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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alterations of the coagulation system that may lead to coagulation activation and thrombosis are common sequelae after allogeneic bone marrow transplantation (BMT). We performed prophylactic anticoagulation by low dose heparin (50 units/kg/day) and substitution of antithrombin (AT) concentrate to sustain plasma levels above 90% of pooled normal human plasma. Conventional tests for plasmatic hemostasis and substitution of AT concentrate were recorded for 50 patients until day +50 after BMT. Incidence of sepsis, graft-versus-host-disease [GVHD], capillary leakage syndrome [CLS] and veno-occlusive disease of the liver [VOD] were investigated and compared with the results of patients without any of these complications. Patients with proven sepsis (n = 6) showed decreased activity of AT, and a prolonged activated partial thromboplastin time (aPTT), while fibrinogen levels were slightly increased. This constellation was interpreted as mild to moderate activation of the humoral coagulation cascade. Patients with VOD (n = 10) showed an increased consumption of AT concentrate at day +7 followed by a decrease of prothrombin time, of clotting factors II and VII, and a prolongation of aPTT at days +11 to +18 after BMT. This suggests, that activation of coagulation precedes decreased synthesis of coagulation factors. Patients with CLS (n = 15) or GVHD > or = II degree (n = 14) showed no major alterations of coagulation parameters. In conclusion, after BMT, two types of coagulopathy were observed: (i) an activation of the coagulation cascade (i.e. sepsis and VOD) which was followed by (ii) a diminished synthesis of coagulation factors (VOD). In order to perform timely therapeutic interventions in the coagulation system in patients with sepsis and/or VOD it appears to be important to assess the clinical value of parameters for early detection of coagulation activation as thrombin-AT complexes, D-dimers and F1 + 2 fragments.
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PMID:Humoral coagulation and early complications after allogeneic bone marrow transplantation. 929 52

Cyclosporine toxicity is still a significant problem in the early period after liver transplantation. The monoethylglycinexylidide (MEGX) test performed in the donor has been suggested as a reliable test to predict liver graft function in the recipient. The MEGX test was performed in 50 consecutive donors, and the clinical course of recipients, metabolic parameters of the grafts, and cyclosporine levels were followed in detail for 10 days. Two patients died of sepsis and were excluded. Renal and/or neurological toxicity appeared in 15 of the remaining 48 patients (31%). In the 6 with neurological problems, MEGX values were low (41, 47, 50, 60, 94, and 101 micrograms/L). Nine patients had transient elevations of creatinine and urea; in 8 of these, cyclosporine levels remained in the normal range. Low MEGX values in the donors correlated with early evidence of cyclosporine toxicity (P < .0001), reduced graft function (bile output, P = .04; prothrombin time at day 5, P = .005), and prolonged stay in the intensive care (P = .022). The MEGX test is valuable and reflects the metabolic capacity of liver grafts. It can predict posttransplantation complications caused by cyclosporine toxicity, and further study would evaluate its incorporation into immunosuppressive protocols.
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PMID:Acute cyclosporine toxicity after liver transplantation is predicted by the lidocaine monoethylglycinexylidide test in the donor. 934 96

The purpose of this study was to evaluate the feasibility of developing multivariate equations that predicted blood pressure and measured levels of end-organ function indicators quantitatively up to 72 h in advance in critically ill patients with severe sepsis. Data collected prospectively from 59 patients entered into two sequential placebo-controlled clinical trials of recombinant interleukin-1 receptor antagonist in severe sepsis and septic shock was analyzed retrospectively. A series of multivariate equations were developed to predict systemic pressure, coagulation, and vital organ function indicators quantitatively at 24, 48, and 72 h after the onset of severe sepsis. These equations used physiologic and clinical laboratory measurements, plus circulating levels of eicosanoids and cytokines obtained when severe sepsis criteria first were met, and end-organ function indicators measured 24, 48, and 72 h later. Multivariate predictive equations were developed for temperature, white blood cell count, mean arterial pressure (MAP), Pao2/FiO2 ratio, the Murray acute lung injury score, alanine and aspartate aminotransferases, prothrombin time, partial thromboplastin time, platelet count, serum creatinine, and Glasgow Coma Scale. The percentage of data variation explained by the equations ranged from 11.4% (MAP at 48 h) to 85.1% (platelet count at 24 h). Linear regression analysis of predicted values, obtained by entering baseline data from individual patients into the multivariate equations, versus observed results at 24, 48, and 72 h yielded regression coefficients ranging from .371 (MAP at 48 h) to .924 (platelet count at 24 h). Among patients without end-organ dysfunction at baseline, sensitivities for predicting values consistent with the onset of organ failure were > or = 88% in 21/27 (78%) of the predictive equations. Resolution of organ failure indicators present at baseline was predicted successfully in individual patients, with 20/27 (74%) specificities > or = 76%. In critically ill patients with severe sepsis, multivariate analysis of interactions among clinical observations, standard laboratory tests, and inflammatory response mediators produced equations that predicted systemic blood pressure and inflammatory and end-organ function indicators quantitatively up to 72 h in advance. Whether or not this methodology might be developed further to predict subclinically the onset and resolution of acute organ failure and shock in critically ill patients, and if it can be validated in a prospective trial will require further studies.
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PMID:Multivariate regression modeling for the prediction of inflammation, systemic pressure, and end-organ function in severe sepsis. 937 72

