UMLS:C0036690 - FACTA Search

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Query: UMLS:C0036690 (sepsis)
59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty-two patients with hemoblastosis were examined in order to evaluate the possibility of using the criteria of the total system's inflammatory response syndrome (TSIRS) for the diagnosis of sepsis in hemoblastosis patients with leukopenia. The patients were examined before and after chemotherapy. Twelve patients with myelotoxic leukopenia developed TSIRS in response to a concomitant infection. No intensive care and resuscitation were needed in 9 of them; antibiotic therapy rapidly improved the clinical status. Three of these patients had to be transferred to intensive care wards. These patients differed from patients with TSIRS who needed no intensive care and from patients without TSIRS by higher fever (39.6 +/- 0.9, 39.1 +/- 0.4, and 36.5 +/- 0.7 degrees C, respectively), tachycardia (114.1 +/- 19.1, 105.3 +/- 12.8, and 84.0 +/- 10.0 stroke/min, respectively), thrombocytopenia (35.4 +/- 33.2.10(9), 55.1 +/- 34.5.10(9), and 89.2 +/- 95.1.10(9)/liter, respectively), prolongation of XIIa-dependent fibrinolysis (161.0 +/- 67.5. 64.7 +/- 57.0, and 46.2 +/- 45.8 min, respectively), decreased content of antithrombin III (79.6 +/- 8.1, 102.0 +/- 16.2, and 98.9 +/- 11.9%, respectively), and a more grave status according to the APACHEII score (20.4 +/- 5.2, 15 +/- 2.0, and 10.8 +/- 3.2, respectively). The APACHEII score and XIIa-dependent fibrinolysis were in direct correlation. We consider that the TSIRS/sepsis criteria are highly sensitive but not specific. They just permit singling out the group of patients part of whom may have sepsis.
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PMID:[Criteria of systemic inflammatory response syndrome are unacceptable in the diagnosis of sepsis in patients with leukopenia]. 1005 Mar 44

Sepsis is commonly associated with disturbances of the hemostatic balance. Most of the pathophysiological changes in sepsis are caused by endotoxin acting directly through endothelial injury or indirectly through release of cytokines with procoagulant effects. The relation between cytokines and hemostatic parameters was assessed in 32 patients with sepsis. Prothrombin fragment 1+2 (F1+2), thrombin-antithrombin III complexes (TAT), tissue type plasminogen activator (t-PA) functional and antigen, plasminogen activator inhibitor-1 (PAI-1), plasminalpha2-antiplasmin complexes (PAP), D-Dimer, thrombomodulin (TM) and von Willebrand factor (vWF) were measured in patients and in 30 healthy subjects. The levels of cytokines TNF-alpha and interleukin-6 (IL-6) also were determined. A significant increase of F1+2, TAT, PAI-1, PAP, and D-Dimer was observed in septic patients as compared with controls (p<0.0001), whereas t-PA activity was significantly reduced (p<0.01). The markers of endothelial cell activation TM, vWF, and t-PA antigen also were elevated significantly as compared with the control group (p<0.01). Finally, we found a marked increase of TNF-alpha and IL-6 (p<0.0001). Whereas the increase of cytokine levels could be partially responsible for the hemostatic activation, it did not correlate with markers of endothelial activation in patients with sepsis.
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PMID:Endothelial cell and hemostatic activation in relation to cytokines in patients with sepsis. 1023 Aug 94

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

Tissue factor pathway inhibitor (TFPI), the major downregulator of the procoagulant activity of tissue factor (TF), is synthesised by endothelial cells (EC) and acutely released in vitro after thrombin stimulation. Expression of TF on EC and subsequent thrombin generation occurs in vivo during sepsis or malignancy, inducing disseminated intravascular coagulation (DIC). The present study investigates the changes in plasma TFPI in relation to markers of in vivo thrombin generation induced by injection of factor Xa (FXa)/phospholipids in baboons at dosages leading to partial (48%) or complete fibrinogen depletion. The plasma concentrations of thrombin-antithrombin III (TAT) and fibrinopeptide A (FpA), as markers of in vivo generation of thrombin, were strongly enhanced after injection of FXa/phospholipids. TFPI levels, whether measured as antigen or activity, increased significantly in both treatment groups within few minutes, and were dependent on the dose of FXa/phospholipids. Significant positive correlations between plasma levels of TFPI and of TAT or FpA were observed. Altogether, our results indicate that experimentally induced in vivo generation of thrombin causes the acute release of TFPI, high-lighting a possible novel function of thrombin in downregulation of the coagulation process, potentially relevant for the outcome of DIC.
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PMID:Acute release of tissue factor pathway inhibitor after in vivo thrombin generation in baboons. 1061 51

