• Goda Choi, Jorrit-Jan H Hofstra, Joris J T H Roelofs, Anita W Rijneveld, Paul Bresser, Jaring S van der Zee, Sandrine Florquin, Tom van der Poll, Marcel Levi, and Marcus J Schultz.
• Department of Intensive Care Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. godachoi@mail.com
• Crit. Care Med. 2008 Jan 1;36(1):204-10.

ObjectiveAlveolar fibrin deposition is a hallmark of pneumonia. It has been proposed that natural inhibitors of coagulation, including activated protein C, antithrombin, and tissue factor pathway inhibitor, exert lung-protective effects via anticoagulant and possibly anti-inflammatory pathways. We investigated the role of these natural anticoagulants in Streptococcus pneumoniae pneumonia.DesignA controlled in vivo laboratory study.SettingResearch laboratory of a university hospital.SubjectsTotal of 98 male Sprague-Dawley rats.InterventionsRats were challenged intratracheally with S. pneumoniae (serotype 3, 10(6) colony forming units), inducing pneumonia. Rats were randomized to intravenous treatment with normal saline, activated protein C, antithrombin, tissue factor pathway inhibitor, heparin, or tissue-type plasminogen activator.Measurements And Main ResultsRats infected with S. pneumoniae had increased thrombin-antithrombin complexes in bronchoalveolar lavage fluid, with decreased levels of antithrombin activity and fibrin degradation products. Administration of activated protein C, antithrombin, and tissue factor pathway inhibitor significantly limited these procoagulant changes. Furthermore, antithrombin treatment resulted in less bacterial outgrowth of S. pneumoniae and less histopathologic damage in lungs.ConclusionsAnticoagulant treatment attenuates pulmonary coagulopathy during S. pneumoniae pneumonia. Antithrombin seems to exert significant lung-protective effects in pneumococcal pneumonia in rats.

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