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

Sepsis is characterized by a concurrent activation of inflammation and coagulation. Recently, recombinant human activated protein C was shown to decrease mortality in patients with severe sepsis presumably due to a combined anti-inflammatory and anticoagulant effect. These promising findings led to a search for other products that influence both the inflammatory and the procoagulant response to severe infection. Ethyl pyruvate (EP) was recently identified as an experimental anti-inflammatory agent during endotoxemia and sepsis. The aim of the present study was to investigate whether EP influences coagulation besides its anti-inflammatory effects. For this we investigated the effects of EP on the expression and function of tissue factor (TF), the principal initiator of coagulation activation in sepsis, in human monocytic (THP-1) cell cultures. EP dose-dependently inhibited the production of tumor necrosis factor (TNF)-alpha, macrophage inflammatory protein (MIP)-1alpha and MIP-1beta by lipopolysaccharide (LPS)-stimulated THP-1 cells at mRNA and protein level, thereby confirming its anti-inflammatory properties in this in-vitro system. In addition, EP dose-dependently attenuated the increases in TF mRNA levels, TF-protein-surface expression and cell-surface-associated TF activity in LPS-stimulated THP-1 cells. These results demonstrate for the first time that EP is a compound with combined anti-inflammatory and anticoagulant effects.
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PMID:Ethyl pyruvate exerts combined anti-inflammatory and anticoagulant effects on human monocytic cells. 1713 74

The purpose of this study was to describe the clinical characteristics of cats with disseminated intravascular coagulation (DIC), including associated diseases and hemostatic abnormalities, and to identify risk factors for death and treatments that potentially altered outcome. Medical records for cats with DIC from 1990-2004 were evaluated retrospectively. Inclusion criteria were the presence of an underlying disorder associated with DIC and either postmortem examination findings of intravascular fibrin deposition or thrombosis, or both of 2 or more organs or coagulation profiles that meet 3 of 5 criteria: prolonged prothrombin time (PT), activated partial thromboplastin time (aPTT), presence of fibrin degradation products (FDP), low plasma fibrinogen (FIB) concentration, and thrombocytopenia (<160,000 platelets/microL). Signalment, historical data, clinical findings, clinicopathologic data, underlying disorders, management, and outcome were recorded. Forty-six cats fulfilled the criteria for DIC. Cats ranged in age from 7 weeks to 17 years (median, 9 years). Hemorrhage was noted in 7 of 46 cats (15%). Three of 46 cats (7%) survived, whereas 43 of 46 (93%) died or were euthanized. The most common underlying disorders were lymphoma, other forms of neoplasia, pancreatitis, and sepsis. There was no association detected between outcome and signalment; underlying disease; hemorrhage; abnormalities in aPTT, FIB, FDPs, platelet count; transfusion of blood products; and heparin therapy. However, the median PT of nonsurvivors was more prolonged than in survivors (P < .005). DIC in cats can result from a variety of neoplastic, infectious, and inflammatory disorders, and is associated with a high case fatality rate.
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PMID:Disseminated intravascular coagulation in cats. 1718 39

The biphasic waveform (BPW) is an abnormality of the optical transmission waveform obtained during measurement of the activated partial thromboplastin time on a specific photometric haemostasis autoanalyzer. This abnormality is related to calcium-dependent formation of complexes between C reactive protein and very low density lipoprotein. Biphasic waveform had a high sensitivity and negative predictive value for the identification of patients with severe sepsis and septic shock. On day 3, the time course of the biphasic waveform is a marker for the prognosis of sepsis-related mortality. The BPW is not a surrogate marker for C-reactive protein or procalcitonin and provides additional information. Further trials should be necessary using BPW for diagnostic and management procedures. Compared with other laboratory markers such as C reactive protein or procalcitonin, activated partial thromboplastin time waveform analysis is a tool that is rapid, inexpensive, effective and available 24 hours a day. When the analyzer is locally available, waveform analysis of this routine coagulation test provides information for the diagnosis of severe sepsis and the prognosis of septic patients.
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PMID:[The abnormal activated partial thromboplastin time biphasic waveform: a red flag in the sepsis? Technique and interest as marker of the sepsis]. 1725 26

