Variations in the ratio between von Willebrand factor and its cleaving protease during systemic inflammation and association with severity and prognosis of organ failure

Ralf A. Claus; Clemens L. Bockmeyer; Ulrich Budde; Karim Kentouche; Maik Sossdorf; Thomas Hilberg; Reinhart Schneppenheim; Konrad Reinhart; Michael Bauer; Frank M. Brunkhorst; Wolfgang Lösche

doi:10.1160/TH08-03-0161

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2009; 101(02): 239-247
DOI: 10.1160/TH08-03-0161

Theme Issue Article

Schattauer GmbH

Variations in the ratio between von Willebrand factor and its cleaving protease during systemic inflammation and association with severity and prognosis of organ failure

Ralf A. Claus

¹Department of Anaesthesiology and Intensive Care Medicine, University Hospital, Friedrich-Schiller-University, Jena, Germany

,

Clemens L. Bockmeyer^*

¹Department of Anaesthesiology and Intensive Care Medicine, University Hospital, Friedrich-Schiller-University, Jena, Germany

,

Ulrich Budde

²AescuLabor Hamburg, Institute for Laboratory Medicine, Hamburg, Germany

,

Karim Kentouche

³Department of Pediatrics, University Hospital, Friedrich-Schiller-University, Jena, Germany

,

Maik Sossdorf

¹Department of Anaesthesiology and Intensive Care Medicine, University Hospital, Friedrich-Schiller-University, Jena, Germany

⁴Department of Sports Medicine, Friedrich-Schiller-University Jena, Germany

,

Thomas Hilberg

⁴Department of Sports Medicine, Friedrich-Schiller-University Jena, Germany

,

Reinhart Schneppenheim

⁵Children‘s University Hospital Hamburg-Eppendorf, Department of Pediatric Hematology and Oncology, Germany

,

Konrad Reinhart

¹Department of Anaesthesiology and Intensive Care Medicine, University Hospital, Friedrich-Schiller-University, Jena, Germany

,

Michael Bauer

¹Department of Anaesthesiology and Intensive Care Medicine, University Hospital, Friedrich-Schiller-University, Jena, Germany

,

Frank M. Brunkhorst

¹Department of Anaesthesiology and Intensive Care Medicine, University Hospital, Friedrich-Schiller-University, Jena, Germany

,

Wolfgang Lösche

¹Department of Anaesthesiology and Intensive Care Medicine, University Hospital, Friedrich-Schiller-University, Jena, Germany

› Author Affiliations

Abstract

Summary

Von Willebrand factor (VWF) and related parameters as well as the protease activity regulating its biological activity were measured in plasma of healthy controls and patients with different cause and severity of systemic inflammation to examine the efficacy of the measures to detect highly prothrombotic states including thrombotic microangiopathy (TMA), one of the sequelae of sepsis. Plasma levels of VWF increased with increasing severity of systemic inflammation, probably due to activation of the endothelium. In parallel, the proteolytic activity of VWF inactivating protease, ADAMTS13, stepwise declined with the severity of inflammation, emphasizing the role of VWF-triggered platelet aggregation on the endothelium subsequently followed by development of TMA. As a consequence, the ratio of VWF antigen level and ADAMTS13 activity was significantly higher in patients with inflammation and sepsis, suggesting that this ratio might be more useful for the diagnosis of highly prothrombotic states including TMA than VWF multimer analysis alone. These findings suggest that ADAMTS13, VWF and related parameters, even in a combined approach, might be useful for the diagnosis and the therapeutic monitoring of patients with sepsis associated thrombotic microangiopathy.

Keywords

ADAMTS13 - sepsis - systemic inflammation - organ failure - platelets - thrombotic microangiopathy - TMA-index

Full Text

References

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