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

The endothelium plays an important role in the regulation of haemostasis by producing substances such as thrombomodulin (TM). The influence of long-term volume replacement with different types of fluid on the TM-protein C-protein S system was investigated in a prospective, randomized study. Thirty trauma patients and 30 patients suffering from sepsis after major surgery received either 10% low-molecular weight (LMW) hydroxyethylstarch solution (HES-trauma, n = 15; HES-sepsis, n = 15) or 20% human albumin (HA-trauma, n = 15; HA-sepsis, n = 15) for 5 days to maintain central venous pressure (CVP) between 12 and 16 mm Hg. Plasma concentrations of TM, protein C, (free) protein S and thrombin-antithrombin (TAT) were measured in arterial blood samples obtained on the day of admission to the intensive care unit or on the day of diagnosis of sepsis and over the next 5 days. There were no differences between HA- and HES-treated trauma patients. Protein C and protein S also did not differ between HA- and HES-treatments. At baseline, TM plasma concentrations were increased to > 40 micrograms litre-1 in both sepsis groups only. In the HA-sepsis group, TM increased significantly (from 48.1 (SD 13.9) to 68.4 (13.0) micrograms litre-1), whereas it remained almost unchanged in the HES-sepsis group. In HES-sepsis patients, protein C (from 51.0 (10.1) to 71.9 (8.9)%) and protein S (from 19.0 (6.0) to 40.8 (11.4)%) increased significantly during the study, whereas both remained reduced in HA-patients. TAT (indicating intravascular coagulation) did not differ between the two fluid groups. We conclude that in trauma patients, the type of volume therapy had no influence on the TM-protein C-protein S system. In sepsis patients, volume therapy with HES was beneficial, whereas infusion of HA had no substantial positive effect on endothelial-associated coagulation.
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PMID:Does the type of volume therapy influence endothelial-related coagulation in the critically ill? 3286 9

We studied the influence of age on mortality and severity of clotting abnormalities in 79 children (median age: 3.1 years) with meningococcal sepsis. Parameters of coagulation and fibrinolysis and plasma levels of cytokines were prospectively measured on admission. The mortality rate was 27%. The age of survivors was significantly different from that of non-survivors (p = 0.013). With the exception of FVII, vWF and t-PA, parameters of coagulation and fibrinolysis, as well as plasma cytokine levels were related to outcome. Patients were divided in two groups: younger and older than median age. The mortality in children < or = 3.1 years was 40% versus 13% in children > 3.1 years (p = 0.006). In contrast to cytokine levels, which were not different between the two age groups, fibrinogen, prothrombin, factors V, VII, VIII, vWF, protein C, antithrombin, FDP, and the ratio PA1-1/t-PA were related to age, indicating a more severe coagulopathy in children < or = 3.1 years despite a similar degree of inflammatory response. A relative deficiency of coagulation factors due to an immature state of the clotting system, as well as an inadequate fibrinolytic response, both related to age may have caused this more severe coagulative response in younger children, and may have contributed to the higher mortality rate.
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PMID:Age-related differences in outcome and severity of DIC in children with septic shock and purpura. 897 13

Isolated acquired factor VII deficiency is uncommon. We report 11 cases of acquired factor VII deficiency associated with severe systemic sepsis. All patients initially displayed a heterozygous-like factor VII deficiency confirmed by both clotting and amidolytic assays, associated with low factor VII antigen levels, and increased haemostasis markers (D-dimers, prothrombin fragments 1.2, thrombin-antithrombin complexes). After sepsis recovery, normal factor VII levels were evidenced. Isolated factor VII consumption or proteolytic degradation by leucocyte proteases can be evoked, but the mechanism of acquired factor VII deficiency during sepsis remains to be elucidated. The knowledge of this syndrome should avoid false diagnosis of congenital factor VII deficiency.
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PMID:Acquired isolated factor VII deficiency during sepsis. 921 52

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

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

Patients with sepsis or after major surgery have decreased plasma levels of the anticoagulant protein antithrombin. In such patients elevated levels of interleukin-6 (IL-6) are present and this interleukin is known to induce positive and negative acute phase responses. To investigate the possibility that antithrombin acts as a negative acute phase response-protein we performed studies on the human hepatoma cell line HepG2 in vitro and baboons in vivo. HepG2 cells were treated with recombinant human IL-6, IL-1beta, or combinations of the latter two, and tested for production of antithrombin, fibrinogen and prealbumin (transthyretin). This treatment resulted in a dose dependent increase in fibrinogen concentration (with a maximum effect of 2.8-2.9-fold) and a dose dependent decrease in prealbumin (with a maximum effect of 0.6-0.7-fold) and antithrombin concentrations (with a maximum effect of 0.6-0.8-fold). Simultaneous treatment of the HepG2 cells with IL-6 (1,000 pg/ml or 2,500 pg/ml) and IL-1beta (25 pg/ml), provided more extensively decreased prealbumin (0.8 and 0.6-fold, respectively) and antithrombin concentration (0.7 and 0.6-fold, respectively) compared to the single interleukin treatment at these concentrations. Baboons treated with 2 microg IL-6 x kg body-weight(-1) x day(-1) showed increased plasma CRP levels (59-fold, p <0.05) and decreased prealbumin (0.9-fold, p <0.05) and antithrombin (0.8-fold, p <0.05) plasma levels, without evidence for coagulation activation. Our results indicate that antithrombin acts as a negative acute phase protein, which may contribute to the decreased antithrombin plasma levels observed after major surgery or in sepsis.
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PMID:Antithrombin acts as a negative acute phase protein as established with studies on HepG2 cells and in baboons. 930 58

