ADAMTS13 activity is decreased in a septic porcine model

Clemens L. Bockmeyer; Philipp A. Reuken; Tim P. Simon; Ulrich Budde; Wolfgang Lösche; Michael Bauer; Ingvild Birschmann; Jan U. Becker; Gernot Marx; Ralf A. Claus

doi:10.1160/TH10-03-0153

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2011; 105(01): 131-137
DOI: 10.1160/TH10-03-0153

Animal Models

Schattauer GmbH

ADAMTS13 activity is decreased in a septic porcine model

Significance for glomerular thrombus deposition

Clemens L. Bockmeyer

¹Department of Anaesthesiology and Intensive Care, Jena University Hospital, Jena, Germany

²Institute for Pathology, Hannover Medical School, Hannover, Germany

,

Philipp A. Reuken

¹Department of Anaesthesiology and Intensive Care, Jena University Hospital, Jena, Germany

,

Tim P. Simon

³Department of Intensive Care Medicine, University Hospital Aachen, Aachen, Germany

,

Ulrich Budde

⁴Aesculabor, Institute for Laboratory Medicine, Hamburg, Germany

,

Wolfgang Lösche

¹Department of Anaesthesiology and Intensive Care, Jena University Hospital, Jena, Germany

,

Michael Bauer

¹Department of Anaesthesiology and Intensive Care, Jena University Hospital, Jena, Germany

,

Ingvild Birschmann

⁵Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany

,

Jan U. Becker

²Institute for Pathology, Hannover Medical School, Hannover, Germany

,

Gernot Marx^*

³Department of Intensive Care Medicine, University Hospital Aachen, Aachen, Germany

,

Ralf A. Claus^*

¹Department of Anaesthesiology and Intensive Care, Jena University Hospital, Jena, Germany

› Author Affiliations

Abstract

Summary

During sepsis, the balance between abundantly secreted von Wille-brand 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.

Keywords

Platelets - von Willebrand factor - renal failure - sepsis - thrombotic micro-angiopathy - multiple organ failure - histology

Full Text

References

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