Single Low Dose of Human Recombinant ...
Document type :
Article dans une revue scientifique: Article original
PMID :
Permalink :
Title :
Single Low Dose of Human Recombinant Antithrombin (Atryn®) Has no Impact on Endotoxin-induced Disseminated Intravascular Coagulation: An Experimental Randomized Open Label Controlled Study
Author(s) :
Duburcq, Thomas [Auteur]
Recherche translationnelle sur le diabète - U 1190 [RTD]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Durand, Arthur [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Tournoys, Antoine [Auteur]
Pôle de Biologie Pathologie Génétique [CHU Lille]
Gnemmi, Viviane [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc) - U1172
Pôle de Biologie Pathologie Génétique [CHU Lille]
Bonner, Caroline [Auteur]
Recherche translationnelle sur le diabète (RTD) - U1190
Gmyr, Valery [Auteur]
Recherche translationnelle sur le diabète (RTD) - U1190
Hubert, Thomas [Auteur]
Recherche translationnelle sur le diabète (RTD) - U1190
Pattou, Francois [Auteur]
Institut Pasteur de Lille
Recherche translationnelle sur le diabète (RTD) - U1190
Jourdain, Mercedes [Auteur]
Pôle de Biologie Pathologie Génétique [CHU Lille]
Recherche translationnelle sur le diabète (RTD) - U1190
Recherche translationnelle sur le diabète - U 1190 [RTD]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Durand, Arthur [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Tournoys, Antoine [Auteur]
Pôle de Biologie Pathologie Génétique [CHU Lille]
Gnemmi, Viviane [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc) - U1172
Pôle de Biologie Pathologie Génétique [CHU Lille]
Bonner, Caroline [Auteur]
Recherche translationnelle sur le diabète (RTD) - U1190
Gmyr, Valery [Auteur]
Recherche translationnelle sur le diabète (RTD) - U1190
Hubert, Thomas [Auteur]
Recherche translationnelle sur le diabète (RTD) - U1190
Pattou, Francois [Auteur]
Institut Pasteur de Lille
Recherche translationnelle sur le diabète (RTD) - U1190
Jourdain, Mercedes [Auteur]
Pôle de Biologie Pathologie Génétique [CHU Lille]
Recherche translationnelle sur le diabète (RTD) - U1190
Journal title :
Shock
Volume number :
52
Pages :
e60-e67
Publisher :
Wolters Kluwer
Publication date :
2019-10
ISSN :
1540-0514
English keyword(s) :
Antithrombin
disseminated intravascular coagulation
hemodynamics
inflammation
microcirculation
septic shock
AT
Antithrombin
hpAT
human pooled antithrombin
rhAT
human recombinant antithrobin
DIC
Disseminated Intravascular Coagulation
MAP
Mean Arterial Pressure
TAT
Thrombin-Anti-Thrombin complex
vWF
von Willebrand Factor
TNFα
Tumor Necrosis Factor alpha
IL-6
Interleukin 6
E.coli
Escherichia coli
LPS
Lipopolysaccharide
disseminated intravascular coagulation
hemodynamics
inflammation
microcirculation
septic shock
AT
Antithrombin
hpAT
human pooled antithrombin
rhAT
human recombinant antithrobin
DIC
Disseminated Intravascular Coagulation
MAP
Mean Arterial Pressure
TAT
Thrombin-Anti-Thrombin complex
vWF
von Willebrand Factor
TNFα
Tumor Necrosis Factor alpha
IL-6
Interleukin 6
E.coli
Escherichia coli
LPS
Lipopolysaccharide
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [en]
Background:
Antithrombin (AT) III physiological levels are decreased during septic shock and supplementation therapy could therefore be beneficial.
Objective:
We hypothesized that the use of recombinant human AT ...
Show more >Background: Antithrombin (AT) III physiological levels are decreased during septic shock and supplementation therapy could therefore be beneficial. Objective: We hypothesized that the use of recombinant human AT 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 i.v. infusion of Escherichia coli endotoxin. Two groups of 5 pigs were randomly assigned to receive either recombinant human AT 100 U/kg over 30 min (ATryn group) or 0.9% saline (control group). AT 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 nonparametric 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 min (115% [95–124] vs. 79% [67–93], P = 0.03). Recombinant human AT supplementation had no impact on hemodynamics, microcirculatory parameters, and sequential changes of coagulation parameters (platelet count, fibrinogen level, thrombin–AT complexes, and von Willebrand factor). Interleukin 6 and tumor necrosis factor α 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 AT did not prevent DIC occurrence, severity, inflammatory profile, or hemodynamic alterations.Show less >
Show more >Background: Antithrombin (AT) III physiological levels are decreased during septic shock and supplementation therapy could therefore be beneficial. Objective: We hypothesized that the use of recombinant human AT 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 i.v. infusion of Escherichia coli endotoxin. Two groups of 5 pigs were randomly assigned to receive either recombinant human AT 100 U/kg over 30 min (ATryn group) or 0.9% saline (control group). AT 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 nonparametric 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 min (115% [95–124] vs. 79% [67–93], P = 0.03). Recombinant human AT supplementation had no impact on hemodynamics, microcirculatory parameters, and sequential changes of coagulation parameters (platelet count, fibrinogen level, thrombin–AT complexes, and von Willebrand factor). Interleukin 6 and tumor necrosis factor α 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 AT did not prevent DIC occurrence, severity, inflammatory profile, or hemodynamic alterations.Show less >
Language :
Anglais
Audience :
Internationale
Popular science :
Non
Administrative institution(s) :
Université de Lille
Inserm
CHU Lille
Inserm
CHU Lille
Collections :
Submission date :
2024-01-19T23:57:04Z
2024-09-18T09:29:26Z
2024-09-18T09:29:26Z