Inter-alpha-inhibitor (IalphaI) is a human plasma serine proteinase inhibitor. It contains one light peptide chain called bikunin that exerts antiproteinase activity and other antiinflammatory functions. Bikunin is covalently linked to two heavy chains that, after tissular diffusion, stabilize the extracellular matrix. Owing to its negative acute-phase reactant character and its susceptibility to proteolysis, IalphaI has been implicated in the pathophysiology of sepsis. Moreover, IalphaI has been shown to exert a protective effect on a pig model of endotoxic shock. Twenty patients admitted to the intensive care unit (ICU) for a septic syndrome were included in the present study. IalphaI and antithrombin III (ATIII) levels were measured on admission. Sequential measurements of IalphaI could be done in 4 patients. We demonstrate that IalphaI levels are significantly decreased in plasma samples collected on admission from patients with sepsis (59 +/- 32 mg/L vs 241 +/- 70 mg/L; P < .0001). This decrease was greater in severe sepsis and septic shock than in sepsis. Death was not predictable from initiol IalphaI levels. In 2 patients with a favorable course, IalphaI values regularly increased during the ICU stay. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by immunoblot analysis and microsequencing, we characterized IalphaI-related components in plasma from several patients; they obviously arise from IalphaI through proteolytic cleavage. Thus, systemic proteolysis and decreased biosynthesis both contribute to the fall in the plasma level of IalphaI. Because IalphaI is very sensitive to proteolysis by polymorphonuclear granulocytes (PMNs) that are stimulated during sepsis, we suggest that IalphaI plasma level would be a useful marker for neutrophil proteinase activity. ATIII, as well as IalphaI, is considered a negative acute phase protein. Because in vitro ATIII is less susceptible than IalphaI to proteolysis by PMNs and because their relative levels weakly correlated, we suggest that an unspecific systemic proteolysis is not significantly involved in the ATIII deficiency occurring in sepsis.
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PMID:Inflammation-induced systemic proteolysis of inter-alpha-inhibitor in plasma from patients with sepsis. 1069 65

A retrospective study of 100 patients with disseminated intravascular coagulation from 1993 to 1997 is reported. Forty-five patients were neonates with a mean age of 12.6 days and 55 patients were infants, children and adolescents with a mean age of 6 years and 3 months. Most of them (91.5%) had complicated underlying conditions which included congenital anomalies, prematurity, malignancy, hematological and various diseases. Additionally, every patient had triggering conditions commonly identified as gram-negative septicemia. Bleeding and thromboembolic manifestations were found in 59.4 per cent and 19.8 per cent, respectively. The laboratory findings revealed red blood cell fragmentation, 89.6 per cent and thrombocytopenia, 85.8 per cent. Natural anticoagulants were studied in a few cases and revealed low levels of antithrombin III and protein C. The prompt effective management included treatment of underlying diseases, identification and relief of triggering conditions, correction of thrombocytopenia and coagulopathy, and fully supportive care. The overall case-fatality rate was 41.6 per cent which was not correlated with age, underlying diseases, triggering conditions, manifestation of bleeding, thromboembolism or shock, and exchange transfusion. However, a significant lower case-fatality rate was found in patients with positive culture (25%) as compared to those with sepsis and negative culture (51.7%) (p = 0.044). In addition, the febrile neutropenic patients, who showed good response to the administrated granulocyte-colony stimulating factor (G-CSF), survived from the DIC.
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PMID:Disseminated intravascular coagulation findings in 100 patients. 1073 May 20

Because thrombin has been implicated in sepsis, it has been proposed that antithrombin III (AT III) is beneficial due to its anticoagulatory and antiadhesive effects. Using intravital microscopy, we visualized leukocyte-endothelium interactions in postcapillary venules of the feline mesentery exposed to lipopolysaccharide (LPS). At a concentration of AT III that blocks leukocyte adhesion in postischemic mesentery, we found no role for thrombin in LPS-induced rolling, adhesion and emigration, or microvascular dysfunction. Furthermore, AT III did not attenuate leukocyte-endothelial interactions after tumor necrosis factor-alpha superfusion of the mesentery. In contrast, fucoidan, a selectin inhibitor, prevented almost all LPS-induced rolling and reduced adhesion, emigration, and microvascular dysfunction. In a model of endotoxemia, leukocyte recruitment into mesentery or lungs was unaffected by AT III. Finally, in a human cell system that mimics the flow conditions in vivo, human neutrophils rolled, adhered, and emigrated similar to the feline postcapillary microvessels, and AT III had no effect on leukocyte recruitment induced by LPS. If AT III has beneficial effects in endotoxemia, it is not due to a direct effect upon leukocyte rolling, adhesion, or emigration in postcapillary venules in vivo.
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PMID:Thrombin and leukocyte recruitment in endotoxemia. 1099 1

