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Thromb Haemost 1997; 77(02): 387-393
DOI: 10.1055/s-0038-1655973
Original Article
Schattauer GmbH Stuttgart

Acute von Willebrand Factor Secretion from the Endothelium In Vivo: Assessment through Plasma Propeptide (vWf:AgII) Levels

Ulrich M Vischer
1   Division de Biochimie Clinique, HCUG, Geneva, Switzerland
,
Jørgen Ingerslev
2   Hemophilia Center and Coagulation Laboratory, University Hospital Aarhus/Skejby, Aarhus, Denmark
,
Claes B Wollheim
1   Division de Biochimie Clinique, HCUG, Geneva, Switzerland
,
Jean-Claude Mestries
3   CRSSA, La Tronche, France
,
Dimitrios A Tsakiris
4   University Hospital Basel, Basel, Switzerland
,
Walter E Haefeli
4   University Hospital Basel, Basel, Switzerland
,
Egbert K O Kruithof
5   Division d’Angiologie et d’Hémostase, Department of Internal Medicine, HCUG, Geneva, Switzerland
› Author Affiliations
Further Information

Publication History

Received 01 August 1996

Accepted after revision 24 October 1996

Publication Date:
10 July 2018 (online)

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Summary

Elevated plasma concentrations of von Willebrand factor (vWf) are increasingly recognized as a cardiovascular risk factor, and are used as a marker of endothelial activation. However, the factors which determine the rate of vWf release from the endothelium in vivo have not been defined clearly. In addition, vWf plasma levels may also be influenced by adhesion of vWf to the vascular wall or to platelets, and by its rate of degradation. The propeptide of vWf (also called vWf:AgII) is stored and released in equimolar amounts with vWf. In the present study we attempted to determine whether this propeptide could be a more reliable marker of endothelial secretion than vWf itself. To accomplish this we developed an ELISA based on monoclonal antibodies. The propeptide levels in normal plasma were found to be 0.7 µg/ml, more than 10 times lower than vWf itself. Administration of desmopressin (DDAVP) induced a rapid relative increase in propeptide (from 106 to 879%) and in vWf (from 112 to 272%). However, the increases in vWf and propeptide were equivalent when expressed in molar units. A time course study indicated a half-life of the propeptide of 3 h or less. In a baboon model of disseminated intravascular coagulation (DIC) induced by FXa, vWf increased by less than 100%, whereas the propeptide concentrations increased by up to 450%. In view of the massive thrombin generation (as assessed by fibrinogen depletion), the increases in vWf are small, compared to the strong secretory response to thrombin and fibrin previously observed in vitro. Our results suggest that due to its rapid turnover, the propeptide could provide a sensitive plasma marker of acute endothelial secretion.

 

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