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Query: UMLS:C0012739 (disseminated intravascular coagulation)
 8,673 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sepsis or septic shock is frequently associated with activation of the complement system, coagulation and fibrinolytic changes and the release of several cytokines. In this study we analyzed the relation of complement activation to the inflammatory mediators, hemodynamic and biochemical parameters and severity of illness and outcome in 20 consecutive patients with clinically defined sepsis. Levels of C3a and C3d were elevated in 90% of the patients (median levels 0.19 mg/l and 8.6 mg/l respectively) in comparison to 14% and 42%, respectively of 7 patients with non-septic shock. Levels of C4 were decreased in only 1 of the 20 septic patients. Levels of TNF and IL-6 were elevated in 94% and 100% of the patients, Levels of TNF and IL-6 were elevated in 94% and 100% of the patients, respectively (median levels 122 ng/l and 1300 U/ml) and were clearly interrelated (r = 0.67, p less than 0.01). C3a levels correlated with the APACHE II score (r = 0.57, p less than 0.05) and high C3a levels were associated with fatal outcome (p less than 0.05). C3a was also correlated inversely with mean arterial pressure (r = 0.50, p less than 0.01). Levels of complement C3a and C3d significantly correlated with levels of plasminogen activator inhibitor-1 (PAI) and correlated inversely with AT-III levels. We found no correlation between these complement products and leukocyte counts or lactate levels, nor was there a correlation between C3a or C3d and the cytokines TNF and IL-6. Levels of C3a and C3d did not decrease significantly during the first 24 h of treatment, in contrast to a clear decrease in IL-6 levels in all patients and a decrease in TNF in the surviving patients. TNF levels remained stable or increased in the non-survivors. We conclude that both the complement system and the cytokine system are involved in the pathogenesis of septic shock and may be involved in the development of some of the fatal complications like hypotension and disseminated intravascular coagulation.
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PMID:Complement activation and the production of inflammatory mediators during the treatment of severe sepsis in humans. 164 97

We have reported earlier that immunodepletion of extrinsic pathway inhibitor (EPI) sensitizes rabbits to disseminated intravascular coagulation (DIC) induced by infusing a low concentration of tissue factor (TF). We now describe the effect of immunodepletion of EPI in rabbits administered endotoxin. Cortisone-treated rabbits were administered anti-rabbit EPI immunoglobulin (IgG) or Fab fragments or were administered control nonimmune material before an injection of endotoxin. In four of seven rabbits administered anti-EPI, plasma EPI activity levels were reduced by 70% to 80% of initial levels for 6 to 8 hours. In these rabbits the endotoxin induced extensive DIC, as evidenced by substantial decreases in fibrinogen, factor V, factor VIII, and platelets, and gross hemorrhagic necrosis of the kidneys due to massive deposition of fibrin in the glomerular microcirculation (the generalized Shwartzman reaction). In three rabbits administered anti-EPI, plasma EPI levels were only transiently reduced. In these rabbits and in four rabbits administered nonimmune IgG or Fab, endotoxin induced minimal to moderate intravascular clotting and deposits of fibrin were not found in the glomerular capillaries. Because it is believed that TF expressed on monocytes triggers endotoxin-induced coagulation, these data are taken as evidence that EPI functions as a natural anticoagulant that can regulate factor VIIa/TF activity expressed on cell surfaces in vivo. They support a hypothesis that EPI prevents thrombotic complications that might otherwise result from exposure of blood to cytokine-induced generation of small amounts of TF on cell surfaces in many inflammatory and infectious disease states.
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PMID:Immunodepletion of extrinsic pathway inhibitor sensitizes rabbits to endotoxin-induced intravascular coagulation and the generalized Shwartzman reaction. 190 95

Previously we studied levels of the cytokine IL-6 and activation of the complement and contact system and of neutrophils in a group of 48 patients with sepsis. Some of these inflammatory parameters appeared to be associated with a poor prognosis. Here we report on the relationships of C4a and C3a (complement activation products), of factor XII and prekallikrein (contact system proteins), of elastase (a protease released by activated neutrophils) and of the cytokine IL-6 to hemodynamic and biochemical parameters measured in those 48 patients at the time of admission to the Intensive Care Unit. No significant correlations between any inflammatory parameter and either systemic vascular resistance or cardiac index were found. Mean arterial pressure significantly correlated with both factor XII and prekallikrein levels. Lactate correlated with C3a and C4a, with elastase, and in particular, with IL-6, whereas it did not correlate with either factor XII or prekallikrein. Platelet numbers inversely correlated with both C3a and C4a, as well as with elastase and IL-6, whereas they positively correlated with factor XII and prekallikrein. Based on these findings we propose a model for the interplay of these inflammatory mediators in the pathogenesis of sepsis. This model takes into consideration the occurrence of capillary leakage, shock, disseminated intravascular coagulation, thrombocytopenia and of acute phase reactions in sepsis.
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PMID:A model for the interplay of inflammatory mediators in sepsis--a study in 48 patients. 228 88

