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

The organic symptoms and results of coagulation tests of disseminated intravascular coagulopathy (DIC) in 17 patients with infection were compared with those in 12 patients with malignancy. The infectious diseases were mainly sepsis and pneumonia, and the malignancy was mainly lung cancer. The mean antithrombin III (AT III) before treatment was 54% in infection and 68% in malignancy, and the AT III values improved after administration of 1500 U of AT III concentrates per day. The mean thrombin-antithrombin complex level decreased from 22 ng/ml to 9 ng/ml after the treatment in infection, but it increased in malignancy. There were no differences in DIC scores between infection and malignancy before treatment; however, the scores were significantly more improved in infection than in malignancy after treatment (p < 0.05). The fibrin/fibrinogen degradation product level, platelet count, and fibronectin level were also significantly more improved in infection than in malignancy. This better response to treatment in infection than in malignancy is probably due to eradication of the causative organisms by antibiotics in infection. These data suggest that therapy against both DIC and the underlying disease is crucial for successful treatment.
 ...
PMID:Disseminated intravascular coagulopathy in infection compared with that in malignant neoplasia. 774 1

This study evaluates the contact system, coagulation inhibitors and fibrinolysis in 23 full-term newborns with sepsis (8 with septic shock). The results were compared with a group of 20 healthy newborns. Blood samples were obtained at the time of clinical diagnosis and 3 days after the antibiotic therapy was started. The results showed that: severe infection was associated with activation of the contact system, depletion of anticoagulant proteins and elevation of C4b-binding protein levels. There was a shift in protein S to the complexed inactive form, and the thrombin-antithrombin complexes increased. These changes occurred in parallel to both activation and inhibition of fibrinolysis. These changes were more pronounced in the septic shock patients than in nonshock neonates. After therapy, this procoagulant state decreased among survivor patients while in those who died, the abnormalities in coagulation did not improve. Our study suggests that neonatal sepsis induces a hypercoagulable state that persists in nonsurvivor neonates despite a correct treatment.
 ...
PMID:Coagulation, fibrinolytic and kallikrein systems in neonates with uncomplicated sepsis and septic shock. 827 17

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.
 ...
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.
 ...
PMID:Age-related differences in outcome and severity of DIC in children with septic shock and purpura. 897 13

An animal model of gram-positive septicemia was developed to evaluate the effects of antithrombin (AT) concentrates on morbidity, mortality, and laboratory consequences of disseminated intravascular coagulation (DIC). DIC was induced in guinea pigs by infusing Staphylococcus aureus (SA) isolated from blood cultures of patients with DIC (DIC-SA) or without DIC (non-DIC-SA). The non-DIC-SA animals and animals infused with sterile saline served as controls. Varying doses of AT were administered either 30 minutes or 24 hours after infusion of SA. DIC was confirmed within 4 hours by changes in prothrombin time, activated partial thromboplastin time, fibrinogen, fibrinogen-fibrin degradation products, and AT activity. Clinical bleeding was also evident. Mortality of untreated DIC-SA animals was 36% within 24 hours and up to 75% by 72 hours. Intervention with any dose of AT between 125 and 1,000 IU/kg 30 minutes after DIC-SA infusion was associated with 100% survival (P < or = .05 in the 250 IU/kg group) and sustained increases in AT activity and fibrinogen concentrations (P < or = .05). When AT was administered in combination with low molecular weight heparin (LMWH) or if LMWH was adminstered alone, mortality from DIC-SA was slightly, but not significantly reduced compared with untreated DIC-SA. Gross hemorrhage was observed premortem and at autopsy in all of the DIC-SA animals but in substantially fewer animals that received AT (P < or = .001 in the 250, 500, and 1,000 IU/kg groups). In contrast, groups treated with LMWH, alone or with AT, experienced hemorrhage and appeared to develop pathologic DIC. Fibrin formation in end-organs was detected in all guinea pigs in the untreated DIC-SA group and in the groups treated with 125 IU/kg AT and LMWH alone. AT doses between 250 and 1,000 IU/kg administered 30 minutes after DIC-SA infusion prevented fibrin formation in end-organs (P < or = .001 in the 250 and 1,000 IU/kg groups). AT administered 24 hours after DIC-SA could not reverse pre-existing histopathologic evidence of DIC but favorably affected survival, which reached statistical significance in the 1,000 IU/kg AT group (P < or = .025). In summary, suprapharmacologic doses of AT concentrate significantly decreased morbidity and mortality and ameliorated adverse changes in laboratory measures induced by DIC-SA in this guinea pig model and were not associated with untoward hemorrhagic complications. These findings provide justification for studying the use of AT therapy in patients with DIC-SA.
 ...
PMID:The suprapharmacologic dosing of antithrombin concentrate for Staphylococcus aureus-induced disseminated intravascular coagulation in guinea pigs: substantial reduction in mortality and morbidity. 919 63

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.
 ...
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.
 ...
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.
 ...
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.
 ...
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.
 ...
PMID:Antithrombin: its physiological importance and role in DIC. 951 76


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>