title: Activated protein C attenuates pulmonary coagulopathy in patients with acute respiratory distress syndrome.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  An infusion of rh-APC in patients with ARDS attenuates pulmonary coagulopathy and injury.
authors: Department of Intensive Care Medicine, VU University Medical Center Amsterdam, Amsterdam, The Netherlands. cornet@vumc.nl
authors: A D
authors: AD
authors: Cornet
authors: J J
authors: JJ
authors: Hofstra
authors: A P
authors: AP
authors: Vlaar
authors: P R
authors: PR
authors: Tuinman
authors: M
authors: M
authors: Levi
authors: A R
authors: AR
authors: Girbes
authors: M J
authors: MJ
authors: Schultz
authors: A B
authors: AB
authors: Groeneveld
authors: A
authors: A
authors: Beishuizen
mesh_terms: D001778:Blood Coagulation Disorders / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D001992:Bronchoalveolar Lavage Fluid; D005260:Female; D006801:Humans; D008171:Lung Diseases / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011486:Protein C / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012128:Respiratory Distress Syndrome / Q000097:blood / Q000150:complications*
chemical_list: D010919:Placebos; D011486:Protein C; D011994:Recombinant Proteins