Endogenous plasma activated protein C levels and the effect of enoxaparin and drotrecogin alfa (activated) on markers of coagulation activation and fibrinolysis in pulmonary embolism.
Author(s): Dempfle CE, Elmas E, Link A, Suvajac N, Liebe V, Janes J, Borggrefe M
Affiliation(s): I Department of Medicine, University Medical Center Mannheim, Theodor Kutzer Ufer, Mannheim D-68167, Germany. email@example.com
Publication date & source: 2011, Crit Care., 15(1):R23. Epub 2011 Jan 17.
Publication type: Clinical Trial, Phase II; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
INTRODUCTION: There are no published data on the status of endogenous activated protein C (APC) in pulmonary embolism (PE), and no data on the effect of drotrecogin alfa (activated) (DAA) given in addition to therapeutic dose enoxaparin. METHODS: In this double-blind clinical trial, 47 patients with computed tomography (CT)-confirmed acute submassive PE treated with 1 mg/kg body weight of enoxaparin twice daily were randomized to groups receiving a 12-hour intravenous infusion of 6, 12, 18, or 24 mug/kg/hour of DAA or a placebo. Blood samples were drawn before starting DAA infusion, after 4, 8 and 12 hours (at the end of the infusion period), and on treatment days 2, 3, 4, 5 and 6. RESULTS: Initial endogenous plasma activated protein C (APC) levels were 0.36 +/- 0.48 ng/ml (<0.10 to 1.72 ng/ml) and remained in the same range in the placebo group. APC levels in patients treated with DAA were 13.67 +/- 3.57 ng/ml, 32.71 +/- 8.76 ng/ml, 36.13 +/- 7.60 ng/ml, and 51.79 +/- 15.84 ng/ml in patients treated with 6, 12, 18, and 24 mug/kg/hour DAA, respectively. In patients with a D-dimer level >4 mg/L indicating a high level of acute fibrin formation and dissolution, DAA infusion resulted in a more rapid drop in soluble fibrin, D-dimer, and fibrinogen/fibrin degradation products (FDP) levels, compared to enoxaparin alone. There was a parallel decline of soluble fibrin, D-dimer, FDP, and plasmin-plasmin inhibitor complex (PPIC) in response to treatment with enoxaparin +/- DAA, with no evidence of a systemic profibrinolytic effect of the treatment. CONCLUSIONS: In patients with acute submassive PE endogenous APC levels are low. DAA infusion enhances the inhibition of fibrin formation. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00191724.