Activated protein C attenuates pulmonary coagulopathy in patients with acute respiratory distress syndrome

A. D. Cornet, J. J. Hofstra, A. P. Vlaar, P. R. Tuinman, M. [=Marcel M.] Levi, A. R. Girbes, M. J. Schultz, A. B. Groeneveld, A. Beishuizen

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Abstract

Acute 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. In 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. In 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. An infusion of rh-APC in patients with ARDS attenuates pulmonary coagulopathy and injury
Original languageEnglish
Pages (from-to)894-901
JournalJournal of thrombosis and haemostasis
Volume11
Issue number5
DOIs
Publication statusPublished - 2013

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