Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012739 (disseminated intravascular coagulation)
 8,673 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Danaparoid and heparin, on the basis of anti-activated factor X (anti-FXa) activity, were equipotent in accelerating the rate of interaction of FXa and antithrombin III. In rat tissue factor-induced disseminated intravascular coagulation (DIC) models, an intravenous administration of danaparoid inhibited the decrease in plasma fibrinogen and platelet counts and the increase in serum fibrinogen degradation products. Expressed on the basis of anti-FXa activity, these effects were comparable with those of dalteparin and heparin. In rat mesenteric small artery and vein, less bleeding was observed after intravenous administration of danaparoid than after dalteparin or heparin. Danaparoid did not affect adenosine diphosphate- or collagen-induced platelet aggregation, and showed weaker inhibitory effects on aggregation induced by thrombin, or collagen + thrombin, than did dalteparin or heparin. These findings suggest that danaparoid may be useful for the prevention of DIC and has less tendency to cause bleeding than dalteparin or heparin, probably as a result of its weaker ability to inhibit platelet aggregation.
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PMID:The effects of danaparoid, dalteparin and heparin on tissue factor-induced experimental disseminated intravascular coagulation and bleeding time in the rat. 1150 77

Oxidative stress results from an oxidant/antioxidant imbalance, an excess of oxidants and/or a depletion of antioxidants. A considerable body of recent evidence suggests that oxidant stress plays a major role in several aspects of septic shock and disseminated intravascular coagulation (DIC), and it is the subject of this review. Immunohistochemical and biochemical evidence demonstrate the significant role of reactive oxygen species (ROS) in endotoxic and hemorrhagic shock, and in endothelial injury associated with DIC syndrome. Initiation of lipid peroxidation, direct inhibition of mitochondrial respiratory chain enzymes, inactivation of glyceraldehyde-3-phosphate dehydrogenase, inhibition of membrane Na+/K+ ATP-ase activity, inactivation of membrane sodium channels, and other oxidative protein modifications contribute to the cytotoxic effect of ROS. In addition, reactive oxygen species are potent triggers of DNA strand breakage, with subsequent activation of the nuclear enzyme poly-ADP ribosyl synthetase, with eventual severe energy depletion of the cells. Pharmacological evidence suggests that the peroxynitrite-poly-ADP ribosyl synthetase pathway contributes to the cellular injury in shock and endothelial injury. Treatment with superoxide dismutase mimetics (SODms), which selectively mimic the catalytic activity of the human superoxide dismutase enzymes, have been shown to prevent in vivo shock and the cellular energetic failure associated with shock.
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PMID:Oxidative stress in septic shock and disseminated intravascular coagulation. 1239 25

Higenamine (HG) is a potent cardioactive benzylisoquinoline alkaloid isolated from Aconiti tuber which has long been used as a cardiotonic in traditional Chinese medicine. HG exerts various effects on the cardio-circulatory system inotropic and chronotropic in isolated rat atria. It also relaxes isolated rat aorta. It inhibits epinephrine, ADP or collagen-induced platelet aggregation in platelet rich plasma. HG inhibits LPS-induced nitrate accumulation and the expression of iNOS mRNA in RAW 264.7 cells. HG lowers blood pressure in rats and increases the recovery rates in acute thrombosis model of mice, and lower the weight of thrombus formed in the arterio-venous shunt model of rats. Higenamine also has ameliorative effects in the LPS-induced DIC model.
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PMID:[Effects of higenamine on the cardio-circulatory system]. 1562 Jan 76

A study was conducted on the changes in platelet function and platelet count in the Sprague-Dawley rat induced by a bends-producing N2-O2 compression-decompression cycle. In those instances where mild to moderate cases of decompression sickness were produced, a decrease in platelet reactivity to ADP-induced aggregation occurred immediately postdive along with an increase in inhibition of aggregation by prostaglandin E1. Both effects returned to control levels 24 hours postdive. In moderately affected animals, platelet counts were lower than normal 24 hours postdive but were similar to control values 72 hours postdive. These results tend to support current hypotheses regarding the etiological relationship between disseminated intravascular coagulation and decompression sickness as a function of bubble nucleation.
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PMID:Supportive evidence for altered platelet function in the dived rat. 1562 36