Thirteen coagulation tests evaluating hemostatic and fibrinolytic indices and serum cytokine and plasma endotoxin concentrations were obtained in 34 foals with a positive sepsis score (septic group) and 46 age-matched healthy foals. Compared to healthy foals, the prothrombin, activated partial thromboplastin, and whole blood recalcification times were significantly longer in septic foals. The fibrinogen and fibrin degradation products concentrations, percent plasminogen, alpha-2 antiplasmin, and plasminogen activator inhibitor activities, and tumor necrosis factor and interleukin-6 activities were greater in septic foals. Protein C antigen and antithrombin III activity were significantly lower in septic foals. Blood cultures were positive for growth and endotoxin was detected in 19 of 29 and 15 of 30 septic foals, respectively. In septicemic foals with detectable endotoxin in the plasma, the prothrombin and activated partial thromboplastin times were significantly longer and the plasminogen and antithrombin III activities were significantly less than in septic foals in which endotoxin was not detected. Twenty-three of the 34 septic foals did not survive. Septic foals that did not survive were most likely to have a positive blood culture in which a gram-negative organism was isolated. Histopathologic evidence of hemorrhage was evident in 11 foals at postmortem examination and thrombosis was identified in 2 foals. The prothrombin time was significantly longer in foals that had multisite hemorrhage at postmortem examination. The results of this study indicate that clinically relevant alternations in hemostatic and fibrinolytic indices occur in neonatal foals with septicemia and that derangements can be correlated with the presence of endotoxin in plasma. Derangements in hemostatic or fibrinolytic indices were helpful in identification of septic foals with increased risk of coagulopathy, but were not helpful in predicting hemorrhage as compared to thrombus formation. Survival of septicemic foals was correlated with gram-negative bacteremia, but not with the presence of endotoxin or coagulopathy.
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PMID:Hemostatic and fibrinolytic indices in neonatal foals with presumed septicemia. 950 57

We have previously shown that an anticoagulant could attenuate inflammation in animal models of sepsis with disseminated intravascular coagulation (DIC) and that coagulation activation of human whole blood ex vivo results in a proinflammatory cytokine response. The current studies were performed to better understand mechanisms for the blood cell cytokine response and extend the investigation of such a response to endothelial cells as likely contributors to a vascular inflammatory response. Utilizing cell separation techniques, it was determined that the whole blood IL-8 response to coagulation activation or thrombin, specifically, was mediated by CD14+ monocytes. Moreover, thrombin was observed to stimulate both IL-8 and IL-6 production in cultured mononuclear cells. Analyses of the effects of coagulation activation and thrombin were extended to cultured human endothelial cells, and a similar cytokine response was observed. Thrombin catalytic activity appeared essential, since hirudin reduced thrombin-stimulated proinflammatory cytokine production in cultured monocytes and endothelial cells and prothrombin only weakly mimicked the thrombin response. The endothelial cell IL-8 and IL-6 response to thrombin could be mimicked by the thrombin receptor agonist peptide (TRAP), implicating a functional role of the classic thrombin receptor. Altogether, the results facilitate a better understanding of potential proinflammatory vascular responses to coagulation activation.
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PMID:Potential mechanisms for a proinflammatory vascular cytokine response to coagulation activation. 959 Feb 65

