• A D Cornet, J J Hofstra, A P Vlaar, P R Tuinman, M Levi, A R Girbes, M J Schultz, A B Groeneveld, and A Beishuizen.
• Department of Intensive Care Medicine, VU University Medical Center Amsterdam, Amsterdam, The Netherlands. cornet@vumc.nl
• J. Thromb. Haemost. 2013 May 1; 11 (5): 894-901.

ObjectiveAcute respiratory distress syndrome (ARDS) frequently complicates critical illness. We hypothesized that an infusion of recombinant human activated protein C (rh-APC), a natural anticoagulant, would attenuate pulmonary coagulopathy and injury.MethodsIn this sub study of a multicenter open-label randomized controlled trial of patients with ARDS, we compared an intravenous (i.v.) infusion of rh-APC (24 mcg kg(-1)  h(-1) for 96 h) with placebo. Patients with sepsis or septic shock were excluded.ResultsIn 27 patients serial non-directed bronchoalveolar lavage fluid (NBLF) samples were obtained: 16 patients were treated with rh-APC and 11 patients with placebo. The rh-APC infusion was associated with higher APC levels in plasma during the infusion period of 4 days (P = 0.001), as well as higher APC levels in NBLF up to day 5 after the start of the infusion (P = 0.028). An infusion of rh-APC was associated with lower levels of thrombin-antithrombin complexes (P = 0.009) and soluble tissue factor (P = 0.011) in NBLF, compared with treatment with placebo. An infusion of rh-APC affected fibrinolysis, as plasminogen activator activity levels in NBLF were higher in the patients treated with rh-APC (P = 0.01), presumably as a result of lower NBLF levels of plasminogen activator inhibitor 1, (P = 0.01). The rh-APC infusion decreased the lung injury score (P = 0.005) and simplified the acute physiology score (P = 0.013) on day 5, when compared with baseline. The rh-APC infusion was not associated with bleeding complications.ConclusionAn infusion of rh-APC in patients with ARDS attenuates pulmonary coagulopathy and injury.© 2013 International Society on Thrombosis and Haemostasis.

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