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

Infection and inflammation and the coagulation system

Severe infection and inflammation almost invariably lead to hemostatic abnormalities, ranging from insignificant laboratory changes to severe disseminated intravascular coagulation (DIC). Systemic inflammation results in activation of coagulation, due to tissue factor-mediated thrombin generation, downregulation of physiological anticoagulant mechanisms, and inhibition of fibrinolysis. Proinflammatory cytokines play a central role in the differential effects on the coagulation and fibrinolysis pathways. Vice-versa, activation of the coagulation system may importantly affect inflammatory responses by direct and indirect mechanisms. Apart from the general coagulation response to inflammation associated with severe infection, specific infections may cause distinct features, such as hemorrhagic fever or thrombotic microangiopathy. The relevance of the cross-talk between inflammation and coagulation is underlined by the promising results in the treatment of severe systemic infection with modulators of coagulation and inflammation. (C) 2003 European Society of Cardiology. Published by Elsevier B.V. All rights reserve

Chlamydia pneumoniae infections in mouse models: relevance for atherosclerosis research

Mouse models have been frequently used in the study of Chlamydia pneumoniae (also known as Chlamydophila pneumoniae) infections. This gram-negative obligate intracellular bacterium causes respiratory infections, followed by dissemination of the bacterium to various organs throughout the body, including cardiovascular tissues, supporting the current hypothesis of a relationship between C pneunioniae and atherosclerosis. Recently, clinical trials evaluated the effect of antichlamydial antibiotics on secondary cardiovascular events. Although small studies showed some effect, the large WIZARD study did not confirm these results, and the role of antichlamydial antibiotics in prevention of secondary events was questioned. To address these issues, data obtained from mouse models were systematically reviewed here. C. pneunioniae infections showed atherogenic properties in mice that were reproducible and confirmed by different research groups. However, antibiotic therapy was of limited value in these mouse models. Antibiotic therapy effectively cleared the acute infection, but did not influence the atherogenic properties of C pneumoniae unless the therapy was started early during the acute infection. The results summarized here may help to better understand the results of the clinical antibiotic trials. (C) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserve

Infections and endothelial cells

Systemic infection by various pathogens interacts with the endothelium and may result in altered coagulation, vasculitis and atherosclerosis. Endothelium plays a role in the initiation and regulation of both coagulation and fibrinolysis. Exposure of endothelial cells may lead to rapid activation of coagulation via tissue factor (TF) expression and the loss of anticoagulant properties by impairment of antithrombin III, TF pathway inhibitor (TFPI) and the protein C system. Endothelial-derived plasminogen activator inhibitor (PAI) is essential for the regulation of fibrinolysis and impaired endothelial function leads to imbalance in fibrinolysis, resulting in a procoagulant state. The interaction between inflammation and coagulation, soluble adhesion molecules and circulation endothelial cells is important in the pathogenesis of an unbalanced haemostatic system. Rather than being a unidirectional relationship, the interaction between inflammation and coagulation appears to be significant. In the crosstalk, the endothelium is playing a pivotal role. (C) 2003 European Society of Cardiology. Published by Elsevier B.V. All rights reserve

Serum levels of type II secretory phospholipase A2 and the risk of future coronary artery disease in apparently healthy men and women - The EPIC-Norfolk Prospective Population study

Objectives - To study the prospective relationship between serum levels of type II secretory phospholipase A2 (sPLA2) and the risk of future coronary artery disease ( CAD) in apparently healthy men and women. Methods and Results - We conducted a prospective nested case-control study among apparently healthy men and women aged 45 to 79 years. Cases ( n = 1105) were people in whom fatal or nonfatal CAD developed during follow-up. Controls ( n = 2209) were matched by age, sex, and enrollment time. sPLA2 levels were significantly higher in cases than controls ( 9.5 ng/mL; interquartile range [IQR], 6.4 to 14.8 versus 8.3 ng/mL; IQR, 5.8 to 12.6; P <0.0001). sPLA2 plasma levels significantly correlated with age, body mass index, systolic blood pressure, high-density lipoprotein (HDL) cholesterol levels, and C-reactive protein ( CRP) levels. Taking into account matching for sex and age and adjusting for body mass index, smoking, diabetes, systolic blood pressure, low-density lipoprotein cholesterol, HDL cholesterol, and CRP levels, the risk of future CAD was 1.34 ( 1.02 to 1.71; P = 0.02) for people in the highest sPLA2 quartile, compared with those in the lowest ( P for linearity = 0.03). Conclusion - Elevated levels of sPLA2 were associated with an increased risk of future CAD in apparently healthy individuals. The magnitude of the association was similar to that observed between CRP and CAD risk, and both associations were independen

Effects on coagulation and fibrinolysis induced by influenza in mice with a reduced capacity to generate activated protein C and a deficiency in plasminogen activator inhibitor type 1

Influenza infections increase the risk of diseases associated with a prothrombotic state, such as venous thrombosis and atherothrombotic diseases. However, it is unclear whether influenza leads to a prothrombotic state in vivo. To determine whether influenza activates coagulation, we measured coagulation and fibrinolysis in influenza-infected C57BL/6 mice. We found that influenza increased thrombin generation, fibrin deposition, and fibrinolysis. In addition, we used various anti- and prothrombotic models to study pathways involved in the influenza-induced prothrombotic state. A reduced capacity to generate activated protein C in TM(pro/pro) mice increased thrombin generation and fibrinolysis, whereas treatment with heparin decreased thrombin generation in influenza-infected C57Bl/6 mice. Thrombin generation was not changed in hyperfibrinolytic mice, deficient in plasminogen activator inhibitor type-1 (PAI-1(-/-)); however, increased fibrin degradation was seen. Treatment with tranexamic acid reduced fibrinolysis, but thrombin generation was unchanged. We conclude that influenza infection generates thrombin, increased by reduced levels of protein C and decreased by heparin. The fibrinolytic system appears not to be important for thrombin generation. These findings suggest that influenza leads to a prothrombotic state by coagulation activation. Heparin treatment reduces the influenza induced prothrombotic stat