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)

Plasma levels of thrombin-antithrombin III complex (TAT), plasmin-alpha 2-plasmin inhibitor complex (PIC) and active plasminogen activator inhibitor (PAI) were assayed in 66 cases of disseminated intravascular coagulation (DIC). Significant elevation of both TAT and PIC was observed in all cases of DIC. Most elevated levels of TAT were seen in DIC with acute promyelocytic leukaemia (APL) and sepsis. The highest levels of PIC were seen in DIC with APL but were much lower in sepsis. A significant elevation in active PAI was observed in DIC due to acute leukaemia (apart from APL), chronic myeloid leukaemia and sepsis, but not in APL, non-Hodgkin lymphoma and cancer. Active PAI was higher in patients with multiple organ failure (MOF) than in those without MOF while PIC was lower in patients with this complication. Thus, the balance of coagulation and fibrinolysis varied according to the underlying cause of DIC; APL had more dominant activation of fibrinolysis, while sepsis had greater activation of coagulation. It is suggested that the inhibition of secondary fibrinolytic activation plays an important role in the progression of MOF by the disturbance of the microcirculation.
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PMID:Study of the balance between coagulation and fibrinolysis in disseminated intravascular coagulation using molecular markers. 786 91

This study explored the relationship between cytokines (TNF, IL-1, IL-6), coagulation and fibrinolytic factors in the early stage of sepsis syndrome and the relation between these factors with the severity of inflammatory illness as measured by the Simplified Acute Physiology Score (SAPS). Twenty-one normal controls were compared to 34 patients divided into three categories ranging from uncomplicated postoperative patients, to patients with severe infectious conditions including septic shock. A major hemostatic imbalance was demonstrated with particularly marked reduction in fibrinolytic activity [drop of antithrombin III (ATIII) and protein C with an increase of plasminogen activator inhibitor (PAI-1) levels] which were directly correlated with the severity of the inflammatory state. Both ATIII and PAI-1 levels were correlated with the levels of TNF and IL-6 and the severity of illness as measured by SAPS. We established an index, ATIII/PAI-1 antigen that is significantly different among the four groups (p < 0.001) and strongly correlated with the SAPS (p < 0.001). As PAI-1 could be secreted not only by TNF activating endothelial cells but also by hepatocytes activated by insulinemia, treatment of sepsis with cytokine-specific agents might be of limited effect.
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PMID:Coagulation/fibrinolysis balance in septic shock related to cytokines and clinical state. 795 54

We measured various coagulable factors and molecular markers in plasma and serum in the disease group including DIC, DIC suspect, thrombosis, acute myocardial infarction, angina pectoris, sepsis, malignant tumor and type II diabetes and the healthy subject group, and surmised the intravascular coagulative-fibrinolytic activity in each disease group compared with the healthy group. Additionally we selected parameters useful for early detection of the pre-thrombotic state and hypercoagulable state. As a result, of the parameters for the coagulative system, those considered useful were the assay of soluble fibrin monomer complexes using the synthetic substrate (FM.Oita), assay of soluble fibrin monomer complexes using HPLC(SFMC.Oita) and thrombin-anti-thrombin III complex (TAT) in this order. Of the parameters for the fibrinolytic system, those considered useful were FDP assay using ELISA (FDP.Oita) and plasmin-alpha 2 plasmin inhibitor complex (PIC). This FDP.Oita had a considerably high detection sensitivity compared with the FDP assay (Diayatron Co.) using the latex photometric immunoassay which has been commercially available. When measurement was made with plasma and serum in the subject disease group as the sample by the high sensitivity assays mentioned above, it was made clear that both the coagulative activity and fibrinolytic activity are increased, albeit with some differences in intensity, in all the disease groups compared with the healthy group. In order for the hypercoagulable state and pre-thrombotic state to be detected, it is important to know the balance between the coagulative activity and fibrinolytic activity. According to the results of the present experiment, a significant directly proportional correlation was recognized between FM.Oita and FDP.Oita and between TAT and FDP.Oita. Therefore, examination of these ratios will be a more detailed indicator of coagulative-fibrinolytic activity than the TAT/PIC ratio, PAI-1/TPA ratio and ATIII/alpha 2 PI ratio hitherto in use. If useful molecular markers such as FM.Oita are measured over time in various cases and these data are compiled and analyzed statistically, it will not be long before the criteria for the hypercoagulable state and pre-thrombotic state are established.
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PMID:[Molecular marker for detecting hypercoagulable state]. 810 79

