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

Staphylococcus aureus is one of the most significant pathogens in human sepsis and endocarditis. A hallmark of these endovascular S. aureus infections is that the coagulation system is triggered by a tissue factor (TF)-dependent pathway. This study demonstrates that highly purified S. aureus peptidoglycan, lipoteichoic acid (LTA) and TSST-1 increase TF mRNA and TF surface protein in human umbilical vein endothelial cells (ECs). Concomitantly, peptidoglycan- and LTA-activated ECs express significant TF-dependent procoagulant activity (TF PCA). In addition peptidoglycan, but not LTA or TSST-1, induced surface expression of the EC inflammation markers ICAM-1 and VCAM-1, which supported the adhesion of monocytes to these ECs. During the coculture of peptidoglycan-activated ECs and adherent monocytes, a marked additional increase of TF PCA was observed. Marginal increases in TF PCA were observed in cocultures of monocytes with LTA- or TSST-1-activated ECs. This study defines in particular staphylococcal peptidoglycan, previously known as a potent initiator of TF PCA in monocytes, as also being an activator of a coagulant response in human ECs that is further intensified by the presence of surface-bound monocytes.
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PMID:Staphylococcal peptidoglycan initiates an inflammatory response and procoagulant activity in human vascular endothelial cells: a comparison with highly purified lipoteichoic acid and TSST-1. 1803 38

Recent clinical studies have shown a sex dimorphism of morbidity and mortality due to shock, trauma, and sepsis, with females tolerating these insults better than males. Experimental animal studies have suggested that sex hormones have a pivotal role in this dimorphism. In the present investigation, a prospective cohort study at a university level-1 trauma center was conducted to evaluate the association between sex hormones and alterations in coagulation and inflammation. Patients with an admission to the intensive care unit, injury severity score (ISS) greater than 4, and obtainable consent were included in the study. In addition to routine clinical laboratories and patient outcomes, plasma TNF-[alpha], IL-6, IL-8, estradiol, progesterone, and testosterone were measured. Sixty-two patients (71% men, 29% women) met criteria for entry. Mean age was 42 +/- 17 years, and mean ISS was 23 +/- 13, with no statistical difference in age or ISS between sexes. Estradiol levels were positively correlated with ISS (P < 0.05) and negatively correlated with TNF-[alpha] (P < 0.01). Initial estradiol levels were higher in patients who developed an infection (P < 0.05). Testosterone was negatively correlated with age (P < 0.01) and was higher in patients who developed acute respiratory distress syndrome (P < 0.05) and in patients who did not survive (P < 0.05). The estradiol-to-progesterone ratio (E2-Pr) was higher in the survivors (P < 0.05). The E2-Pr had positive correlations with fibrinogen levels, rate of fibrin deposition and cross-linking, and overall clot strength (P < 0.05). Estradiol-to-progesterone ratio was negatively correlated with partial thromboplastin times (P < 0.01). In men, the E2-Pr was also negatively correlated with the time to onset of clot formation (P = 0.03). Sex hormone levels (or their ratios) were not correlated to platelet count or international normalized ratios. These findings provide evidence that sex hormone levels in the early posttraumatic period are significantly associated with alterations in the hemostatic and inflammatory response to trauma.
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PMID:The influence of sex hormones on coagulation and inflammation in the trauma patient. 1843 14

Transmittance waveform (TW) analysis has been proposed as a method of both prediction and monitoring of non-overt and overt disseminated intravascular coagulation. This study assessed the use of the rapidTW of the activated partial thromboplastin time in the detection of sepsis in 49 consecutive neutropenic haemato-oncology patients. A slope 1 cut-off value of -0.050 was found to be optimum giving 85% sensitivity with 92% specificity and positive and negative predictive values of 62% and 98%, respectively. Furthermore a worsening slope 1 value at 24 hours was indicative of a 60% increase in mortality risk. Haemato-oncology patients have a significantly increased risk of developing sepsis during intensive chemotherapy, exacerbated by the resultant neutopenia. This sepsis may progress extremely rapidly and is associated with a high mortality. Early diagnosis is therefore critical and is currently made on a predominantly clinical basis with supporting microbiological evidence 2-3 days later. This study showed that TW offers an early marker, predictive of sepsis in neutropenic patients. It correlates with subsequent microbiological results and may identify patients at greater risk of clinical deterioration who may require more intensive early therapy or observation. It may also provide a useful marker to monitor the effects of treatment.
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PMID:The biphasic transmittance waveform: an early marker of sepsis in patients with neutropenia. 1861 29

