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DYNAMIC CHANGES IN THROMBIN GENERATION IN ABDOMINAL SEPSIS IN MICE.

Wang, Yongzhi LU ; Braun, Oscar LU ; Zhang, Su LU ; Luo, Ling Tao LU ; Norström, Eva LU and Thorlacius, Henrik LU (2014) In Shock 42(4). p.343-349
Abstract
ABSTRACT-Systemic inflammatory response syndrome and severe infections are associated with major derangements in the coagulation system. The purpose of this study was to examine the dynamic alterations in thrombin generation in abdominal sepsis. Abdominal sepsis was induced by cecal ligation and puncture (CLP) in C57/Bl6 mice. CLP caused a systemic inflammatory response with neutrophil recruitment and tissue damage in the lung as well as thrombocytopenia and leukocytopenia. Thrombin generation, coagulation factors, lung histology and myeloperoxidase (MPO) activity was determined 1h, 3h, 6h and 24h after induction of CLP. It was found that thrombin generation was increased 1h after CLP and that thrombin generation started to decrease at 3h... (More)
ABSTRACT-Systemic inflammatory response syndrome and severe infections are associated with major derangements in the coagulation system. The purpose of this study was to examine the dynamic alterations in thrombin generation in abdominal sepsis. Abdominal sepsis was induced by cecal ligation and puncture (CLP) in C57/Bl6 mice. CLP caused a systemic inflammatory response with neutrophil recruitment and tissue damage in the lung as well as thrombocytopenia and leukocytopenia. Thrombin generation, coagulation factors, lung histology and myeloperoxidase (MPO) activity was determined 1h, 3h, 6h and 24h after induction of CLP. It was found that thrombin generation was increased 1h after CLP and that thrombin generation started to decrease at 3h and was markedly reduced 6h and 24h after CLP induction. Platelet poor plasma from healthy mice could completely reverse the inhibitory effect of CLP on thrombin generation, suggesting that sepsis caused a decrease in the levels of plasma factors regulating thrombin generation in septic animals. Indeed, it was found that CLP markedly decreased plasma levels of prothrombin, factor V and factor X at 6h and 24h. Moreover, we observed that CLP increased plasma levels of activated protein C at 6h, which returned to baseline levels 24h after CLP induction. Finally, pretreatment with imipenem/cilastatin attenuated the CLP-evoked decrease in thrombin generation and consumption of prothrombin 24h after CLP induction. Our novel findings suggest that thrombin generation is initially increased and later decreased in abdominal sepsis. Sepsis-induced reduction in thrombin generation is correlated to changes in the plasma levels of coagulation factors and activated protein C. These findings help explain the dynamic changes in global hemostasis in abdominal sepsis. (Less)
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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Shock
volume
42
issue
4
pages
343 - 349
publisher
Lippincott Williams & Wilkins
external identifiers
  • pmid:24978891
  • wos:000342465100009
  • scopus:84914684643
  • pmid:24978891
ISSN
1540-0514
DOI
10.1097/SHK.0000000000000215
language
English
LU publication?
yes
id
61cbc03a-d46f-4e17-8e2b-b9d8e445a2e9 (old id 4583968)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24978891?dopt=Abstract
date added to LUP
2016-04-01 11:14:07
date last changed
2022-02-03 00:43:51
@article{61cbc03a-d46f-4e17-8e2b-b9d8e445a2e9,
  abstract     = {{ABSTRACT-Systemic inflammatory response syndrome and severe infections are associated with major derangements in the coagulation system. The purpose of this study was to examine the dynamic alterations in thrombin generation in abdominal sepsis. Abdominal sepsis was induced by cecal ligation and puncture (CLP) in C57/Bl6 mice. CLP caused a systemic inflammatory response with neutrophil recruitment and tissue damage in the lung as well as thrombocytopenia and leukocytopenia. Thrombin generation, coagulation factors, lung histology and myeloperoxidase (MPO) activity was determined 1h, 3h, 6h and 24h after induction of CLP. It was found that thrombin generation was increased 1h after CLP and that thrombin generation started to decrease at 3h and was markedly reduced 6h and 24h after CLP induction. Platelet poor plasma from healthy mice could completely reverse the inhibitory effect of CLP on thrombin generation, suggesting that sepsis caused a decrease in the levels of plasma factors regulating thrombin generation in septic animals. Indeed, it was found that CLP markedly decreased plasma levels of prothrombin, factor V and factor X at 6h and 24h. Moreover, we observed that CLP increased plasma levels of activated protein C at 6h, which returned to baseline levels 24h after CLP induction. Finally, pretreatment with imipenem/cilastatin attenuated the CLP-evoked decrease in thrombin generation and consumption of prothrombin 24h after CLP induction. Our novel findings suggest that thrombin generation is initially increased and later decreased in abdominal sepsis. Sepsis-induced reduction in thrombin generation is correlated to changes in the plasma levels of coagulation factors and activated protein C. These findings help explain the dynamic changes in global hemostasis in abdominal sepsis.}},
  author       = {{Wang, Yongzhi and Braun, Oscar and Zhang, Su and Luo, Ling Tao and Norström, Eva and Thorlacius, Henrik}},
  issn         = {{1540-0514}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{343--349}},
  publisher    = {{Lippincott Williams & Wilkins}},
  series       = {{Shock}},
  title        = {{DYNAMIC CHANGES IN THROMBIN GENERATION IN ABDOMINAL SEPSIS IN MICE.}},
  url          = {{http://dx.doi.org/10.1097/SHK.0000000000000215}},
  doi          = {{10.1097/SHK.0000000000000215}},
  volume       = {{42}},
  year         = {{2014}},
}