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

Gram-negative septic shock remains a major clinical problem. One frequently encountered complication of sepsis is disseminated intravascular coagulation (DIC). The present study was to determine in an Escherichia coli endotoxemia awake rat model the efficacy of antithrombin-III (AT-III) prophylaxis and to explore the role of DIC in the pathogenesis of endotoxemia. We demonstrated that DIC occurs very early, before the appearance of detectable serious abnormalities in cardiovascular, metabolic, and biochemical variables indicative of organ damage or dysfunction; AT-III prophylaxis significantly ameliorates DIC, as evidenced by completely preventing the fall in plasma fibrinogen concentration and significantly limiting the increases in prothrombin time and activated partial thromboplastin time after 4 hours of endotoxemia; and AT-III prophylaxis dramatically increases permanent survival. Results of this study suggest that AT-III prophylaxis is very protective above a threshold dosage in an endotoxemic rat model and that protection is in part due to ameliorating DIC. Our data also suggest that DIC occurs very early during endotoxemia and may in part be responsible for the pathogenesis of endotoxemia in the rat. We conclude that AT-III prophylaxis may be efficacious in conditions of impending DIC, such as gram-negative septicemia/endotoxemia.
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PMID:Protection against disseminated intravascular coagulation and death by antithrombin-III in the Escherichia coli endotoxemic rat. 354 29

In a controlled study of fibronectin supplementation in sepsis, 11 ICU patients in septic shock were scheduled to receive either cryoprecipitate from 20-40 donors (n = 6) or 250-300 ml of stored plasma (n = 5) (two infusions over 24 h). We wanted to: compare some "conventional" DIC variables in the ICU (platelet count, prothrombin complex = NT, FDP) to additional variables: Fibronectin (Fn), fibrinogen (Fg), F V, FVIII R:Ag, F VIII:C activity, F XII, plasminogen (Plg), antiplasmin (AP), antithrombin (AT), kallikrein inhibiting activity (KI) and spontaneous proteolytic activity (SPA): study the effects of cryoprecipitate or plasma infusion on three variables. Samples were taken before the first infusion, and 24 and 48 h after. At onset, high levels (p less than .001 when compared to blood donors) of Fg, VIIIR:Ag and VIII:C were seen. KI levels were within the normal range. F V was low (p less than .05). Fn, NT, XII, Plg, AP and AT were markedly low (p less than .001). SPA showed great variation. When compared to 28 patients with severe infections, but not in septic shock, the ICU group had higher VIIIR:Ag (p less than .05) and VIII:C (p less than .01), and lower XII, Plg, AP and AT (p less than .001). FDP was elevated in all ICU patients. Five patients were thrombocytopenic, and in these a pattern with low levels of Plg and AT was observed. Fn did not correlate well to the other variables measured. These results indicate a marked activation of coagulation and fibrinolysis in these severely ill patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fibronectin and other DIC-related variables in septic ICU patients receiving cryoprecipitate. 393 20

Gabexate mesilate (FOY), a synthetic serine proteinase inhibitor, has an anticoagulant activity in the absence of antithrombin-III. We investigated FOY therapy for the treatment of disseminated intravascular coagulation (DIC) associated with sepsis in 15 patients (group F), and compared it with heparin therapy in 8 patients (group H). Successful treatment was observed in 13 patients in group F and in 4 patients in group H. The efficacy of the therapy in both groups was not significantly different. However, in patients whose antithrombin-III values were less than 20 mg/dl at the initiation of the therapy, FOY therapy was successful in 6 of 7 patients, whereas heparin therapy was not at all successful in 4 patients (rho less than 0.05). We conclude that FOY can be used as effectively as heparin for the treatment of DIC, and that FOY therapy is superior to heparin therapy in DIC associated with decreased antithrombin-III.
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PMID:Gabexate mesilate (FOY) therapy of disseminated intravascular coagulation due to sepsis. 641 32

A case of excessive heparin requirement during cardiopulmonary bypass is reported. A patient with sepsis secondary to a myocardial abscess require 13.5 mg x kg-1 of heparin to increase his activated coagulation time to a therapeutic level. This phenomenon might be due to individual variability, lupus vasculitis, septicaemia, repeated thromboembolic phenomenon with hypercoagulable state, or chronic disseminated intravascular coagulation with partial antithrombin deficiency.
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PMID:Excessive requirement for heparin during cardiac surgery. 723 24