Platelet recruitment crucially depends on amplification systems provided by autocrine and paracrine factors such as adenosine diphosphate. In inflammatory states, consumption of coagulation proteins, such as antithrombin aggravates the procoagulant state. In this study, we report that platelets express syndecan-4, an antithrombin-binding cell surface heparan sulphate proteoglycan, whose ligation with antithrombin inhibits activated platelet-dependent superoxide anion release from neutrophils by the limitation of adenosine diphosphate and adenosine triphosphate secretion in activated platelets. Adenosine triphosphate-induced platelet aggregation is reduced after treatment of platelets with antithrombin, which is reversed by blockade of syndecan-4. We further observed that antithrombin limits CD40 ligand expression in adenosine diphosphate-activated platelets and inhibits the shedding of syndecan-4 from activated platelets. Syndecan-4 appears to be directly involved in regulating platelet aggregation as anti-syndecan-4 antibody augments platelet aggregation. We suggest that antithrombin might exert beneficial effects in disseminated intravascular coagulation by reducing platelet activation, observed as inhibited CD40 ligand expression, syndecan-4 shedding, and adenosine diphosphate- and adenosine triphosphate-release from activated platelets with subsequent inhibition of neutrophil respiratory burst. From these data it is concluded that syndecan-4 may play important roles in the regulation of inflammatory effects of platelets.
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PMID:Expression and function of syndecan-4 in human platelets. 1596 98

The anti-thrombic properties of the Korean herbal medicine, Dae-Jo-Hwan (DJW), which is consisted of 11 herbs (indicated as concentrations) of Rehmanniae radix 24%, Hominis placenta 5%, Testudinis carapax 9%, Eucommiae cortex 9%, Asparagi radix 9%, Phellodendri cortex 9%, Achyranthis radix 7%, Liriopis tuber 7%, Angelicae sinensis radix 7%, Ginseng radix 6%, and Schizandrae fructus 3%, were investigated. The extracts of DJW and its 11 herbs, except G. radix, A. sinensis radix and S. Fructus, inhibited the endotoxin-induced hepatic venous thrombosis in high cholesterol diet-treated rats. Also the extract inhibited the endotoxin-induced decrease in blood platelets and fibrinogen, and endotoxin-induced increase in fibrin degradation products (FDP) on disseminated intravascular coagulation in normal rats. In in vitro experiments, the extract was shown to have inhibitory effect on collagen- and ADP-induced blood platelet aggregation, on thrombin-induced conversion of fibrinogen to fibrin and on the activity of plasminogen or plasmin. In conclusion, the protection of extracts of Korean herbs on the ischemic infarction induced artificially might be related to their inhibitory effects on DIC, platelet coagulation and thrombic action.
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PMID:Anti-thrombic activity of Korean herbal medicine, Dae-Jo-Whan and its herbs. 1622 22

Inappropriate platelet activation is a feature of acute and chronic diseases such as disseminated intravascular coagulation (DIC) and atherosclerosis. Since proinflammatory microbial-derived agonists can be involved in the pathogenesis of these diseases, we examined the potential role of TLR4 (mediating responses to LPS) and TLR2 (which responds to bacterial lipopeptides) in platelet activation. Our data suggested low-level expression of TLR2 and TLR4 on platelets, determined by flow cytometry, and we also observed expression of TLR4 on a megakaryocytic cell line by both flow cytometry and immunohistochemistry. Stimulation of the platelets with the TLR4 agonist LPS, and the synthetic TLR2 agonist Pam3CSK4, resulted in no platelet aggregation, no increase in CD62P surface expression and no increase in the cytosolic concentration of Ca2+. The TLR agonists were also unable to directly activate platelets primed with epinephrine, or pretreated with a low concentration of ADP or PAF. Pretreatment of platelets with LPS or Pam3CSK4 also failed to modulate the platelet response to submaximal concentrations of the classical platelet agonists ADP and PAF. We conclude that the TLR agonists LPS and Pam3CSK4 have no direct effect on platelet activation and that platelet TLRs may be a remnant from megakaryocytes. TLR2 and TLR4 agonists are thought to have a significant role in diseases such as atherosclerosis and DIC, but our research suggests that this is through a mechanism other than direct platelet activation or by modification of platelet responses to other agonists.
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PMID:Agonists of toll-like receptor (TLR)2 and TLR4 are unable to modulate platelet activation by adenosine diphosphate and platelet activating factor. 1627 Jun 39

