Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Optimal expectant management of preterm premature rupture of membranes (PROM) requires the early detection of chorioamnionitis. To date, however, no universally sensitive and specific marker for chorioamnionitis has been identified. Recently, the serial determination of plasma fibronectin, antithrombin, and prekallikrein has been reported to facilitate the early detection of sepsis in critically ill neonates and adult surgical patients. A cross-sectional study was undertaken to determine if plasma levels of these markers change significantly in patients with overt chorioamnionitis following expectant management of preterm PROM. Plasma levels of fibronectin and prekallikrein were not significantly different between the study (30 patients with overt chorioamnionitis following preterm PROM) and control (30 undelivered patients without antenatal complication matched for gestational age) groups. Antithrombin levels were significantly lower in the study group (p less than 0.05), but the magnitude of the difference (102% versus 94%) is not likely to be of clinical significance. We conclude that determination of plasma levels of fibronectin, prekallikrein, and antithrombin is not likely to aid in the early detection of chorioamnionitis in the setting of preterm (PROM).
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PMID:Evaluation of potential early markers of chorioamnionitis associated with preterm premature ruptured membranes. 229 8

Antithrombin (AT), prekallikrein (PK), and fibronectin (FN) were measured in the plasma of 400 patients with a variety of disease states seen at Detroit Receiving Hospital from October 1983 through June 1987. The average lowest AT measured in these 400 patients was 69 +/- 19 per cent (SD) (Normal = 75-120%). The average lowest AT level in 152 septic patients (50 +/- 17%) was significantly lower than in the 248 patients without sepsis (79 +/- 22%) (P less than 0.001). The average lowest PK levels measured in 132 patients was 52 +/- 19 (Normal = 80-120%). The average PK level in 64 septic patients (34 +/- 17%) was significantly lower than in 68 who were not septic (69 +/- 21%) (P less than 0.001). The average lowest FN levels measured in 109 patients was 230 +/- 118 mcg/ml (Normal = 200-350 mcg/ml). The average FN level in 47 septic patients (162 +/- 88 mcg/ml) was significantly lower than in the 62 nonseptic patients (285 +/- 138) mcg/ml. AT or PK levels less than 50 per cent or FN levels less than 150 mcg/ml during the first 24 to 48 hours after severe trauma or burns were associated with a development of later sepsis in 90 per cent, 77 per cent, and 70 per cent, respectively. Thus, low or falling levels of AT, PK, and FN may be of great help in predicting sepsis or providing an early diagnosis in critically ill or injured patients.
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PMID:Sepsis and antithrombin III, prekallikrein, and fibronectin levels in surgical patients. 274 28

Antithrombin (AT), prekallikrein (PK), and fibronectin (FN) levels were measured in the plasma of 290 patients. The mean (+/- SD) lowest AT level measured in 287 patients was 70% +/- 18% (normal, 75% to 120% of control). The mean lowest AT level in 81 septic patients (49% +/- 17%) was significantly lower than in the 206 patients without sepsis (78% +/- 22%). The mean AT level in 60 patients who died (42% +/- 22%) was significantly lower than in 227 patients who lived (78% +/- 19%). The mean lowest PK level measured in 71 patients was 42% +/- 17% (normal, 80% to 120%). The mean PK level in 32 septic patients (26% +/- 12%) was significantly lower than in 39 patients who were not septic (54% +/- 19%). The mean lowest FN level measured in 45 patients was 193 +/- 86 micrograms/mL (normal, 160 to 240 micrograms/mL). The mean FN level in 15 septic patients (128 +/- 72 micrograms/mL) was significantly lower than in the 30 nonseptic patients (266 +/- 84 micrograms/mL). Following AT, PK, and FN levels in critically ill surgical patients may allow earlier diagnosis and more effective treatment of sepsis.
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PMID:Antithrombin, prekallikrein, and fibronectin levels in surgical patients. 348 49

Antithrombin (AT) was measured in the plasma of 59 trauma patients at Detroit Receiving Hospital from July 1987 through December 1992 to determine how well low AT levels correlated with the outcome and development of later infections. The average lowest AT measured was 74 +/- 14% (SD) (normal = 75 to 120%). The mean lowest AT of the 11 trauma patients who developed sepsis (45 +/- 13%) was significantly lower than that of the 15 who developed an infection without sepsis (66 +/- 12%) (p < 0.001) and of the 33 who did not develop an infection (87 +/- 15%) (p <0.001). No patient with an AT always > or = 70% became septic or died, and no patient with an AT always > or = 90% developed an infection. In the 33 patients who did not develop infections, the mean AT levels rose progressively from 75 +/- 17% during the first 48 hours after admission to 91 +/- 11% during the next 48 hours. In contrast, the mean AT levels in the 26 patients who later developed infections were significantly lower (48 +/- 24%) during the first 48 hours and 60 +/- 16% during the next 48 hours (p < 0.016 and p <0.001). Of 10 patients with an AT < 60% in the first 96 hours, 9 (90%) developed an infection later. Low levels of AT, thus, may be of help in predicting infection, outcome, or both in severely injured patients.
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PMID:Antithrombin levels related to infections and outcome. 860 54

