Single Low Dose of Human Recombinant Antithrombin (Atryn®) Has no Impact on Endotoxin-induced Disseminated Intravascular Coagulation: An Experimental Randomized Open Label Controlled Study


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Abstract

Background:Antithrombin III physiological levels are decreased during septic shock, and supplementation therapy could therefore be beneficial.Objective:We hypothesized that the use of recombinant human antithrombin could reduce Disseminated Intravascular Coagulation (DIC) occurrence.Methods:We conducted a randomized open label controlled experimental study. Ten female “Large White” pigs were challenged with intravenous infusion of E.coli endotoxin. Two groups of five pigs were randomly assigned to receive either recombinant human antithrombin 100 U/kg over 30 minutes [ATryn group] or 0.9% saline [control group]. Antithrombin III levels, coagulation, hemostasis, inflammation parameters, hemodynamics and microcirculatory parameters were measured over a 5-h period. Immediately after euthanasia, kidneys were withdrawn for histology evaluation. Statistical analysis was performed with non-parametric tests and Dunn's test for multiple comparisons.Results:AT III activity was significantly higher in the ATryn group than in the control group from 60% (213 [203–223] vs 104% [98–115], p = 0.008, respectively) to 300 minutes (115% [95–124] vs 79% [67–93], p = 0.03). Recombinant human antithrombin supplementation had no impact on hemodynamics, microcirculatory parameters and sequential changes of coagulation parameters (platelet count, fibrinogen level, thrombin-antithrombin complexes and von Willebrand factor). Interleukin 6 and Tumor Necrosis Factor alpha values were statistically the same for both groups throughout the study. Percentage of thrombosed glomeruli and percentage of thrombosed capillary in glomerulus were not significantly different between both groups.Conclusions:In our model of endotoxic shock, a single low dose of recombinant human Antithrombin did not prevent Disseminated Intravascular Coagulation occurrence, severity, inflammatory profile or hemodynamic alterations.

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