To obtain quantitative information on the in vivo activation of the protein C system during the acute phase of sepsis, several components of the protein C pathway were studied in 18 patients. Blood samples were obtained one day after diagnosis (day 1) and, in 11 patients, also on the fourth and tenth days after diagnosis (days 4 and 10). On day 1, patients showed laboratory signs of haemostatic alterations such as positive fibrinogen/fibrin degradation products, and increased thrombin:antithrombin-III (TAT) complex levels. Compared with the control group, patients on day 1 had significantly decreased (p < 0.001) antigenic protein C (69 +/- 28%) and protein C inhibitor (PCI) (33 +/- 22%) whereas a significant increase in the levels of activated protein C (APC) complexed with alpha 1-antitrypsin (alpha 1AT) (APC:alpha 1AT, 26 +/- 15 ng/mL) and APC:PCI complex (3.0 +/- 2.0 ng/mL), and in the level of plasma kallikrein (KK) complexes with PCI (KK:PCI) (31 +/- 22 ng/mL) was observed. There was a positive correlation between APC:alpha 1AT and TAT complex levels (r = 0.597, p = 0.009). In the follow-up a trend toward normal values in antigenic protein C and PCI, and in APC:PCI and KK:PCI complex levels was found. However, PCI remained significantly decreased compared to normal values. C4b-binding protein, alpha 1AT, and TAT and APC:alpha 1AT complexes did not show any significant variations during the course of the disease, suggesting the contribution of the inflammatory and haemostatic responses, in spite of the good recovery of the patients. This study shows that in the course of sepsis, patients experience a generalized activation of the protein C pathway which was more prominent on day 1, resulting in the consumption of protein C and PCI and in the increase of APC:inhibitor complexes. Moreover, these data provide further evidence that KK:PCI circulating complexes occur in vivo.
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PMID:Activation of the protein C pathway in acute sepsis. 749 7

Excessive coagulation is a typical response to the vascular injury occurring in gram negative sepsis. This study evaluated the pharmacological effects of the use of a recombinant Escherichia coli derived form of tissue factor pathway inhibitor (ala-TFPI) in a baboon model of septic shock. Several doses of ala-TFPI were administered either 30 or 120 min after the initiation of a lethal intravenous infusion of E. coli into baboons. Treatment at 30 min with either 2.7 or 7.4 mg/kg of ala-TFPI resulted in the same survival rates and attenuation of both the coagulation response and cellular injury, as measured by clinical chemistry. When administration of ala-TFPI was delayed for 120 min, a dose of ala-TFPI protein continued to provide a benefit to survival. Ala-TFPI reduced the drop in mean systemic arterial pressure compared to control baboons in addition to partially attenuating the coagulopathic response. Baboons given ala-TFPI also maintained lower levels of plasma interleukin-6 (IL-6) and thrombin-antithrombin. These results suggest that the site of action of the protein may involve the later stage components of the coagulation and inflammatory pathways.
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PMID:Recombinant E. coli-derived tissue factor pathway inhibitor reduces coagulopathic and lethal effects in the baboon gram-negative model of septic shock. 760 Jun 36

In septic patients capable of normal white cell responses, high plasma levels of PAI-I, t-PA antigen and t-PA-PAI-I complex were observed. The ratios of t-PA and PAI-I were such that free PA activity was almost never observed. In patients severely leucopenic prior to becoming septic the changes were significantly less marked, so presence of leucocytes enhances the fibrinolytic inhibition occurring in sepsis. The non-leucopenic septic group showed greater evidence of thrombin generation in that FPA levels were higher but fibrinogen levels were only slightly less and antithrombin levels not different from those in the leucopenic group. A greater tendency to fibrin deposition and the striking fibrinolytic inhibition noted in patients with normal white cell responses may contribute to the development of some of the complications of sepsis in which fibrin deposition participates and may explain their relative rarity in leucopenic patients. When shock supervened, levels of PAI-I were high in both leucopenic and non-leucopenic groups, indicating that a source of PAI-I outwith the leucocytes themselves contributes to the phenomena observed.
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PMID:Influence of white blood cells on the fibrinolytic response to sepsis: studies of septic patients with or without severe leucopenia. 764 91

To date no single agent has emerged as the treatment of choice for the management of septic shock and it is becoming increasingly clear that in future it will prove necessary to combine treatments to provide the optimum therapy. One group of agents that should theoretically prove beneficial in sepsis are the protease inhibitors, antithrombin being the one most widely investigated to date. This article discusses the evidence supporting its use in the treatment of septicaemia.
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PMID:The clinical use of antithrombin concentrate in septicaemia. 771 80

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.
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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.
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PMID:Coagulation, fibrinolytic and kallikrein systems in neonates with uncomplicated sepsis and septic shock. 827 17


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