To determine the role of plasma tissue factor on disseminated intravascular coagulation (DIC) in trauma and septic patients, and also to investigate the relationships between tissue factor and various thrombin markers, we made a prospective cohort study. Forty trauma patients and 20 patients with sepsis were classified into subgroups according to the complication of DIC. Plasma tissue factor antigen concentration (tissue factor), prothrombin fragment F1+2 (PF1+2), thrombin antithrombin complex (TAT), fibrinopeptide A (FPA), and D-dimer were measured on the day of admission (day 0), and on days 1, 2, 3, and 4 after admission. The levels of plasma tissue factor in the DIC group were more elevated than those of the non-DIC group in both the trauma and the septic patients. In patients with sepsis, tissue factor levels on days 0 through 4 in the non-DIC group showed markedly higher values than those in the control patients (135 +/- 8 pg/ml). Significant correlations between tissue factor and PF1+2, TAT, FPA, and D-dimer were observed in the DIC patients, however, no such correlations were found in the non-DIC patients. These results suggest that elevated plasma tissue factor in patients with trauma and sepsis gives rise to thrombin generation, followed by intravascular coagulation.
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PMID:Significant correlations between tissue factor and thrombin markers in trauma and septic patients with disseminated intravascular coagulation. 965 33

We retrospectively determined the prevalence and nature of mortality as many as ninety days after 2736 primary and revision total hip arthroplasties performed in 2002 patients by one surgeon at a teaching hospital between January 1969 and December 1996. All but seventy-one of the patients had received prophylaxis against venous thromboembolic disease. There were no intraoperative deaths, and no events during the operation could be linked directly to postoperative mortality. Eight deaths (mortality rate, 0.3 per cent) occurred within ninety days after the 2736 procedures. Four deaths (mortality rate, 0.15 per cent) occurred during the initial hospitalization. The cause of seven of the deaths was determined. Three patients died as a result of preexisting disease (severe hepatorenal disease, metastatic esophageal cancer, or severe cardiac disease), and one patient died from sepsis with a gram-negative organism during a thoracotomy eight days postoperatively. A bleeding complication that occurred while the patient was receiving warfarin therapy led to the death of two other patients; one of these deaths occurred in 1974 and the other, in 1982. At the time that these patients were managed, the desired prothrombin time was considered to be twice the control value. The remaining patient, who had had a clip placed on the inferior vena cava after a pulmonary embolus occurred in 1970, died secondary to acute, severe thrombosis of this vessel after a total hip arthroplasty in 1971. The patient for whom the cause of death was not determined had had an artificial aortic valve and had been receiving chronic warfarin therapy. She died suddenly eighty-nine days postoperatively; no autopsy was performed. No patient died as the direct result of a known pulmonary embolus. No deaths related to venous thromboembolic disease or its prophylaxis or treatment occurred after 1982 (1458 operations). We attribute this, in part, to reduced levels of warfarin prophylaxis and improved management with warfarin. The ninety-day postoperative mortality rate after 2736 procedures performed over nearly three decades was low (0.3 per cent). This span of time included the period before the introduction of many current improvements in perioperative care, such as routine intubation of patients under general anesthesia, continuous monitoring of the electrocardiogram intraoperatively, and blood-gas determinations. When the patients who died as a result of known, severe preexisting disease were excluded, the mortality rate was 0.18 per cent (five of 2733).
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PMID:Postoperative mortality after total hip arthroplasty. An analysis of deaths after two thousand seven hundred and thirty-six procedures. 975 13

Antithrombin III (ATIII) and protein C (PC) are major inhibitors of the coagulation cascade and might regulate the cytokine network. We tested the possibility that a combined supplementation using these two inhibitors might have synergistic effects on sepsis-induced disseminated intravascular coagulation and shock. Hemodynamics, coagulation parameters, tumor necrosis factor (TNF) alpha, and interleukin 6 levels were measured in pigs submitted to a bolus infusion of Escherichia coli endotoxin (lipopolysaccharide). Four groups were studied: control lipopolysaccharide, ATIII (100 IU/kg), PC (50 IU/kg), and ATIII-PC (same doses). The endotoxin infusion resulted in a typical hypokinetic shock with disseminated intravascular coagulation in all animals. Compared with the control group, a significant improvement in mean arterial pressure and systemic vascular resistance was observed in the PC and ATIII-PC groups. The increase in lactate levels was almost completely blunted in the PC group. A significant lesser increase in TNFalpha levels was observed in the ATIII-PC group. No effects were seen on interleukin 6 levels. Coagulation and fibrinolysis parameters were not improved by ATIII and/or PC, except for a lesser decrease in prothrombin time in the ATIII-PC group. We conclude that in this acute endotoxic model, a combined supplementation using PC and ATIII concentrates has favorable effects on hemodynamic parameters and TNFalpha levels, independently from the anticoagulant actions of these inhibitors.
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PMID:Effects of a combined antithrombin III and protein C supplementation in porcine acute endotoxic shock. 984 Jun 53