The activated partial thromboplastin time (APTT) is the most common coagulation test procedure performed in routine laboratories, apart from the prothrombin time. The test is traditionally used for identifying quantitative and qualitative abnormalities in the intrinsic and common pathways of coagulation, monitoring anticoagulant therapy with unfractionated heparin, and detecting inhibitors of blood coagulation, the most common of which is the lupus anticoagulant. Whereas short APTT values have been mostly overlooked in the past, recent evidence suggests that these might be associated with hypercoagulability. Although clinical relevance is yet to be clearly defined, hypercoagulability detected by a shortened APTT appears to be significantly associated with a major risk of venous thromboembolism independently from other variables such as blood group, the presence of inherited thrombophilia, and factor VIII levels. This novel finding suggests that this traditional, simple, and inexpensive test might have renewed utility along with traditional thrombophilic tests in the evaluation of venous thromboembolic risk. In addition, APTT waveform analysis is also providing mounting evidence of added utility, in particular for identifying sepsis and disseminated intravascular coagulation in critically ill patients (particularly where this might worsen the prognosis), for monitoring therapy in patients with inhibitors, and as a diagnostic aid to identify patients with antiphospholipid antibodies. In total, such emerging evidence suggests that the APTT is either an old dogma displaying new tricks or else might describe a new dogma for an old laboratory trick.
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PMID:Activated partial thromboplastin time: new tricks for an old dogma. 1908 61

The diagnosis of disseminated intravascular coagulation (DIC) should encompass both clinical and laboratory information. The International Society for Thrombosis and Haemostasis (ISTH) DIC scoring system provides objective measurement of DIC. Where DIC is present the scoring system correlates with key clinical observations and outcomes. It is important to repeat the tests to monitor the dynamically changing scenario based on laboratory results and clinical observations. The cornerstone of the treatment of DIC is treatment of the underlying condition. Transfusion of platelets or plasma (components) in patients with DIC should not primarily be based on laboratory results and should in general be reserved for patients who present with bleeding. In patients with DIC and bleeding or at high risk of bleeding (e.g. postoperative patients or patients due to undergo an invasive procedure) and a platelet count of <50 x 10(9)/l transfusion of platelets should be considered. In non-bleeding patients with DIC, prophylactic platelet transfusion is not given unless it is perceived that there is a high risk of bleeding. In bleeding patients with DIC and prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT), administration of fresh frozen plasma (FFP) may be useful. It should not be instituted based on laboratory tests alone but should be considered in those with active bleeding and in those requiring an invasive procedure. There is no evidence that infusion of plasma stimulates the ongoing activation of coagulation. If transfusion of FFP is not possible in patients with bleeding because of fluid overload, consider using factor concentrates such as prothrombin complex concentrate, recognising that these will only partially correct the defect because they contain only selected factors, whereas in DIC there is a global deficiency of coagulation factors. Severe hypofibrinogenaemia (<1 g/l) that persists despite FFP replacement may be treated with fibrinogen concentrate or cryoprecipitate. In cases of DIC where thrombosis predominates, such as arterial or venous thromboembolism, severe purpura fulminans associated with acral ischemia or vascular skin infarction, therapeutic doses of heparin should be considered. In these patients where there is perceived to be a co-existing high risk of bleeding there may be benefits in using continuous infusion unfractionated heparin (UFH) due to its short half-life and reversibility. Weight adjusted doses (e.g. 10 mu/kg/h) may be used without the intention of prolonging the APTT ratio to 1.5-2.5 times the control. Monitoring the APTT in these cases may be complicated and clinical observation for signs of bleeding is important. In critically ill, non-bleeding patients with DIC, prophylaxis for venous thromboembolism with prophylactic doses of heparin or low molecular weight heparin is recommended. Consider treating patients with severe sepsis and DIC with recombinant human activated protein C (continuous infusion, 24 microg/kg/h for 4 d). Patients at high risk of bleeding should not be given recombinant human activated protein C. Current manufacturers guidance advises against using this product in patients with platelet counts of <30 x 10(9)/l. In the event of invasive procedures, administration of recombinant human activated protein C should be discontinued shortly before the intervention (elimination half-life approximately 20 min) and may be resumed a few hours later, dependent on the clinical situation. In the absence of further prospective evidence from randomised controlled trials confirming a beneficial effect of antithrombin concentrate on clinically relevant endpoints in patients with DIC and not receiving heparin, administration of antithrombin cannot be recommended. In general, patients with DIC should not be treated with antifibrinolytic agents. Patients with DIC that is characterised by a primary hyperfibrinolytic state and who present with severe bleeding could be treated with lysine analogues, such as tranexamic acid (e.g. 1 g every 8 h).
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PMID:Guidelines for the diagnosis and management of disseminated intravascular coagulation. British Committee for Standards in Haematology. 1922 77