The clinical relevance of determination of plasma antithrombin III(ATIII) and alpha 2-plasmin inhibitor (alpha 2 PI) activities in patients with disseminated intravascular coagulation (DIC) was analyzed. Although the plasma ATIII activity was decreased in patients with DIC, no significant correlation was observed between plasma level of ATIII and that of thrombin-antithrombin III complex or prothrombin fragment 1+2. The extent of the decrease of ATIII in DIC was the most marked in cases associated with septicemia. The plasma level of ATIII in septicemia without DIC was significantly lower than that in DIC cases without septicemia, suggesting that the decrease of ATIII level could not be related to the pathophysiology of DIC, but to that of septicemia. The plasma half-life of ATIII in septicemia without DIC was significantly shortened in the absence of the increase of TAT level, suggesting that the extravasation of ATIII might be induced probably due to the endothelial damage in septicemia. The alpha 2-Plasmin inhibitor level was decreased in DIC patients. The decrease was the most marked (lower than 60% of normal) in patients with excessive fibrinolysis in which fibrinogen degradation was induced. The plasma level of alpha 2PI was significantly higher in the DIC cases with septicemia than in those without septicemia. The ATIII/alpha 2PI ratio was significantly lower in DIC cases with septicemia than in those with solid tumor or acute leukemia. Moreover, the ATIII/alpha 2PI ratio was significantly lower in MOF cases than in non-MOF cases in septicemia. The mortality of the MOF cases did not correlate with the ATIII/alpha 2PI ratio, but with the plasma level of PAI-1, suggesting that the decrease of ATIII/alpha 2PI ratio might not reflect the irreversible endothelial cell damage. Based on these observations, the calculation of ATIII/alpha 2PI in DIC patients would provide the following information; (1) a low ATIII/alpha 2PI ratio (less than 0.6) was frequently observed in septicemia, which could be related to the occurrence of organ dysfunction; (2) a high ATIII/alpha 2PI ratio (higher than 1.0) with the marked decrease of alpha 2PI level (lower than 60% of normal) suggests the occurrence of excessive fibrinolysis in which anti-fibrinolytic therapy should be considered when clinical bleeding was present; (3) The ATIII/alpha 2PI ratio near 1.0 was observed in DIC associated with the pathological conditions other than described above, such as solid tumors, in which the coagulation and fibrinolysis was almost equally activated.
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PMID:[Clinical relevance of determination of plasma ATIII and alpha 2 PI activities in patients with DIC--application of the molecular markers for the analysis of pathophysiology of DIC]. 810 83

The role of interleukin 6 (IL-6) in the toxic sequelae of sepsis is controversial. To assess the part of IL-6 in inflammatory responses to endotoxin, we investigated eight chimpanzees after either a bolus intravenous injection of Escherichia coli endotoxin (n = 4; 4 ng/kg) or after the same dose of endotoxin with a simultaneous bolus intravenous injection of an anti-IL-6 mAb (30 mg; n = 4). Anti-IL-6 did not affect the induction of the cytokine network (tumor necrosis factor [TNF], soluble TNF receptors types I and II, and IL-8) by endotoxin, nor did it influence the occurrence of a neutrophilic leukocytosis and neutrophil degranulation, as monitored by the measurement of elastase-alpha 1-antitrypsin complexes. In contrast, anti-IL-6 markedly attenuated endotoxin-induced activation of coagulation, monitored with the plasma levels of the prothrombin fragment F1+2 and thrombin-antithrombin III complexes, whereas activation of fibrinolysis, determined with the plasma concentrations of plasmin-alpha 2-antiplasmin complexes, remained unaltered. We conclude that IL-6 does not have a feedback effect on the release of other cytokines after injection of endotoxin, and that it is not involved in endotoxin-induced neutrophilia or neutrophil degranulation. IL-6 is, however, an important intermediate factor in activation of coagulation in low grade endotoxemia in chimpanzees.
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PMID:Elimination of interleukin 6 attenuates coagulation activation in experimental endotoxemia in chimpanzees. 814 42

