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Activation of coagulation and inhibition of fibrinolysis in the human lung on bronchial instillation of lipoteichoic acid and lipopolysaccharide

Activation of coagulation and inhibition of fibrinolysis in the human lung on bronchial instillation of lipoteichoic acid and lipopolysaccharide

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HOOGERWERF, Jacobien J., Alex F. DE VOS, Marcel LEVI, Paul BRESSER, Jaring S. VAN DER ZEE, Christian DRAING, Sonja von AULOCK, Tom van der POLL, 2009. Activation of coagulation and inhibition of fibrinolysis in the human lung on bronchial instillation of lipoteichoic acid and lipopolysaccharide. In: Critical Care Medicine. 37(2), pp. 619-625. ISSN 0090-3493. eISSN 1530-0293

@article{Hoogerwerf2009Activ-1121, title={Activation of coagulation and inhibition of fibrinolysis in the human lung on bronchial instillation of lipoteichoic acid and lipopolysaccharide}, year={2009}, doi={10.1097/CCM.0b013e31819584f9}, number={2}, volume={37}, issn={0090-3493}, journal={Critical Care Medicine}, pages={619--625}, author={Hoogerwerf, Jacobien J. and De Vos, Alex F. and Levi, Marcel and Bresser, Paul and Van der Zee, Jaring S. and Draing, Christian and Aulock, Sonja von and Poll, Tom van der} }

Van der Zee, Jaring S. 2009 Bresser, Paul Objective: Pneumonia is characterized by an acute inflammatory response in the lung, which is frequently associated with changes in coagulation and fibrinolysis in the bronchoalveolar space. Here, we compared the effects of lipoteichoic acid (LTA), a major cell wall component of Gram-positive bacteria, and lipopolysaccharide (LPS), in the human bronchoalveolar space.<br />Design: Controlled in vivo volunteer study.<br />Setting: Clinical research unit.<br />Subjects: Twenty-three healthy nonsmoking male volunteers.<br />Interventions: Sterile saline was instilled into a lung subsegment followed by bronchoscopic instillation of either LTA (Staphylococcus aureus, at a dose of 4, 20, or 100 ng/kg body weight) or LPS (Escherichia coli, 4 ng/kg body weight) into the contralateral lung. Bronchoalveolar lavage fluid was obtained 6 hours thereafter.<br />Measurements and Main Results: Bronchial instillation of LTA- or LPS-activated bronchoalveolar coagulation, as reflected by increases in the levels of thrombin-antithrombin complexes, d-dimer, and soluble tissue factor. Concurrently, LTA and LPS inhibited anticoagulant mechanisms, as indicated by reductions in antithrombin, Protein C, and Activated Protein C concentrations together with elevated levels of soluble thrombomodulin. Both LTA and LPS administration was associated with an inhibition of pulmonary fibrinolysis, as measured by a reduction in plasminogen activator activity and elevated levels of plasminogen activator inhibitor type I.<br />Conclusions: This study is the first to describe the effects of LTA on hemostasis in humans, demonstrating that LTA induces similar changes in the human bronchoalveolar space as LPS, characterized by activation of coagulation with concurrent inhibition of anticoagulant and fibrinolytic pathways. Levi, Marcel Draing, Christian Aulock, Sonja von Poll, Tom van der Bresser, Paul Hoogerwerf, Jacobien J. deposit-license De Vos, Alex F. Levi, Marcel Publ. in: Critical Care Medicine 37 (2009), 2, pp. 619-625 Aulock, Sonja von 2011-03-23T09:06:17Z Van der Zee, Jaring S. De Vos, Alex F. 2011-03-23T09:06:17Z Draing, Christian eng Activation of coagulation and inhibition of fibrinolysis in the human lung on bronchial instillation of lipoteichoic acid and lipopolysaccharide Hoogerwerf, Jacobien J. Poll, Tom van der

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