Tissue factor (TF) is the primary initiator of coagulation, and the TF pathway mediates signaling through protease-activated receptors (PARs). In sepsis, TF is up-regulated as part of the proinflammatory response in lipopolysaccharide (LPS)-stimulated monocytes leading to systemic coagulation activation. Here we demonstrate that TF cytoplasmic domain-deleted (TF(Delta CT)) mice show enhanced and prolonged systemic coagulation activation relative to wild-type upon LPS challenge. However, TF(Delta CT) mice resolve inflammation earlier and are protected from lethality independent of changes in coagulation. Macrophages from LPS-challenged TF(Delta CT) mice or LPS-stimulated, in vitro-differentiated bone marrow-derived macrophages show increased TF mRNA and functional activity relative to wild-type, identifying up-regulation of macrophage TF expression as a possible cause for the increase in coagulation of TF(Delta CT) mice. Increased TF expression of TF(Delta CT) macrophages does not require PAR2 and is specific for toll-like receptor, but not interferon gamma receptor, signaling. The presence of the TF cytoplasmic domain suppresses ERK1/2 phosphorylation that is reversed by p38 inhibition leading to enhanced TF expression specifically in wild-type but not TF(Delta CT) mice. The present study demonstrates a new role of the TF cytoplasmic domain in an autoregulatory pathway that controls LPS-induced TF expression in macrophages and procoagulant responses in endotoxemia.
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PMID:Regulation of macrophage procoagulant responses by the tissue factor cytoplasmic domain in endotoxemia. 1733 47

World wide, heparins are the most commonly used anticoagulants for renal replacement therapy (RRT). In the intensive care unit (ICU) keeping the RRT circuit patent is more difficult than during routine outpatient hemodialysis, as ICU patients typically have sepsis and/or inflammation resulting in activation of the procoagulant pathways, with reduced antithrombin. One important cause of repeated RRT circuit clotting is heparin-induced thrombocytopenia (HIT), which should not be overlooked in patients with a reduced platelet count. If HIT is clinically suspected then all heparins should be withdrawn, and the patient systemically anticoagulated with either a direct thrombin inhibitor, such as argatroban and/or hirudin, or the heparinoid danaparoid. The availability and licensing of these alternative anticoagulants varies from country to country. Argatroban has to be continuously infused, which is an advantage for continuous RRT, but not for intermittent RRT, and can be monitored by activated partial thromboplastin time. Hirudin has a prolonged half life, which is extended by hirudin antibodies, and requires specialist monitoring to prevent over anticoagulation. Although the half life of danaparoid is increased in renal failure, it can be given as boluses for intermittent and continuous RRT, or by continuous infusion during continuous RRT, but requires factor Xa monitoring.
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PMID:Anticoagulation options for patients with heparin-induced thrombocytopenia requiring renal support in the intensive care unit. 1746 35

Pulmonary coagulopathy and hyperinflammation may contribute to an adverse outcome in sepsis. The present study determines the effects of natural inhibitors of coagulation on bronchoalveolar haemostasis and inflammation in a rat model of endotoxaemia. Male Sprague-Dawley rats were randomised to treatment with normal saline, recombinant human activated protein C (APC), plasma-derived antithrombin (AT), recombinant human tissue factor pathway inhibitor (TFPI), heparin or recombinant tissue plasminogen activator (tPA). Rats were intravenously injected with lipopolysaccharide (LPS), which induced a systemic inflammatory response and pulmonary inflammation. Blood and bronchoalveolar lavage were obtained at 4 and 16 h after LPS injection, and markers of coagulation and inflammation were measured. LPS injection caused an increase in the levels of thrombin-AT complexes, whereas plasminogen activator activity was attenuated, both systemically and within the bronchoalveolar compartment. Administration of APC, AT and TFPI significantly limited LPS-induced generation of thrombin-AT complexes in the lungs, and tPA stimulated pulmonary fibrinolytic activity. However, none of the agents had significant effects on the production of pulmonary cytokines, chemokines, neutrophil influx and myeloperoxidase activity. Natural inhibitors of coagulation prevent bronchoalveolar activation of coagulation, but do not induce major alterations of the pulmonary inflammatory response in rat endotoxaemia.
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PMID:Natural anticoagulants limit lipopolysaccharide-induced pulmonary coagulation but not inflammation. 1753 62

To investigate clinical course and outcome of dengue with acute respiratory failure (ARF), and to identify related risk factors for acquiring ARF in dengue, we retrospectively studied 11 dengue patients with ARF. From June to December 2002, a total of 606 adult patients were diagnosed as having dengue. Eleven (1.8%) of 606 dengue patients had complications of ARF. The main causes of ARF were sepsis (n = 6, 54.5%) and upper gastrointestinal (UGI) bleeding (n = 3, 27.3%). The mortality rate was 72.7% (n = 8). Additionally, univariate analysis showed that age, dyspnea, cough, prothrombin time, activated partial thromboplastin time, aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, creatinine, albumin, renal insufficiency, acute renal failure, acute hepatic failure, UGI bleeding, and combination bacterial infection were significantly predictive variables associated with dengue patients with ARF.
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PMID:Acute respiratory failure in adult patients with dengue virus infection. 1762 Jun 47