Sepsis is due to its lethality, which varies round 25%, one of the major problems of contemporary clinical medicine. Classical therapeutic approaches, i.e. chemotherapy, surgical elimination of foci and intensive therapy focused on maintenance of vital functions have obviously reached the limit of effectiveness beyond which they are unable to advance any further. Therefore great efforts are devoted to research into pathogenetic mechanisms involved in sepsis with the aim to use their effect to improve therapeutic results. In the submitted paper the authors analyze the definition of sepsis, explain the concept of the syndrome of systemic inflammatory response and summarize the contemporary state of knowledge of the pathogenesis. A review of structures and mechanisms involved in the genesis and development of sepsis (complement, factor XII, macrophage, endothelial cell, polymorphonuclear leucocyte, thrombocyte etc.) is supplemented by a list of substances which act as mediators of inflammations. The conclusions for practice summarize contemporary therapeutic possibilities, i.e. classical means as well as more recent approaches (colony stimulating factors, haemodiafiltration, antithrombin III, monoclonal antibody against endotoxin). The authors review briefly therapeutic means which are developed at present and which should make it possible to interfere actively with the pathogenesis of the disease.
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PMID:[Contemporary views on the problem of sepsis]. 816 68

Circulating proteolytic activity (PA) increases following burn or surgical trauma. Challenging traumatized mice with the yeast Candida albicans further increases PA. Once a PA threshold has been passed, mortality increases as PA increases. The purposes of this study were to determine (i) if gram-negative bacterial challenge affects circulating PA and mortality as Candida challenge does and (ii) if proteinase inhibitor treatment with aprotinin, antithrombin III, and alpha 1-proteinase inhibitor decreases circulating PA and increases the survival of burned mice infected with a bacterium. For all bacteria tested (Proteus mirabilis, Pseudomonas aeruginosa, and Klebsiella pneumoniae), burn plus challenge significantly elevated PA and mortality above levels in mice that were only burned or only challenged. Quantitative culture counts indicated that the mice died of sepsis. Proteinase inhibitor treatment of mice burned and challenged with K. pneumoniae significantly decreased circulating PA, decreased the hepatic microbial load, and increased survival. Hence, in traumatized mice challenged with either C. albicans or gram-negative bacteria, a relationship exists between proteolytic load and subsequent septic death. Parallels between these animal studies and human studies are discussed.
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PMID:Proteolytic activity and fatal gram-negative sepsis in burned mice: effect of exogenous proteinase inhibition. 818 36