We examined red cell fragmentation syndrome (RCFS) induced by mitomycin C (MMC) (13 patients), by thrombotic thrombocytopenic purpura (TTP) (17 patients), and by disseminated intravascular coagulation (DIC) (15 patients). Plasma cytokine levels were increased in the TTP and DIC patients, but not in those whose RCFS was induced by MMC, suggesting that the activation of the immune system plays an important role in the pathogenesis of RCFS due to TTP and DIC but did not in RCFS due to MMC. Plasma thrombomodulin, tissue type plasminogen activator, and plasminogen activator inhibitor-I levels were increased in all RCFS patients, suggesting that RCFS, whether MMC induced, or due to TTP or DIC, might be associated with vascular endothelial cell injury. In TTP, von Willebrand factor (vWF) antigen and high molecular weight vWF multimer levels were reduced, possibly as a result of microthrombus consumption. The hemostatic data in this study showed that the TTP patients were in a hypercoagulable state without hyperfibrinolysis, and that DIC patients were in both a hypercoagulable and a hyperfibrinolytic state, whereas hemostatic abnormalities were slight in patients with MMC induced RCFS. These findings suggest that vascular endothelial cell injuries might be associated with RCFS, and that those injuries in MMC-induced RCFS might not be related to microthrombi or an activated immune system.
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PMID:Hemostatic abnormalities and increased vascular endothelial cell markers in patients with red cell fragmentation syndrome induced by mitomycin C. 748 97

Severe thrombocytopenia and clinical bleeding remain major clinical problems in leukemic patients undergoing remission induction and those receiving high dose chemotherapy. Prophylactic platelet transfusions have made a major impact on hemorrhagic deaths over the last 20 years. The effectiveness of platelet transfusions is influenced by a number of clinical factors including the status of the spleen, prior bone marrow transplantation, the presence of disseminated intravascular coagulation and the presence of HLA antibodies. Optimal platelet transfusion therapy requires that transfusions be monitored routinely by post-transfusion counts and that a refractory group be clearly defined. The cytokine granulocyte colony stimulating factor (G-CSF) has not had a clinically significant impact on thrombocytopenia. Granulocyte-macrophage colony stimulating factor (GM-CSF) also probably has little clinical relevance, although in a randomized study, thrombocytopenia was worse in GM-CSF-treated patients. Interleukin-3 (IL-3) can increase platelet count and has the potential to protect against thrombocytopenia in patients receiving chemotherapy. This hypothesis is currently being tested in on-going clinical trials.
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PMID:Platelet support and the use of cytokines. 752 92

Circulating concentrations of the proinflammatory cytokine leukemia inhibitory factor (LIF) were prospectively determined by radioreceptor competition assay (sensitivity, 1 ng/mL) in 33 subjects with meningococcemia. LIF was detected in the plasma of 13 subjects and was associated with development of septic shock (P < .01), disseminated intravascular coagulation (P < .05), multiorgan failure (P < .05), and death (P < .01). Plasma LIF concentrations were highest (1-1772 ng/mL) at hospital admission and became undetectable within 36 h, and the peak levels correlated inversely with systolic blood pressure (r, -.70, P < .001), peripheral blood leukocyte count (r, -.58, P < .01), and prodromal interval (r, -.60, P < .001). Plasma LIF concentrations > 400 ng/mL were present only in subjects with fatal fulminant infection. LIF concentrations in plasma collected within 12 h of hospital admission correlated with disease severity in patients with meningococcemia. It is likely that LIF participates in the host response to infection, and it may contribute to the pathogenesis of septic shock.
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PMID:Circulating leukemia inhibitory factor levels correlate with disease severity in meningococcemia. 796 17

To investigate the role of neutrophil activation in the pathophysiology and sequelae of disseminated intravascular coagulation (DIC), we measured plasma levels of granulocyte elastase-alpha 1-proteinase inhibitor complex (GEPIC) in 41 patients with DIC and 27 patients with similar underlying conditions but without DIC. Mean GEPIC levels were significantly higher in patients with DIC (421.0 +/- 45.6 ng/ml) than in patients without DIC (246.1 +/- 41.9 ng/ml, P < 0.01). Significant differences were also noted in DIC patients with or without infection (474.7 +/- 61.2 ng/ml vs. 302.4 +/- 48.9 ng/ml, P < 0.04), with or without organ dysfunction (546.6 +/- 72.7 ng/ml vs. 305.6 +/- 42 ng/ml, P < 0.01), and with or without respiratory failure (640.0 +/- 91.2 ng/ml vs. 328.1 +/- 55.1 ng/ml, P < 0.01). No significant difference was found in mean GEPIC levels in DIC patients with or without renal failure, heart failure, hepatic failure, or gastrointestinal bleeding. The frequency of respiratory failure correlated with rising plasma levels of GEPIC. Mortality was higher in patients with GEPIC levels > 500 ng/ml (53.8%) than in patients with GEPIC levels < 500 ng/ml (28.6%). This correlation was particularly strong in patients with DIC, infection, and respiratory failure. Based on these data, we suggest that neutrophil activation, triggered by the coagulation cascade and perhaps augmented by endotoxin or cytokine release with infection, significantly contributes to respiratory failure and mortality in patients with DIC.
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PMID:Plasma levels of granulocyte elastase-alpha 1-proteinase inhibitor complex in patients with disseminated intravascular coagulation: pathophysiologic implications. 809 45