Systemic hemostatic activation following primary intracerebral hemorrhage (PICH) has been described, particularly with intraventricular or subarachnoid extension. Our objective was to study the occurrence of abnormalities of coagulation as measured by partial thromboplastin time, international normalized ratio, and platelet count in patients with PICH and no obvious cause for a pre-existing coagulopathy. Charts of PICH patients admitted between November 1991 and December 2001 were reviewed. We excluded patients with an underlying lesion, cranial trauma, anticoagulation, liver failure or sepsis. All patients had partial thromboplastin time, international normalized ratio, and platelet count measured on admission. An international normalized ratio > 1.4, partial thromboplastin time > 35, and platelet count < 100,000 were considered abnormal based on standardized values for our laboratory. All patients underwent a computed tomography (CT) scan on admission. Repeat CT was obtained for evidence of neurological deterioration. One hundred ninety-two patients with intracerebral hemorrhage were studied. Thirty-seven were excluded because of a possible underlying cause for a pre-existing coagulopathy. Thirteen of one hundred and fifty-five (8.4%) patients were found to have a coagulopathy based on our criteria. Three of thirteen (23%) patients with coagulopathy versus 3/142 (2%) without suffered neurological deterioration with evidence of hematoma enlargement (P = .008). Eleven of sixty-seven (17%) patients with intraventricular/subarachnoid extension versus 2/88 (2%) without had a coagulopathy (P = .002). Eight of thirteen (61%) patients with coagulopathy versus 29/142 (20%) without were dead at 30 days (P = .003). Coagulation abnormalities without an obvious etiology that may be consistent with low grade disseminated intravascular coagulation are seen in 8.4% of patients with PICH and are associated with extension into the subarachnoid and intraventricular compartments, neurological deterioration with hematoma expansion, and mortality at 30 days. This may represent a target for therapeutic intervention.
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PMID:Coagulation abnormalities following primary intracerebral hemorrhage. 1790 49

Tissue factor (TF) is an important regulator and effector molecule of coagulation. It is primary known as a cofactor for factor VIIa-mediated triggering of blood coagulation, which proceeds in a cascade of extracellular reactions, ultimately resulting in thrombin formation. In sepsis, expression of TF by activated monocytes, macrophages and endothelial cells may lead to disseminated intravascular coagulation. Further studies have suggested that TF also plays non-haemostatic roles in blood vessel development, tumor angiogenesis, metastasis and inflammation. In the present study we examined the feasibility of inhibiting lipopolysaccharide (LPS)-induced TF expression in cultured human umbilical vein endothelial cells (HUVECs) using a modified phosphorothioate antisense oligodeoxynucleotide targeted to the TF mRNA. CD31 receptor-mediated endocytosis was used as a means of delivering TF antisense oligomer to HUVECs. This DNA carrier system consists of anti-CD31 antibody conjugated to the antisense. Co-exposure of HUVECs with TF antisense and LPS resulted in 54.6+/-3.2% suppression of TF activity when compared with control LPS stimulated cells. The antisense also reduced the LPS-induced TF mRNA level. Control experiments with TF sense and mismatched antisense oligomers were performed to exclude non-specific inhibitory effects. The cytotoxicity of the antisense oligomer conjugate was also evaluated. Results demonstrate that this TF antisense oligomer specifically suppressed the synthesis of biologically active endothelial TF and that antisense oligomers might represent a useful tool in the investigation of endothelial TF function/biology.
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PMID:Suppression of HUVEC tissue factor synthesis by antisense oligodeoxynucleotide. 1792 Jun 61

Venous thrombosis can be the source of emboli, a significant health risk encountered throughout surgical and medical clinics. Taurolidine is an antimicrobial agent used to prevent intraabdominal adhesion formation and sepsis in experimental and clinical trials. The aim of this study is to evaluate effect of taurolidine on experimental thrombus formation and make a comparison with low-molecular weight heparin. Four groups of ten Wistar-Albino rats (300-350 g) were used; with the first and second groups each being administered 10 and 20 mg of taurolidine, the third group low-molecular weight heparin and the fourth group saline solution (control group) respectively. Experimental thrombus formation was performed in rats in the area of the abdominal inferior vena cava by using a combination of stasis and hypercoagulability described by Wessler et al. [Wessler, S., Reimer, S.M., Sheps, M.C., 1959. Biologic assay of a thrombosis inducing activity in human serum. J. Appl. Physiol. 14:943-946.]. Thrombocyte count, the weight of thrombus, prothrombin time and activated partial thromboplastin time and activities of coagulation factors were measured and compared across groups. Thrombus weights in the taurolidine treated groups were lower than the control group and greater than the low-molecular weight heparin treated group. Taurolidine was found to decrease activities of coagulation factors V, VIII, IX, XI and XII. Taurolidine showed no effect on activated partial thromboplastin time and prothrombin time values; however, it decreased thrombus weight, but not as much as low-molecular weight heparin. The cause of these findings in our study may be related to the minimized effect of taurolidine on factor II, VII, and X activities. These effects likely render the agent ineffective in the prevention of venous thrombosis. Taurolidine was found to be less effective than low-molecular weight heparin in prevention of thrombus formation.
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PMID:The effect of taurolidine on experimental thrombus formation. 1796 49


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