In sepsis, levels of the endogenous coagulation inhibitors antithrombin III and protein C are lowered as a result of complex formation with multiple activated clotting factors. In addition, their activity can further be curtailed by proteolytic inactivation. Loss of antithrombin III and protein C activity blocks the endogenous control mechanism for thrombin generation resulting in a state of systemic activation of coagulation and inflammatory processes. Levels of tissue factor pathway inhibitor, a third endogenous coagulation inhibitor, are increased in sepsis rather than decreased, probably reflecting a depletion of the endothelial cell bound tissue factor pathway inhibitor pool with loss of its endothelial protective function. Administration of any of these three inhibitors in various animal species and sepsis models reduces morbidity and mortality. In addition to their anticoagulant effects, these inhibitors also have various anti-inflammatory activities that may contribute to their protective effects. Phase II studies in patients with severe sepsis using coagulation inhibitors have indicated that this therapeutic approach may be useful. Large-scale phase III trials will ultimately decide whether adjunctive coagulation inhibitor replacement will have a place in the treatment of patients with severe sepsis.
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PMID:Coagulation inhibitor replacement in sepsis is a potentially useful clinical approach. 1100 2

Sepsis is a syndrome that is increasing in frequency and continues to be associated with an unacceptably high mortality. DIC is an important and common sequel of sepsis, is implicated in the development of multiple organ failure, and has been shown repeatedly to connote a poor prognosis. Increasing understanding of the pathogenesis of DIC has suggested several novel therapies designed to correct deficiencies in inhibitors of coagulation. To date, small randomized, controlled studies of antithrombin III concentrates in sepsis and DIC have shown a trend to increased survival, but have not achieved statistical significance. Currently, a large randomized controlled trial of antithrombin III in sepsis is being conducted. Until more data are available, important questions remain as to its proper place in the treatment of sepsis, septic shock, and DIC. Similarly, therapy with protein C and tissue factor-pathway inhibitor has been beneficial in animal models of sepsis and DIC. The results of controlled clinical trials in humans are eagerly awaited.
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PMID:Coagulation inhibitors in sepsis and disseminated intravascular coagulation. 1119 81

Sepsis and septic shock are the most frequent cause of mortality in non cardiologic intensive care units. Mortality of the severe form is still elevated in spite of the progress in the antibiotic therapy and in the hemodynamic and respiratory support. The most frequent cause of death is the Multi Organ Dysfunction Syndrome (MODS). The excessive inflammatory reaction and the damage of the microvascular bed secondary to the inflammation and to the disseminated intravascular coagulation (DIC) are important pathogenetic factors. In the sepsis a complex system of cellular activation initiates the release and the interaction of activators and inhibitors of the inflammation (cytokines), the activation of the enzymatic cascade systems (coagulation, fibrinolytic and complement systems) and the synthesis of proteases and anti proteases. The activation of the coagulation system, uncontrolled by the fibrinolytic system with formation of fibrin in the micro vascular bed, has an important role in the MODS. Experimental data and clinical observations suggest a possible therapeutic role of antithrombin III (AT) in sepsis; its plasma concentration is constantly decreased in patients with sepsis or septic shock and the entity of the decrease is correlated with the severity of the clinical picture and the outcome. At has a double function: regulation of the coagulation system and anti inflammatory properties. The anti inflammatory properties depend in part on the binding to the glycosaminoglycans of the endothelial cells and the consequent release of prostacyclin (PGI2). The anti inflammatory effect is independent from the anticoagulant one. The preliminary studies on the clinical use of AT were carried out in small groups of patients with DIC associated with pathologies of different etiology and often in very critical conditions. In general the evaluation criteria were the improvement or the normalization of the laboratory data. The interpretation of the therapeutic effect of AT is difficult because the dysomogeneity of these studies. The effect on mortality is controversial. Recently three prospective, randomized, double blind studies have been published in patients with severe sepsis and septic shock. The results of the single studies are inconclusive but the limited number of patients included in each study may explain the results. A meta-analysis of the data referring to the patients with severe sepsis and septic shock evidenced an odd ratio (OR) of 0.43 with 95% confidential interval of 0.20-0.92 (p = 0.029). The preliminary analysis of the results of a phase III study is unconclusive. Time, dosage and duration of treatment are still open to question. In perspective AT may be used in other clinical conditions associated with activation of the hemostatic system (cardiac surgery, stem cell transplantation, burns) even though the preliminary results must be confirmed by prospective studies. All these data suggest severe sepsis and septic shock as main criteria for treatment.
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PMID:[Antithrombin III concentrates in the treatmetn of sepsis and septic shock: indictions, limits and future prospects] . 1121 42

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