Disseminated intravascular coagulation, characterized by circulating fibrin(ogen) degradation products (FDP), is associated with both acute and chronic inflammatory conditions. Since the association of FDP with monocytes could influence the release of cytokines and other regulatory proteins with significant clinical ramifications, we have studied cytokine synthesis and release following the interaction of D-dimer (DD), a terminal degradation product of fibrin, with human monocytes in vitro. Adherent peripheral blood monocytes were incubated with purified DD for 24 and 48 h and secreted or cell-associated IL-1 beta and IL-6 antigen levels and activity determined. DD (50 micrograms/ml) boosted the secretion of IL-1 beta antigen from median control levels of 659 pg/ml to 2704 pg/ml and that of IL-6 antigen from 806 pg/ml to > 3000 pg/ml at 48 h (P < 0.05). Similar increases in extracellular biologically active IL-1 and IL-6 were observed. Although DD increased cell associated IL-1 beta antigen levels from median values of 188 to 1600 pg/106 cells and IL-6 antigen from 660 to 2215 pg/106 cells (P < 0.05), cell-associated IL-1 functional activity decreased from control levels of 98 inhibitor units/ml to 65 units/ml for cells exposed to DD. Secreted plasminogen activator inhibitor (PAI) bioactivity and PAI type 2 antigen levels were significantly increased following exposure of monocytes to DD. This may explain the decreased cell associated IL-1 activity observed in our study as PAI are known to inhibit biologically active membrane bound IL-1. Our finding that DD enhances monocyte release of biologically active cytokines suggests the presence of positive feedback pathways for fibrinogen synthesis by hepatocytes. Furthermore, the association of monocytes with DD may potentiate localized coagulation processes by subsequent alterations in pericellular proteolysis.
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PMID:Fibrin degradation product D-dimer induces the synthesis and release of biologically active IL-1 beta, IL-6 and plasminogen activator inhibitors from monocytes in vitro. 819 21

In Gram-negative septic shock, human monocytes synthesize and express on their cytoplasmic membrane tissue factor (TF), a potent activator of the coagulation cascades. The role of TF in triggering disseminated intravascular coagulation (DIC) in these patients appears to be clear. We report the suppressive effect of interleukin-10 (IL-10) on endotoxin-induced TF activity and antigen levels, and on the expression of TF mRNA levels in human monocytes. These results emphasize the potential therapeutic value of this cytokine in septic shock, a condition still associated with a high mortality rate.
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PMID:Interleukin-10 inhibits endotoxin-induced tissue factor mRNA production by human monocytes. 822 11

Overwhelming bacterial infection is accompanied by fever, hypotension, disseminated intravascular coagulation, and multiple organ failure leading to death in 30-80% of cases. These classical symptoms of septic shock are caused by potent cytokines that are produced in response to endotoxin released from Gram-negative bacteria. Treatments with antibodies and receptor antagonists to block endotoxin or cytokine mediators have given mixed results in clinical trials. High density lipoprotein (HDL) is a natural component of plasma that is known to neutralize endotoxin in vitro. We report here that raising the plasma HDL concentration protects mice against endotoxin in vivo. Transgenic mice with 2-fold-elevated plasma HDL levels had more endotoxin bound to HDL, lower plasma cytokine levels, and improved survival rates compared with low-HDL mice. Intravenous infusion of HDL also protected mice, but only when given as reconstituted HDL prepared from phospholipid and either HDL apoprotein or an 18-amino acid peptide synthesized to mimic the structure of apolipoprotein A-I of HDL. Intact plasma HDL was mildly toxic, and HDL apoprotein was ineffective. The effectiveness of the reconstituted peptide renders very unlikely any significant contribution to protection by trace proteins in apo-HDL. These data suggest a simple leaflet insertion model for binding and neutralization of lipopolysaccharide by phospholipid on the surface of HDL. Plasma HDL may normally act to protect against endotoxin; this protection may be augmented by administration of reconstituted HDL or reconstituted peptides.
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PMID:In vivo protection against endotoxin by plasma high density lipoprotein. 826 67


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