• Florry E van den Boogaard, Marcel Schouten, Sacha F de Stoppelaar, Joris J T H Roelofs, Xanthe Brands, Marcus J Schultz, Cornelis van't Veer, and Tom van der Poll.
• 1Center for Experimental and Molecular Medicine (CEMM), Academic Medical Center, Amsterdam, The Netherlands. 2Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, Amsterdam, The Netherlands. 3Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands. 4Department of Intensive Care Medicine, Academic Medical Center, Amsterdam, The Netherlands. 5Laboratory of Experimental Intensive Care and Anesthesiology (LEICA), Academic Medical Center, Amsterdam, The Netherlands. 6Division of Infectious Diseases, Academic Medical Center, Amsterdam, The Netherlands.
• Crit. Care Med.. 2015 Mar 1;43(3):e75-83.

ObjectivesStreptococcus pneumoniae is the most common causative pathogen in community-acquired pneumonia. In patients, thrombocytopenia is correlated with an adverse outcome of pneumonia. Platelets can modulate the host response to infection in several ways, that is, by facilitating clot formation, production of antimicrobial proteins, and interaction with neutrophils. We studied the effect of thrombocytopenia during murine pneumococcal pneumonia.DesignAnimal study.SettingUniversity research laboratory.SubjectsMice.InterventionsPneumonia was induced by intranasal inoculation of S. pneumoniae. Platelets were depleted by anti-mouse thrombocyte serum; controls received nonimmunogenic serum. In separate studies, mice were treated with the platelet P2Y12 receptor inhibitor clopidogrel or placebo.Measurements And Main ResultsThrombocytopenic mice (platelet counts < 1% of uninfected controls) showed a reduced survival during pneumococcal pneumonia (27% vs 75% among controls; p = 0.003), which was associated with higher bacterial loads in lungs, spleen, and blood. Thrombocytopenic mice showed enhanced coagulation activation (thrombin-antithrombin complexes) in plasma. Proinflammatory cytokine levels were higher in plasma but not in lungs of thrombocytopenic mice. Although clopidogrel treatment strongly prolonged the bleeding time, it did not impact on bacterial loads during pneumococcal pneumonia.ConclusionsPlatelets play a protective role during pneumococcal pneumonia independent of their aggregation.

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