To determine in vivo effects of interleukin (IL)-12 on host inflammatory mediator systems, 4 healthy chimpanzees received recombinant human IL-12 (1 microg/kg) by intravenous injection. IL-12 induced increases in plasma concentrations of IL-15, IL-18, and interferon-gamma (IFN-gamma), plus a marked antiinflammatory cytokine response (IL-10, soluble tumor necrosis factor [TNF] receptors, IL-1 receptor antagonist) and secretion of alpha-chemokines (IL-8, IFN-gamma-inducible protein 10) and beta-chemokines (monocyte chemoattractant protein-1, macrophage inflammatory protein-1beta). In addition, IL-12 elicited neutrophilic leukocytosis, neutrophil degranulation (elastase-alpha1-antitrypsin complexes), coagulation activation (F1 + 2 prothrombin fragment, thrombin-antithrombin III complexes), and fibrinolytic activation (tissue-type plasminogen activator, plasmin-alpha2-antiplasmin complexes). IL-12-induced activation of multiple host mediator systems was found only after 8-24 h, remained detectable until the end of the 48-h observation period, and occurred in the absence of detectable TNF and IL-1beta. These data may contribute to understanding the role of IL-12 in the pathogenesis of sepsis syndrome and the toxicity found after repeated injections of IL-12.
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PMID:Interleukin-12 induces sustained activation of multiple host inflammatory mediator systems in chimpanzees. 995 71

Disseminated intravascular coagulation (DIC) is a frequent complication of meningococcal sepsis in children. Despite the availability of potent antibiotics, mortality in meningococcal disease remains high (about 10%), rising to 40% in patients presenting in severe shock and consecutive DIC. As the clinical course and the severity of manifestations of systemic meningococcal infections varies there is a need for early diagnosis of the infection and of the stage of coagulopathy in order to reduce the high mortality rate. Few and rapidly available parameters are needed to classify the wide spectrum of clinical and laboratory findings in patients with DIC. The parameters include partial thromboplastin time, prothrombin time, plasma levels of fibrinogen, antithrombin III (AT III), fibrin monomers and D-dimer concentration, fibrin degradation products and the thrombocyte count. Monitoring the course of hemostasis findings in 28 pediatric patients (age between 3 months and 8 years, mean 3.1 years) with systemic meningococcal infections we observed a change of coagulation parameters already in the first stages of the infection: A prolongation of partial thromboplastin time mean 69.1 sec (range 22-150 sec, normal 30-45 sec), a decrease of prothrombin time to 45.7% (range 13-71%, normal 70-100%) and of AT III to an average level of 70% (normal 85-125%) was found 1 to 4 (-6) hours after admission. The following deterioration of prothrombin time and partial thromboplastin time turned out to be statistically significant (p < 0.05, signed rank test). The monitoring of hemostasis parameters mentioned above made it to possible define the stage of coagulopathy and thus to start a stage related therapy. Treatment consisted of shock control by liquid substitution, compensation of metabolic acidosis, correction of clotting disorders (AT III and heparin in case of pre-DIC; AT III and fresh frozen plasma in case of advanced DIC), antibiotic treatment (beta-lactam antibiotics e.g. cefotaxime or ceftriaxone), and--when necessary--catecholamine infusions. An early assessment of the coagulation disorders in meningococcal disease can be based on few coagulation parameters. Thus an appropriate treatment can be arranged in order to prevent a fatal outcome of meningococcal sepsis and to protect against the development of a Water-house-Friderichsen-syndrome.
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PMID:Diagnosis and stage-related treatment of disseminated intravascular coagulation in meningococcal infections. 1040 13


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