Inflammation and coagulation occur concomitantly in sepsis. Thrombin activates platelet that leads to P-selectin translocation, which upregulate tissue factor (TF) generation. Tissue factor pathway inhibitor (TFPI) is an anticoagulant that modulates coagulation induced by TF. The term non-overt disseminated intravascular coagulation (DIC) refers to a state of affairs prevalent before the occurrence of overt DIC. It was suggested that an initiation of treatment in non-overt DIC has better outcome than overt DIC. This study investigated the role of TFPI level, P-selectin, and thrombin activation markers in non-overt and overt DIC induced by sepsis and its relationship to outcome and organ dysfunction as measured by the Sequential Organ Failure Assessment (SOFA) score. It included 176 patients with sepsis. They were admitted to the pediatric intensive care unit (ICU).They included 144 cases of non-overt DIC and 32 cases of overt DIC. There was a significant difference in hemostatic markers, platelet count, partial thromboplastin time (PTT), P-selectin, thrombin activation markers, TFPI, and DIC score between overt and non-overt DIC in both groups. It was noticed that P-selectin was positively correlated with DIC score, fibrinogen consumption, fibrinolysis (D-dimer), thrombin activation markers, and TFPI. Tissue factor pathway inhibitor was significantly correlated with fibrinolysis, DIC score, and prothrombin fragment 1+2. Sequential Organ Failure Assessment score was correlated with DIC score and other hemostatic markers in patients with overt DIC. To improve the outcome of patients with DIC, there is a need to establish more diagnostic criteria for non-overt-DIC. Plasma levels of TFPI and P-selectin may be helpful in this respect.
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PMID:Tissue factor pathway inhibitor and P-selectin as markers of sepsis-induced non-overt disseminated intravascular coagulopathy. 1968 98

Sepsis is a systemic response to an infection that leads to a generalized inflammatory reaction. There is an intimate relationship between procoagulant and proinflammatory activities, and coagulation abnormalities are common in septic patients. Pharmaceutical studies have focused to the development of substances that act on coagulation abnormalities and on the link between coagulation and inflammation. Fructose-1,6-bisphosphate (FBP) is a high-energy glycolitic metabolite that in the past two decades has been shown therapeutic effects in great number of pathological situations, including sepsis. The aims of this study were to assess the effects of FBP on platelet aggregation in vitro and ex vivo in healthy and septic rats and evaluate the use of FBP as a treatment for thrombocytopenia and coagulation abnormalities in abdominal sepsis in rat. FBP inhibited platelet aggregation (P < 0.001) in vitro in healthy rats from the smallest dose tested, 2.5 mM, in a dose-dependent manner. The mean effective dose calculated was 10.6 mM. The highest dose tested, 40 mM, completely inhibited platelet aggregation (P < 0.001) induced by ADP. Platelet aggregation in plasma from septic rats was inhibited only with higher doses of FBP, starting from 20 mM (P < 0.001). The calculated mean effective dose was 19.3 mM. Ex vivo platelet aggregation in septic rats was significantly lower (P < 0.05) than healthy rats and the treatment with FBP, at the dose of 2 g/kg, diminished the platelet aggregation at the extension of 27% (P < 0.001), suggesting that FBP is a potent platelet aggregation inhibitor in vivo. Moreover, treatment with FBP 2 g/kg prevented thrombocytopenia (P < 0.001), prolongation of prothrombin and partial thromboplastin time (P < 0.001), but not fibrinogen, in septic rats. The most important findings in this study are that FBP is a potent platelet aggregation inhibitor, in vitro and ex vivo. It presents protective effects on coagulation abnormalities, which can represent a treatment against DIC. The mechanisms for these effects remain under investigation.
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PMID:Fructose-1,6-bisphosphate inhibits in vitro and ex vivo platelet aggregation induced by ADP and ameliorates coagulation alterations in experimental sepsis in rats. 1970 56