A prospective, randomized, controlled trial to examine the effects of antithrombin supplementation on mortality, coagulation and renal function has been carried out on 132 intensive care patients. Antithrombin activity was measured in all patients on admission to the intensive care unit (ICU). Patients with an antithrombin activity of less than 70% were randomized to either receive antithrombin replacement or to act as controls. Antithrombin activity was maintained above 70% in the treated patients throughout their stay on ICU. Ninety-three patients had an antithrombin activity of less than 70% and 35 received replacement therapy. Patients with antithrombin activity below 70% remained on the ICU significantly longer and had a significantly higher mortality rate than patients with antithrombin activity above 70%. Antithrombin supplementation neither reduced mortality nor shortened the intensive care stay. Fifty patients with reduced antithrombin activity remained on the ICU for at least 4 days, 25 received antithrombin and 25 acted as controls; coagulation parameters and renal function have been monitored in these patients. Fibrinogen concentration and platelet count were unaffected by antithrombin replacement. Antithrombin supplementation did not appear to reduce the incidence of impaired renal function in sepsis, trauma and postoperative patients. The creatinine clearance fell below 20 ml/min in eight patients in the no-treatment arm while by comparison only three patients in the treatment arm developed impaired renal function. Our study does not demonstrate a clear role for the use of antithrombin supplementation in intensive care, however the finding that antithrombin reduced renal impairment is encouraging and a larger study to confirm this finding is at present underway.
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PMID:A pilot study of antithrombin replacement in intensive care management: the effects on mortality, coagulation and renal function. 925 38

Antithrombin (AT) is a single-chain glycoprotein in plasma and belongs to the family of the serpins. It is synthesized in liver parenchymal cells, and its plasma concentration is between 112-140 mg/L. AT is a unique inhibitor of the clotting system and neutralizes most of the enzymes generated during activation of the clotting cascade, especially thrombin, factors Xa and IXa. Equimolar, irreversible complexes are formed between AT and the enzymes. The interaction between AT and the activated clotting factors is at least 1,000-fold increased in the presence of heparins. Heparins bind to multiple sites of the AT molecule resulting in a steric reconfiguration. Heparins contain a specific pentasaccharide unit which is the minimum requirement for AT binding. The glycosaminoglycan (GAG) heparan sulfate found on endothelial cell surfaces also contains this pentasaccharide and can thus "activate" AT. It is believed that much of the physiological inactivation of enzymes by AT occurs on the endothelium, mediated by heparan sulfate. The binding of AT to the GAGs also releases prostacyclin which possesses strong antiinflammatory properties. Deficiencies of AT are inherited or acquired. Only acquired defects due to increased consumption are discussed, most notably AT in DIC, especially DIC in sepsis. During acute DIC, clotting factors and inhibitors are consumed faster than they can be reproduced. This consumption of AT is of great significance in DIC and sepsis, and plasma AT levels predict outcome. AT levels drop early in sepsis and laboratory signs of DIC can already be found in patients with SIRS and early sepsis. The important role of AT in DIC and sepsis is the basis for considering antithrombin concentrates as an additional therapeutic modality.
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PMID:Antithrombin: its physiological importance and role in DIC. 951 76

Replacement of antithrombin has proved to be effective for treating disseminated intravascular coagulation. The administration of antithrombin is also useful for preventing organ failure in animals challenged with endotoxin or bacteria, and it increases the survival rate of such animals. Since inhibition of coagulation abnormalities by heparin failed to prevent organ failure in animals challenged with bacteria, antithrombin might exert therapeutic effects independently of its anticoagulant effect. These therapeutic mechanisms of antithrombin have been explored by using animal models of septicemia. Antithrombin prevents pulmonary vascular injury by inhibiting leukocyte activation in rats challenged with endotoxin. A higher dose of antithrombin was required to prevent pulmonary vascular injury than was required to inhibit disseminated intravascular coagulation. This preventive effect of antithrombin is mediated by the promotion of endothelial release of prostacyclin, an inhibitor of leukocyte activation. An interaction between antithrombin and heparin-like glycosaminoglycans on the endothelial cell surface appears to be important for this effect. Heparin inhibits such therapeutic effects of antithrombin by preventing it from interacting with the cell surface heparin-like glycosaminoglycans. Since activated leukocytes are of critical importance in patients with sepsis-associated organ failure, this anti-inflammatory activity of antithrombin may explain why it can prevent organ failure as well as coagulation abnormalities in patients with sepsis.
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PMID:Antithrombin prevents endotoxin-induced pulmonary vascular injury by inhibiting leukocyte activation. 966 67