Platelet aggregation was undertaken in platelet rich plasma in 34 heat-stroke patients during the Muslim pilgrimage (Haj) to Makkah; 18 were males and 16 were females; their ages ranged from 36 to 80 years (mean SD = 58 10). Platelet aggregability, on arrival at the Heatstroke Centres, was markedly inhibited in response to adrenaline, collagen, arachidonic acid and ristocetin but not to ADP. Responses to decreasing ADP doses (20.0, 2.0, 1.0 and 0.5 micromol/l) showed hyperaggregability in 12 patients, inhibited responses in 16 and normal responses in 6 patients. Aggregation responses were not significantly different when comparing patients with bleeding manifestations ( n = 10), with those without bleeding ( n = 24). Haemostatic parameters including plasma fibrinogen, ATIII and platelet count, were markedly reduced in the two patient groups who showed hyperaggrebable and depressed aggregation responses, but not in those with normal responses. These results lead us to conclude that: (1) platelet activation is a frequent feature of heatstroke; (2) in heatstroke altered aggregation responses, whether hyperaggregable or depressed, occur simultaneously with a consumption coagulopathy.
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PMID:The role of platelets in the coagulopathy of heatstroke- a study of platelet aggregation in heatstroke patients during the Makkah pilgrimage (Haj) to Makkah. 1679 31

Endotoxin or bacterial lipopolysaccharide (LPS) is a structural component of Gram-negative bacteria. It is believed to be the major pathogenic factor of Gram-negative sepsis, and may result in intravascular coagulation and in a shock syndrome that is characterized by thrombocytopenia, leucopenia, hypotension, fever, reduced delivery of oxygen, metabolic acidosis and ultimately death. We have previously shown that both endotoxemic pigs and patients with Gram-negative sepsis have elevated levels of platelet microvesicles in their blood, which indicates platelet activation. In this study, we have used flow cytometry and fluorescein-labeled chicken anti-human fibrinogen to evaluate the in vivo effect of endotoxin on platelet function in a porcine model. Endotoxin infusion in pigs caused impaired platelet function when platelets were stimulated with adenosine-diphosphate in vitro ( P < 0.001). We also found a similarly decreased platelet function in patients with Gram-negative sepsis. Since flow cytometry is a rapid method for determination of platelet function, this method may turn out to be a useful tool in clinical situations. Our results may contribute to our understanding of the bleeding problems that may occur in septic shock and in disseminated intravascular coagulation.
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PMID:Impaired platelet function in endotoxemic pigs analyzed by flow cytometry. 1679 86

Patients with sepsis often suffer from haemostatic disturbances such as haemorrhage and disseminated intravascular coagulation (DIC). Considering the pivotal role of platelets in haemostasis, we have investigated platelet function by flow cytometry in 16 patients with sepsis for a better understanding of their haemostatic function. We have also investigated whether platelet function correlates with the severity of disease assessed by multiple organ dysfunction (MOD) score and patient outcome. The platelet response ex vivo after stimulation with agonists, measured as platelet fibrinogen, binding was low in comparison with healthy volunteers ( n = 30). This could reflect a previous response to agonists in vivo , which lead to platelet activation and consumption and formation of microthrombi that could then participate in the development of M OD. The platelets that remain in the circulation might be the result of a selection process where the most active platelets have already been consumed, and the remaining population consists of less active platelets. Another explanation might be desensitization of the remaining platelets because of exposure to agonists in vivo . Platelet activation with the agonists ADP and arachidonic acid were predictive of subsequent development of MOD and final patient outcome.
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PMID:Impaired platelet function correlates with multi-organ dysfunction. A study of patients with sepsis. 1679 6


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