Whole-blood chemiluminescence and levels of leukocyte proteases and plasma protease inhibitors were studied in 43 patients with acute, generalized peritonitis. An almost three-fold increase in whole-blood chemiluminescence was found in acute peritonitis, which may indicate activation or "priming" of the leukocytes by blood-borne factors. High levels of leukocyte elastase and neutrophil proteinase 4(3) were found in plasma and peritoneal exudate. Patients with sepsis had higher plasma levels of both proteases than other patients. Large variations in the plasma levels among patients decreased their sensitivity as markers of infectious complications during the postoperative period. The plasma levels of the protease inhibitors followed three different patterns of reaction. The acute phase proteins alpha 1-proteinase inhibitor and C1-inactivator, increased during the first week of disease, to normalise later in its course. alpha 2-macroglobulin, antithrombin III and alpha 2-antiplasmin were all decreased from onset and normalised later in the course, while secretory leukocyte protease inhibitor showed a slow decrease throughout the course of disease. In peritonitis exudate, the levels of the main protease inhibitors, alpha 1-Proteinase Inhibitor and alpha 2-Macroglobulin, were decreased, probably due to complexation and subsequent elimination, as a part of the defense against liberated leukocyte proteases. The immunoreactive and especially functional levels of the protease inhibitors alpha 2-Antiplasmin, Antithrombin III and C1-Inactivator were also decreased in the exudate, indicating an increased turn-over of these proteins through activation of the cascade systems and/or break-down by leukocyte proteases. In contrast to the other inhibitors, secretory leukocyte protease inhibitor showed higher levels in exudate than in plasma, and unexpectedly high exudate/plasma-quotients were seen in cases with colonic perforations. Degradation of complement factor 3 (C3) and decreased "opsonic capacity" were found in exudate. The "opsonic capacity" could be correlated to the levels of leukocyte proteases in the exudate, which indicates that degradation of complement factor 3 may have been at least partly due to the action of leukocyte proteases. Further depletion of complement factors in exudates of long-standing peritonitis or abscesses may create a vicious circle of deficient opsonisation and clearance of bacteria, as earlier reported for chronic pleural exudates.
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PMID:Protease-antiprotease levels and whole-blood chemiluminescence in acute peritonitis. 822 20

The proband, a 43-year-old woman, suffered from right transverse sinus thrombosis during oral contraceptive treatment. A month after stopping the drug, her plasma activities of antithrombin III, protein C, protein S, heparin cofactor II, plasminogen and plasminogen activator inhibitor were normal, but her plasma histidine-rich glycoprotein (HRG) level was only 21% of the normal level of 109.5 +/- 51.5% (mean +/- 2 SD). The HRG concentrations in her plasma determined on four different occasions over 6 months were similar. She showed no clinical signs of liver insufficiency or sepsis. Low levels of plasma HRG (20% to 35% of normal) were also found in her aunt, uncle and two daughters. These results suggest that congenital HRG deficiency is inheritary in this family.
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PMID:Congenital histidine-rich glycoprotein deficiency. 823 32

Tumor necrosis factor (TNF) is considered to be a pivotal mediator of endotoxin-induced lethality. To assess the intermediate role of TNF in specific systemic inflammatory responses known to contribute to tissue injury in endotoxemia, eight healthy adult chimpanzees were intravenously injected with Escherichia coli endotoxin (4 ng/kg). In four of these animals the administration of endotoxin was followed immediately by a bolus intravenous injection of an anti-TNF monoclonal antibody (15 mg/kg). Treatment with anti-TNF completely prevented the endotoxin-induced increase in serum TNF activity, and profoundly reduced the appearance of interleukin-6 and -8 (both P < .05). Neutrophilia and lymphopenia were not affected by anti-TNF, whereas neutrophil degranulation, as measured by the plasma concentrations of elastase-alpha 1-antitrypsin complexes, was only slightly reduced (peak levels after endotoxin alone 31.0 +/- 3.4 ng/mL, versus 25.5 +/- 3.4 ng/mL after endotoxin with anti-TNF; P < .05). Anti-TNF did not influence endotoxin-induced activation of the coagulation system, as reflected by unchanged increases in the plasma concentrations of the prothrombin fragment F1 + 2 and thrombin-antithrombin III complexes. In contrast, anti-TNF strongly attenuated the activation of the fibrinolytic system, ie, peak plasma levels of plasmin-alpha 2-antiplasmin were 33.8 +/- 11.1 nmol/L after endotoxin alone and 17.0 +/- 2.9 nmol/L after endotoxin with anti-TNF (P < .05). These results suggest that TNF is not the common mediator of systemic inflammatory changes in low-grade endotoxemia. Moreover, the finding that in this mild model anti-TNF specifically inhibited fibrinolysis suggests that treatment with anti-TNF potentially may enhance the tendency towards microvascular thrombosis in sepsis.
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PMID:Differential effects of anti-tumor necrosis factor monoclonal antibodies on systemic inflammatory responses in experimental endotoxemia in chimpanzees. 828 42

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