Changes in ADAMTS13 (von-Willebrand-factor-cleaving protease) activity after induced release of von Willebrand factor during acute systemic inflammation

Rosemarie A. Reiter; Katalin Varadi; Peter L. Turecek; Bernd Jilma; Paul Knöbl

doi:10.1160/TH04-08-0467

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2005; 93(03): 554-558
DOI: 10.1160/TH04-08-0467

Wound Healing and Inflammation/Infection

Schattauer GmbH

Changes in ADAMTS13 (von-Willebrand-factor-cleaving protease) activity after induced release of von Willebrand factor during acute systemic inflammation

Rosemarie A. Reiter

¹Department of Clinical Pharmacology, Medical University of Vienna, Ausria

,

Katalin Varadi

²Baxter Bioscience, Vienna, Austria

,

Peter L. Turecek

²Baxter Bioscience, Vienna, Austria

,

Bernd Jilma

¹Department of Clinical Pharmacology, Medical University of Vienna, Ausria

,

Paul Knöbl

³Department of Medicine 1, Medical University of Vienna, Ausria

› Author Affiliations

Abstract

Summary

Von Willebrand factor (VWF) is synthesized in endothelial cells, stored in the form of high molecular weight multimers and released after stimulation. After release, the multimers are cleaved by ADAMTS13 (von-Willebrand-factor-cleaving protease). We studied healthy volunteers in a double-blind, placebo controlled inflammation model. Ten male volunteers received 2 ng/kg endotoxin intravenously, and 5 volunteers placebo. Endotoxin infusion induced systemic inflammation and coagulation activation. After 4 hours the observed increase in neutrophils reached a maximum (273±34 % of baseline; mean ± SEM) and the platelet count dropped (81±2 %). These parameters returned to baseline values after 24 hours. VWF antigen increased to 259±16 % of baseline after 4 hours, remained elevated (192±15 %) after 24 hours and returned to baseline after 7 days. Unusually large VWF multimers occurred in the plasma 4 hours after endotoxin infusion. ADAMTS13 activity (measured with a collagen-binding assay) decreased to 64±5 % of baseline (P< 0.001) after 4 hours, was still reduced after 24 hours (86±6 %; P=0.008) and returned to normal after 7 days. VWF multimer analysis showed pronounced satellite bands in the 4-hour samples, indicating cleavage of VWF by ADAMTS13. No apparent changes of the analyzed parameters were observed in the placebo group. The reciprocal course of ADAMTS13 and VWF after short-term VWF release induced by systemic inflammation is similar to that observed after induction of VWF release by desmopressin.

Keywords

von Willebrand factor - ADAMTS13 - systemic inflammation - endotoxin

Full Text

References

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