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

J Thromb Haemost. 2013 May;11(5):894-901. doi: 10.1111/jth.12179.


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.

Conclusion: An infusion of rh-APC in patients with ARDS attenuates pulmonary coagulopathy and injury.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Coagulation Disorders / blood
  • Blood Coagulation Disorders / drug therapy*
  • Blood Coagulation Disorders / etiology
  • Bronchoalveolar Lavage Fluid
  • Female
  • Humans
  • Lung Diseases / blood
  • Lung Diseases / drug therapy*
  • Lung Diseases / etiology
  • Male
  • Middle Aged
  • Placebos
  • Protein C / therapeutic use*
  • Recombinant Proteins / therapeutic use
  • Respiratory Distress Syndrome / blood
  • Respiratory Distress Syndrome / complications*


  • Placebos
  • Protein C
  • Recombinant Proteins