Coagulation abnormalities are common in severe pneumonia and sepsis, yet little is known about the presence of coagulopathy or its significance in patients with lesser illness severity. We examined coagulation abnormalities in 939 subjects hospitalized with community-acquired pneumonia (CAP) in 28 US hospitals, hypothesizing that abnormalities would increase with illness severity and poor outcomes. We measured plasma coagulation markers (D-dimer, plasminogen activator inhibitor [PAI], antithrombin, factor IX, and thrombin-antithrombin complex [TAT]) at the time of patient presentation to the emergency department and daily during the first wk of hospitalization. Day-1 clinical laboratory test results for international normalized ratio, activated partial thromboplastin time, and platelet count were recorded from the medical record. In our cohort, 32.5% of patients developed severe sepsis and 11.1% died by d 90. Day-1 coagulation abnormalities were common, especially for D-dimer (80.6%) and TAT (36.0%), and increased with illness severity and poor outcomes. However, abnormalities also occurred in those patients who never developed organ dysfunction and differences between groups were modest. The proportion of patients with abnormalities changed over time, yet the magnitude of change was small and not always in the direction of normality. Many patients remaining in the hospital continued to manifest coagulation abnormalities on d 7, especially for D-dimer (86.5%) and TAT (36.9%). In conclusion, coagulation abnormalities were common and persistent in CAP patients, even among the least ill. These findings underscore the complexity of the coagulation response to infection and may offer insights into coagulation-based therapeutics in clinical sepsis trials.
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PMID:Prevalence and significance of coagulation abnormalities in community-acquired pneumonia. 1975 44

The objective of our study was to examine the changes in coagulation parameters and inflammatory reaction over the course of 15 days in patients with severe sepsis. We tried to identify mechanisms by which sepsis-induced pathophysiological changes may influence the effectiveness of subcutaneously (SC) administered enoxaparin 40 mg once daily. A total of 16 patients (8 men, 8 women; age 35-83 years) meeting the inclusion criteria of severe sepsis were enrolled in this study. The follow-up was performed on days 1, 2, 3, 6, 9, 12, and 15 of hospitalization at the intensive care unit (ICU). Blood coagulation (activated partial thromboplastin time [aPTT], prothrombin time [PT], fibrinogen, antithrombin (AT), protein C [PC], D-dimer, fragment 1.2 [F1.2], factor Xa [FXa] inhibition) and inflammatory reactants (interleukin 6 [IL-6], C-reactive protein [CRP], orosomucoid, alpha-1-antitrypsin) were tested. The mean FXa inhibition was 0.17 (+ or - 0.17) IU/mL. The arbitrarily established range of FXa inhibition for prophylaxis, 0.2 to 0.4 IU/mL, was reached in 22 cases (20%), while in 74 cases (68%), it was below and in 13 cases (12%) above the aforementioned range. Factor Xa inhibition positively correlated with AT (r = .42; P < .001) and PC (r = .45; P < .001) activities. A negative correlation was found between the FXa inhibition and alpha-1-antitrypsin concentrations (r = -.33; P = .01) but only in the subgroup with alpha-1-antitrypsin concentrations > or = 2.2 g/L. We confirmed that in most patients with sepsis, the prophylaxis with enoxaparin did not lead to the required FXa inhibition. The inhibition of FXa by enoxaparin depends mainly on the AT and PC activities.
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PMID:FXa inhibition and coagulation changes during DVT prophylaxis by enoxaparin over the course of a 15-day follow-up in septic patients. 1985 May 87

Extracorporeal membrane oxygenation (ECMO) is a life-saving therapy for infants and children with cardiac and respiratory failure. However, thrombosis and hemorrhage are common complications. To determine clinical and laboratory predictors of thrombosis and hemorrhage resulting from ECMO, records and slides were reviewed from 29 consecutive autopsies from 2004 through 2008 of pediatric patients who received ECMO at our institution. Laboratory results, including prothrombin time, activated partial thromboplastin time, platelet count, fibrinogen level, and activated clotting time, were analyzed, as was heparin dosing. Thrombosis and hemorrhage were very common, with 1 or both seen in 86% of patients. Sixty-nine percent had thrombosis, and 52% had hemorrhage after ECMO initiation, including intracranial hemorrhage in 33% of the patients in whom brain examination was permitted. Hemorrhage and thrombosis coexisted in 31% of patients. Thrombosis was significantly more common in patients with congenital cardiac disease. Duration of ECMO therapy, being on ECMO at death, sepsis, and patient age and sex did not predict hemorrhage or thrombosis at autopsy. Laboratory tests were poor predictors of thrombosis and hemorrhage, with no correlation between these complications and prothrombin time, partial thromboplastin time, platelet count, fibrinogen level, activated clotting time, or heparin dose. In conclusion, thrombosis and hemorrhage continue to be frequent complications among patients who die during or after ECMO therapy. Patients with congenital cardiac disease appear especially susceptible to thrombosis on ECMO. Prothrombin time, partial thromboplastin time, platelet count, fibrinogen level, activated clotting time, and heparin dose are poor predictors of thrombosis or hemorrhage for pediatric patients who die after ECMO.
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PMID:Laboratory and clinical predictors of thrombosis and hemorrhage in 29 pediatric extracorporeal membrane oxygenation nonsurvivors. 2008 98


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