Both authors contributed equally.
Activated protein C attenuates pulmonary coagulopathy in patients with acute respiratory distress syndrome
Version of Record online: 15 MAY 2013
© 2013 International Society on Thrombosis and Haemostasis
Journal of Thrombosis and Haemostasis
Volume 11, Issue 5, pages 894–901, May 2013
How to Cite
Activated protein C attenuates pulmonary coagulopathy in patients with acute respiratory distress syndrome. J Thromb Haemost 2013; 11: 894–901., , , , , , , , .
- Issue online: 15 MAY 2013
- Version of Record online: 15 MAY 2013
- Accepted manuscript online: 25 FEB 2013 05:49AM EST
- Manuscript Accepted: 15 FEB 2013
- Manuscript Received: 3 DEC 2012
- ARDS ;
- critically ill;
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.