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

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 mcgkg(-1) h(-1) for 96h) 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 4days (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.