Activated protein C attenuates pulmonary coagulopathy in patients with acute respiratory distress syndrome. Issue 5 (15th May 2013)

• Record Type: Journal Article
• Authors: Cornet, A. D.; Hofstra, J. J.; Vlaar, A. P.; Tuinman, P. R.; Levi, M.; Girbes, A. R.; Schultz, M. J.; Groeneveld, A. B.; Beishuizen, A.
• Is Part Of: Journal of thrombosis and haemostasis. Volume 11:Issue 5(2013)
• Page Start: 894
• Page End: 901
• Publication Date: 2013-05-15
• Subjects: Thrombosis -- Periodicals; Hemostasis -- Periodicals; Blood coagulation disorders -- Periodicals; 616.1
• DOI: 10.1111/jth.12179
• Languages: English
• ISSNs: 1538-7933

Abstract

<abstract abstract-type="main" id="jth12179-abs-0001"> <title>Summary</title> <sec id="jth12179-sec-0001" sec-type="section"> <title>Objective</title> <p>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.</p> </sec> <sec id="jth12179-sec-0002" sec-type="section"> <title>Methods</title> <p>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<sup>−1</sup> h<sup>−1</sup> for 96 h) with placebo. Patients with sepsis or septic shock were excluded.</p> </sec> <sec id="jth12179-sec-0003" sec-type="section"> <title>Results</title> <p>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 (<italic>P</italic> = 0.001), as well as higher APC levels in NBLF up to day 5 after the start of the infusion (<italic>P</italic> = 0.028). An infusion of rh‐APC was associated with lower levels of thrombin–antithrombin complexes (<italic>P</italic> = 0.009) and soluble tissue factor (<italic>P</italic> = 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 (<italic>P</italic> = 0.01), presumably as a result of lower NBLF levels of plasminogen activator inhibitor 1, (<italic>P</italic> = 0.01). The rh‐APC infusion decreased the lung injury score (<italic>P</italic> = 0.005) and simplified the acute physiology score (<italic>P</italic> = 0.013) on day 5, when compared with baseline. The rh‐APC infusion was not associated with bleeding complications.</p> </sec> <sec id="jth12179-sec-0004" sec-type="section"> <title>Conclusion</title> <p>An infusion of rh‐APC in patients with ARDS attenuates pulmonary coagulopathy and injury.</p> </sec> </abstract>