Antithrombin (AT) is an important inhibitor of the coagulation system, acting at many different levels of the coagulation cascade. This inhibitory action is enhanced several-fold by the glycosaminoglycan heparin. AT deficiency can be encountered in hereditary disorders, which are rare, or in acquired conditions, in which there is an excessive consumption of AT. Acquired AT deficiency is a common condition in sepsis, after major trauma or surgery, with or without associated disseminated intravascular coagulation (DIC). In these conditions, low levels of AT have been correlated with a poor outcome due to the development of multiple organ failure. Although supplementation with AT has been shown to attenuate the extent of organ failure in critically ill patients, it has not been possible to significantly improve the survival of these patients by administration of AT. An interesting new approach to AT treatment is based on the hypothesis that AT has specific effects that are independent of the coagulation cascade. Data from cell culture and animal experiments have demonstrated that AT can promote the endothelial production of prostacyclin and may therefore have anti-inflammatory actions. This effect is based on the interaction of AT with glycosaminoglycans in the cell membrane, and is independent of heparin. The role of AT in vessel wall antithrombogenicity is being increasingly appreciated. The concept of neointimal hyperplasia following vascular injury involves thrombin as an important mediator and thus, in addition to the anti-inflammatory effects of AT, new horizons in which AT may have an important role in the prevention of post-traumatic hyperplastic response are also evolving.
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PMID:Antithrombin: facts and new hypotheses. 1010 92

Antithrombin (AT) is the most important inhibitor of the coagulation system. Due to the high cost of AT treatment, there must be rational arguments to justify its use. Established indications for AT substitution include hereditary homozygous AT deficiency in newborn babies and hereditary AT deficiency before or during certain situations, for example, surgery and pregnancy. AT substitution therapy can also be justified in the treatment of complex coagulation disorders, sepsis with disseminated intravascular coagulation and acute thromboembolic events with reduced AT activity. Administration of AT concentrates to patients with nephrotic syndrome or stable hepatopathy is not justified. To achieve an anti-inflammatory effect in patients with sepsis, it is thought that above-normal levels of AT activity (> 140% of the normal level) are probably needed. Although currently available data on the effect of AT in the treatment of sepsis are insufficient, results from controlled studies will soon become available and will show whether sepsis is an indication for AT substitution.
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PMID:Antithrombin substitution therapy. 1010 95

Sepsis is a frequent complication of critically ill patients and its incidence is increasing. Currently, septic shock is the most common cause of death in non-coronary intensive care units. Over the last 10 to 15 years, new antibiotics and increasingly sophisticated critical care have had little impact on the mortality rate of septic shock. The Italian SEPSIS Study, carried out in 99 intensive care units in 1994, reported mortality rates of 52% and 82% for severe sepsis and septic shock respectively. New therapeutic approaches aimed at neutralizing microbial toxins and modulating host mediators have shown some efficacy in large clinical trials and/or in animal models, but to date, no therapy of sepsis aimed at reversing the effects of bacterial toxins or of harmful endogenous mediators of inflammation has gained widespread clinical acceptance. Because of the strong association of severe sepsis with a state of activation of blood coagulation and of the potential role of capillary thrombosis in the development of the multiple organ dysfunction syndrome, anticoagulant agents have been tested in the setting of septic shock. However, neither administration of heparin nor of active site-blocked factor Xa or of anti-tissue factor antibodies have proven effective in preventing deaths due to septic shock in animal models. In contrast, infusion of antithrombin, protein C, or tissue factor pathway inhibitor all resulted in a significant survival advantage in animals receiving lethal doses of E. Coli. Antithrombin concentrates have been used in a significant number of critically ill patients. A double-blind, placebo controlled study carried out in 3 italian intensive care units has recently shown that the administration of antithrombin aimed to normalize plasma antithrombin activity had a net beneficial effect on 30-day survival of patients requiring respiratory and/or hemodynamic support because of severe sepsis and/or post-surgery complications.
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PMID:Antithrombin replacement in patients with sepsis and septic shock. 1032 25


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