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]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Recherche translationnelle sur le diabète - U 1190 [RTD]
Durand, Arthur [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Tournoys, Antoine [Auteur]
Pôle de Biologie Pathologie Génétique [CHU Lille]
Gnemmi, Viviane [Auteur]
Pôle de Biologie Pathologie Génétique [CHU Lille]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc) - U1172
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]
Recherche translationnelle sur le diabète (RTD) - U1190
Institut Pasteur de Lille
Jourdain, Mercedes [Auteur]
Recherche translationnelle sur le diabète (RTD) - U1190
Pôle de Biologie Pathologie Génétique [CHU Lille]

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

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 >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Recherche translationnelle sur le diabète (RTD) - U1190

Submission date :

2024-01-19T23:57:04Z
2024-09-18T09:29:26Z