hypotension, respiratory distress, interstitial edema, and thrombocytopenia, similar to endotoxic shock. We have observed that IL-2 has no direct effect on coagulation factors in vitro, but it has been observed to alter the coagulant properties of vascular endothelium. Accordingly, we investigated the possibility that IL-2 infusions initiate plasma fibrinolysis and disseminated intravascular coagulation (DIC). We studied the clinical course, platelet count, and coagulation profile in response to IL-2 infusion in seven patients, two with metastatic melanoma and five with metastatic renal cell carcinoma. Every patient experienced hemodynamic instability and thrombocytopenia, and one patient suffered an unusual complication, mesenteric thrombosis. No patient had appreciable changes in the prothrombin time or the partial thromboplastin time, nor did factors V or VIII decline in the two patients observed. In four patients examined, we found decreased titers of Hageman factor (factor XII), high molecular weight kininogen, prekallikrein, and plasma thromboplastin antecedent, as if these had been consumed by reactions of the intrinsic pathway of thrombin formation. Circulating D-dimer fragments were found in the plasma of every patient at some point during each infusion cycle, and we observed decreased titers of plasminogen in the four patients just mentioned, suggesting that IL-2 infusions initiated fibrinolysis. Taken together, the clotting factor derangements and related toxicity phenomena cannot be ascribed firmly to DIC. Activation of the intrinsic (contact) system of coagulation, however, may provide one link between the vascular endothelial surface alterations caused by IL-2 infusions and the development of the systemic toxicity that resembles septic shock.
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PMID:Fibrinolysis, thrombocytopenia, and coagulation abnormalities complicating high-dose interleukin-2 immunotherapy. 198 12

Human vascular endothelium plays a major role in hemostatic processes. Human venous endothelial cells (HEC) may promote coagulation by generation of thromboplastin. This tissue factor production is enhanced by bacterial lipopolysaccharide (LPS). However, the mechanisms of this enhancement remain unclear. In order to quantify by image analysis the nuclear modifications induced by LPS on HEC, umbilical cord vein HEC were cultured in vitro with or without E. coli LPS (10 micrograms/ml) for 0 to 6 h. At the end of culture, tissue factor expression was evaluated by the ability of a cellular extract to shorten the coagulation time of human citrated plasma. Simultaneously, the morphology of LPS treated and control HEC was analysed using a SAMBA 200 cell image processor after Feulgen staining. This analysis indicates that LPS treatment induces nuclear modifications as early as 1 h after culture onset, before any tissue factor expression. This activity appears only between 2 and 4 h of culture with LPS. Our data show that image analysis permits the detection of very early nuclear events in HEC and that these events precede the expression of functional properties which may be implicated in thrombotic processes.
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PMID:Nuclear textural changes preceding endotoxin mediated enhancement of thromboplastin synthesis in human endothelial cells in vitro. 227 59

The plasma proteinase inhibitors are relatively ineffective in the inhibition of the activity of the platelet prothrombinase complex, due to the low rates of inhibition, and possibly due to the indirect protection from the potentiating effect of the vascular endothelium. The plasma proteinase inhibitors are more effective at inhibiting thrombin, thereby preventing the feedback activation of platelets and factor V and subsequent prothrombinase complex development. This may constitute a mechanism for the control of the development of the prothrombinase complex on the platelet surface. The protein C-thrombomodulin mechanism for the destruction of factor Va activity probably constitutes a major inhibitory mechanism for the prothrombinase complex in vivo.
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PMID:Mechanisms of inhibition of platelet coagulant activity. 242 87

A complex series of reactions are involved in the assembly, function, and regulation of the prothrombinase complex. Since the enzyme is multicomponent in nature and each component is required for catalytic function, modulation of enzymatic activity can be achieved in a variety of ways. In addition, since complex assembly so profoundly affects reaction rates, mechanisms that perturb complex formation either positively or negatively have a profound effect on thrombin generation and its local physiologic effects. All of the cells that support prothrombinase assembly and hence thrombin generation respond to thrombin in a variety of ways. Thrombin selectively binds to thrombomodulin and heparin-like molecules expressed on the endothelial cell surface. Thrombin induces the release (and possible synthesis of) prostacyclin, plasminogen activator inhibitor, platelet-derived growth factor, and interleukin-1 and inhibits the release of plasminogen activator from vascular endothelium. Interleukin-1 is a potent mediator of inflammatory phenomena as well as an inducer of tissue factor synthesis in vascular endothelium. With respect to platelets, thrombin selectively binds and stimulates the platelet release reaction and subsequent aggregation. The thrombin-induced release of platelet-derived growth factor from both platelets and vascular endothelium may play a role in inflammation, wound healing, and atherogenesis. Thrombin itself is a potent mitogen of mesenchymal cells, and more recently has been shown to be not only a chemoattractant, but also a mitogen for monocytes. Thrombin also appears to bind selectively to monocytes and in so doing induces release of interleukin-1. Thrombin affects a myriad of cellular responses related to hemostasis, thrombosis, inflammation, would repair, and atherogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of thrombin generation at cell surfaces. 305 86

In the present paper some of the characteristics of the pharmacodynamics of low-molecular-weight (LMW) heparin and the importance of the inhibition of the factor Xa are outlined. In summary, there is some evidence that the inhibition of factor Xa mediated fibrin formation and antithrombotic effects. However, there is a lot of experimental evidence that heparin and LMW heparins induce antithrombotic effects by releasing compounds from vascular endothelium, too. Thus, distinct interactions of heparin and LMW heparins with the cellular compounds of the blood may modulate the antithrombotic and hemorrhagic capacities.
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PMID:Relation of antifactor Xa activity of heparins and antithrombotic efficacy. 329 27

In blood coagulation on endothelium, an unperturbed vascular endothelial cell surface apparently provides activity equivalent to the phospholipid needed for generation of factor Xa and thrombin in soluble systems. Phospholipid in soluble systems also markedly enhances the ability of factor Xa to activate factor VII; therefore we investigated the influence of an unperturbed monolayer of human umbilical vein endothelial cells (HUVEC) upon factor VII activation. HUVEC were found to augment factor Xa-catalyzed activation of factor VII. This appeared to result from the binding of trace amounts of factor Xa to the cells. Adding active site-inhibited factor Xa to reaction mixtures, but not factor X, abolished the enhanced activation. Adding either anti-factor V antibodies or exogenous factor Va had no effect upon reaction rates. Thus factor Va does not function as a cofactor for the reaction. In further experiments the effect upon activation of factor VII and prothrombin was studied by varying the order of addition of factor Xa and factor Va to supernatants of HUVEC monolayers. Evidence was obtained that HUVEC, unlike platelets, possess a functional factor Xa binding site that is independent of factor Va. Since phospholipid is the only known cofactor for factor Xa/Ca2+-induced activation of factor VII, the demonstration of enhanced activation of factor VII in the presence of unperturbed cultured HUVEC supports a hypothesis that the functional equivalent of procoagulant phospholipid is available on the luminal surface of vascular endothelium in vivo.
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PMID:Enhancement by human umbilical vein endothelial cells of factor Xa-catalyzed activation of factor VII. 342 31


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