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Randomized Controlled Trial
. 2013 May;11(5):894-901.
doi: 10.1111/jth.12179.

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

A D Cornet  1 , J J Hofstra, A P Vlaar, P R Tuinman, M Levi, A R Girbes, M J Schultz, A B Groeneveld, A Beishuizen
Affiliations
Randomized Controlled Trial

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

A D Cornet et al. J Thromb Haemost. 2013 May.

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.

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

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Figures

Figure 1
Figure 1
CONSORT diagram. ARDS, acute respiratory distress syndrome; rh-APC, recombinant human activated protein C; SCT, stem cell transplantation; plts, platetelets; NBL, non-directed bronchoalveolar lavage
Figure 2
Figure 2
Effect of recombinant human activated protein (rh-APC) administration on systemic levels of APC, thrombin–antithrombin complexes (TATc), plasminogen activator activity (PAA) and plasminogen activator inhibitor-1 (PAI-1). Differences in APC were significant on days 2–5 (P < 0.01). Differences in TATc, PAA and PAI-1 were significant on days 2–5 (P < 0.01) and day 7 (P < 0.05).
Figure 3
Figure 3
Effect of recombinant human activated protein (rh-APC) administration on levels of APC, thrombin–antithrombin complexes (TATc), antithrombin (AT), plasminogen activator activity (PAA), plasminogen activator inhibitor-1 (PAI-1) and soluble tissue factor (sTF) in non-directed bronchoalveolar lavage fluid. Differences in APC, PAA, PAI-1 and sTF were significant on days 2–4 (P < 0.01) and day 5 (P < 0.05). Differences in TATc were significant on days 2–5 (P < 0.01). There were no significant differences in AT.
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