ADAMTS13 activity is decreased in a septic porcine model. Significance for glomerular thrombus deposition.
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.
Department of Anaesthesiology and Intensive Care, Jena University Hospital, Jena, Germany.
Clemens L
CL
Bockmeyer
Phillipp A
PA
Reuken
Tim P
TP
Simon
Ulrich
U
Budde
Wolfgang
W
Lösche
Michael
M
Bauer
Ingvild
I
Birschmann
Jan U
JU
Becker
Gernot
G
Marx
Ralf A
RA
Claus
D051722:ADAM Proteins / Q000378:metabolism*; D000071120:ADAMTS13 Protein; D000818:Animals; D004195:Disease Models, Animal; D004926:Escherichia coli; D055503:Protein Multimerization; D051437:Renal Insufficiency / Q000209:etiology; D018805:Sepsis / Q000150:complications*; D012771:Shock, Hemorrhagic / Q000150:complications*; D013552:Swine; D013927:Thrombosis / Q000209:etiology*; D014841:von Willebrand Factor / Q000378:metabolism
D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human