Document Detail


ADAMTS13 activity is decreased in a septic porcine model. Significance for glomerular thrombus deposition.
MedLine Citation:
PMID:  21057705     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
During sepsis, the balance between abundantly secreted von Willebrand factor (VWF) and the activity of its size regulating protease ADAMTS13 is assumed to be involved in coagulation abnormalities. We aimed to establish a porcine model with haemorrhagic shock with consecutive sepsis and hypothesised that a decreased ADAMTS13-activity as well as an altered VWF multimer pattern is associated with renal failure. Animals (n=21) were subjected to haemorrhagic shock. After volume replacement, intraperitoneal Escherichia coli sepsis was induced. Blood samples were drawn at baseline, after haemorrhage and sepsis induction. Directly postmortem we examined renal tissue by JONES-silver, CD61, VWF and fibrin staining for characterisation of thrombi. Renal failure was analysed by scoring PAS-stained sections for acute tubular damage. Glomerular microthrombi were observed in six of 21 septic animals. Porcine ADAMTS13 activity declined significantly during sepsis, accompanied by a drop-off in platelet count. At 12 hours after sepsis induction, ADAMTS13 activity was significantly diminished compared to sham controls, and an elevated acute tubular damage score was associated with an increased proportion of high-molecular-weight VWF multimers. Compared to baseline the proportion of high-molecular-weight VWF multimers increased significantly in septic animals. Similar to human sepsis, diminished ADAMTS13 activity was observed in a septic porcine model associated with a shift to rather thrombogenic VWF multimers and deposition of microthrombi. Therefore, this porcine model seems to be appropriate for performing functional and therapeutic studies in sepsis-associated ADAMTS13 deficiency.
Authors:
Clemens L Bockmeyer; Phillipp A Reuken; Tim P Simon; Ulrich Budde; Wolfgang Lösche; Michael Bauer; Ingvild Birschmann; Jan U Becker; Gernot Marx; Ralf A Claus
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Publication Detail:
Type:  Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-11-05
Journal Detail:
Title:  Thrombosis and haemostasis     Volume:  105     ISSN:  0340-6245     ISO Abbreviation:  Thromb. Haemost.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-04     Completed Date:  2011-05-18     Revised Date:  2011-05-23    
Medline Journal Info:
Nlm Unique ID:  7608063     Medline TA:  Thromb Haemost     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  145-53     Citation Subset:  IM    
Affiliation:
Department of Anaesthesiology and Intensive Care, Jena University Hospital, Jena, Germany.
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MeSH Terms
Descriptor/Qualifier:
ADAM Proteins / metabolism*
Animals
Disease Models, Animal*
Escherichia coli
Protein Multimerization
Renal Insufficiency / etiology
Sepsis / complications*
Shock, Hemorrhagic / complications*
Swine
Thrombosis / etiology*
von Willebrand Factor / metabolism
Chemical
Reg. No./Substance:
0/von Willebrand Factor; EC 3.4.24.-/ADAM Proteins; EC 3.4.24.-/ADAMTS13 protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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