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

In patients with sepsis and septic shock, both coagulation and fibrinolysis are activated frequently leading to the syndrome of diffuse intravascular coagulation (DIC). The different mechanisms leading to abnormalities in coagulation and fibrinolysis are discussed in detail. The coagulation and fibrinolytic system appear to be influenced by the septic process largely independently, leading to a procoagulant imbalance between these systems. Coagulation is initiated by mediator-induced expression of tissue factor and is associated with consumption of the natural coagulation inhibitors antithrombin III, protein C, and protein S. As a result, high plasma levels of thrombin-antithrombin complex (TAT) can be found. The effects on fibrinolysis are dominated by (highly) increased levels of plasminogen activator inhibitor type 1 (PAI-1), leading to inadequate fibrinolysis. Although levels of plasminogen activator antigen are increased, its activity is almost completely inhibited by PAI-1. The resulting effects predispose to a procoagulant state, with widespread fibrin deposition, which may be an important mechanism contributing to multiple organ failure. A thorough understanding of the pathophysiological mechanisms underlying the DIC-syndrome is a prerequisite for a rational approach and future therapy for this severe complication of sepsis.
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PMID:Derangements of coagulation and fibrinolysis in critically ill patients with sepsis and septic shock. 951 78

Sepsis and its associated complications of disseminated intravascular coagulation (DIC) and multiple organ dysfunction syndrome (MODS) continue to be a major cause of morbidity and mortality. Improved detection of all forms of DIC is essential to assure earlier diagnosis. Studies already indicate that the therapeutic use of antithrombin (AT) concentrate may produce a more positive outcome for sepsis-associated DIC. If DIC could be identified earlier and AT concentrate could then be given earlier in the sepsis continuum, study results for the use of AT concentrate in humans might reveal a statistically significant difference versus placebo, and the efficacy of AT concentrate for this syndrome is more likely to be proved. Fixed-bolus doses of AT concentrate based on body weight are currently preferred, but improved, user-friendly assays for plasma AT levels would permit more rapid turnaround time for AT results and could help fine-tune the use of AT concentrate to the specific needs of each patient. Clinical trials involving the therapeutic use of AT concentrate in sepsis should continue, and it can be hoped that their design will reflect the concepts and conclusions offered by this panel of investigators.
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PMID:Therapeutic use of antithrombin concentrate in sepsis. 957 41

We previously demonstrated that antithrombin III reduced the injury to endothelial cells caused by activated leukocytes in rats administered endotoxin. This occurred via the increase of the endothelial release of prostaglandin I2, which is a potent inhibitor of leukocyte activation. We evaluated the dose of antithrombin III required to prevent such endothelial cell injury in rats administered endotoxin, by comparing the effects of various antithrombin II doses on the pulmonary vascular injury. The intravenous administration of endotoxin, 5 mg/kg, produced a transient accumulation of leukocytes in the lung, followed by pulmonary vascular injury, as indicated by an increase in the pulmonary vascular permeability, and coagulation abnormalities. The dose of 250 U/kg significantly inhibited all such effects of endotoxin. While lower doses of antithrombin III (50 and 100 U/kg) significantly inhibited such coagulation abnormalities, they failed to prevent either the pulmonary accumulation of leukocytes or the subsequent pulmonary vascular injury. Rats administered endotoxin exhibited an accumulation of neutrophils and edematous changes in the pulmonary interstitial space. Although such changes were reduced after 250 U/kg of antithrombin III, they were unaffected by lower doses of 50 and 100 U/kg. Plasma levels of 6-keto-PGF1alpha were markedly increased in rats 90 min after the administration of endotoxin, and were significantly decreased in the endotoxin-treated rats administered the lower doses of antithrombin III (50 and 100 U/kg), but not altered in those endotoxin-treated rats receiving 250 U/kg of antithrombin III. These findings suggest that a higher antithrombin III dose is necessary to prevent endothelial cell injury than is required to inhibit coagulation abnormalities in an animal model of sepsis. These observations support the notion that antithrombin III may prevent endotoxin-induced endothelial cell injury by promoting endothelial release of prostaglandin I2 and thus inhibiting leukocyte activation.
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PMID:Effects of various doses of antithrombin III on endotoxin-induced endothelial cell injury and coagulation abnormalities in rats. 964 17


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