Markers of inflammation and coagulation indicate a prothrombotic state in HIV-infected patients with long-term use of antiretroviral therapy with or without abacavir

Background: Abacavir (ABC) treatment has been associated with an increased incidence of myocardial infarction. The pathophysiological mechanism is unknown. In this study markers of inflammation and coagulation in HIV-infected patients using antiretroviral therapy with or without ABC were examined to pinpoint a pathogenic mechanism. Given the important role of high sensitivity C-reactive protein (hsCRP) levels in predicting cardiovascular risk, patient groups were also analyzed according to hsCRP levels.Method

Influenza infection and risk of acute pulmonary embolism

<p>Abstract</p> <p>Background</p> <p>Influenza infections have been associated with procoagulant changes. Whether influenza infections lead to an increased risk of pulmonary embolism remains to be established.</p> <p>Methods</p> <p>We conducted a nested case control study in a large cohort of patients with a clinical suspicion of having pulmonary embolism. Blood samples were collected to investigate the presence of influenza A and B by complement fixation assay (CFA). We compared case patients, in whom pulmonary embolism was proven (n = 102), to controls, in whom pulmonary embolism was excluded (n = 395). Furthermore, we compared symptoms of influenza-like illness in both patient groups 2 weeks prior to inclusion in the study, using the influenza-like illness (ILI) score, which is based on a questionnaire. We calculated the risk of pulmonary embolism associated with influenza infection.</p> <p>Results</p> <p>The percentage of patients with influenza A was higher in the control group compared to the case group (4.3% versus 1.0%, respectively, odds ratio 0.22; 95% CI: 0.03–1.72). Influenza B was not detectable in any of the cases and was found in 3 of the 395 controls (0.8%). The ILI score was positive in 24% of the cases and 25% in the control persons (odds ratio 1.16, 95% CI: 0.67–2.01). We did not observe an association between the ILI score and proven influenza infection.</p> <p>Conclusion</p> <p>In this clinical study, influenza infection was not associated with an increased risk of acute pulmonary embolism. The ILI score is non-specific in this clinical setting.</p

Risk Factors for Mortality in Dengue Shock Syndrome (DSS)

Background: Dengue shock syndrome (DSS) is the most severe form of dengue hemorrhagic fever (DHF) and has a high mortality. There are two major pathological changes in DHF determining the severity of disease, plasma leakage and bleeding. Cytokines released during the immune response to dengue virus have been thought to be mediators of the process. Methods: The study involved 50 children with DSS, of whom 13 (26%) died. We investigated which clinical signs and laboratory findings are related to mortality. Results: We found that gastrointestinal bleeding and bilateral pleural effusion were significantly more frequent in non-survivors than in survivors (p<0.02 and p=0.0006, respectively). Also, mean admission levels of thrombin-antithrombin complexes (TATc) and plasminogen activator inhibitor type 1 (PAI-1), activation markers of coagulation and fibrinolysis, respectively, were significantly higher in non-survivors (p=0.004 and p=0.0006, respectively). In regression analysis, bilateral pleural effusion and admission levels of TATc were significantly associated with mortality (p=0.007 and p=0.048, respectively). Conclusions: Our data provide evidence for a relationship of mortality with pleural effusion, a marker of plasma leakage, and coagulation activation, both characteristic pathological changes in dengue shock syndrome

Effect of Puumala hantavirus infection on Human Umbilical Vein Endothelial Cell hemostatic function: platelet interactions, increased tissue factor expression and fibrinolysis regulator release

Puumala virus (PUUV) infection causes over 5000 cases of hemorrhagic fever in Europe annually and can influence the hemostatic balance extensively. Infection might lead to hemorrhage, while a recent study showed an increased risk of myocardial infarction during or shortly after PUUV infection. The mechanism by which this hantavirus influences the coagulation system remains unknown. Therefore we aimed to elucidate mechanisms explaining alterations seen in primary and secondary hemostasis during PUUV infection. By using low passage PUUV isolates to infect primary human umbilical vein endothelial cells (HUVECs) we were able to show alterations in the regulation of primary- and secondary hemostasis and in the release of fibrinolysis regulators. Our main finding was an activation of secondary hemostasis due to increased tissue factor expression leading to increased thrombin generation in a functional assay. Furthermore, we showed that during infection platelets adhered to HUVECs and subsequently specifically to PUUV virus particles. Infection of HUVECs with PUUV did not result in increased von Willebrand factor while they produced more plasminogen activator inhibitor type-1 (PAI-1) compared to controls. The PAI-1 produced in this model formed complexes with vitronectin. This is the first report that reveals a potential mechanism behind the pro-coagulant changes in PUUV patients, which could be the result of increased thrombin generation due to an increased tissue factor expression on endothelial cells during infection. Furthermore, we provide insight into the contribution of endothelial cell responses regarding hemostasis in PUUV pathogenesis

MEDIA MEDIKA INDONESIANA Risk Factors for Mortality in Dengue Shock Syndrome (DSS)

ABSTRACT respectively). Also, mean admission levels of thrombin-antithrombin complexes (TATc) and plasminogen activator inhibitor type 1 (PAI-1), activation markers of coagulation and fibrinolysis, respectively, were significantly higher in . In regression analysis, bilateral pleural effusion and admission levels of TATc were significantly associated with mortality (p=0.007 and p=0.048, respectively). Conclusions: Our data provide evidence for a relationship of mortality with pleural effusion, a marker of plasma leakage, and coagulation activation, both characteristic pathological changes in dengue shock syndrome

Microbial Translocation Is Associated with Extensive Immune Activation in Dengue Virus Infected Patients with Severe Disease

Background: Severe dengue virus (DENV) disease is associated with extensive immune activation, characterized by a cytokine storm. Previously, elevated lipopolysaccharide (LPS) levels in dengue were found to correlate with clinical disease severity. In the present cross-sectional study we identified markers of microbial translocation and immune activation, which are associated with severe manifestations of DENV infection. Methods: Serum samples from DENV-infected patients were collected during the outbreak in 2010 in the State of Sao Paulo, Brazil. Levels of LPS, lipopolysaccharide binding protein (LBP), soluble CD14 (sCD14) and IgM and IgG endotoxin core antibodies were determined by ELISA. Thirty cytokines were quantified using a multiplex luminex system. Patients were classified according to the 2009 WHO classification and the occurrence of plasma leakage/shock and hemorrhage. Moreover, a (non-supervised) clus Results: Cluster analysis indicated that LPS levels were significantly increased in patients with a profound pro-inflammatory cytokine profile. LBP and sCD14 showed significantly increased levels in patients with severe disease in the clinical classification and in patients with severe inflammation in the cluster analysis. With both the clinical classification and the cluster analysis, levels of IL-6, IL-8, sIL-2R, MCP-1, RANTES, HGF, G-CSF and EGF were associated with severe disease. Conclusions: The present study provides evidence that both microbial translocation and extensive immune activation occur during severe DENV infection and may play an important role in the pathogenesis