Thromb Haemost 2010; 103(02): 408-414
DOI: 10.1160/TH09-06-0391
Platelets and Blood Cells
Schattauer GmbH

Loss of high-molecular-weight von Willebrand factor multimers mainly affects platelet aggregation in patients with aortic stenosis

Simon Panzer
1   Clinical Department for Blood Group Serology and Transfusion Medicine, Division of Blood Group Serology, Medical University of Vienna, Vienna, Austria
,
Roza Badr Eslam
2   Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria
,
Alexandra Schneller
1   Clinical Department for Blood Group Serology and Transfusion Medicine, Division of Blood Group Serology, Medical University of Vienna, Vienna, Austria
2   Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria
,
Alexandra Kaider
3   Core Unit for Medical Statistics and Informatics, Section of Clinical Biometrics, Medical University of Vienna, Vienna, Austria
,
Daniela Koren
1   Clinical Department for Blood Group Serology and Transfusion Medicine, Division of Blood Group Serology, Medical University of Vienna, Vienna, Austria
,
Beate Eichelberger
1   Clinical Department for Blood Group Serology and Transfusion Medicine, Division of Blood Group Serology, Medical University of Vienna, Vienna, Austria
,
Raphael Rosenhek
2   Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria
,
Ulrich Budde
4   AescuLabor Hamburg, Hamburg, Germany
,
Irene M. Lang
2   Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria
› Institutsangaben
Financial support: This study was part of the doctorial thesis of AS at the Medical University Vienna.
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Publikationsverlauf

Received: 22. Juni 2009

Accepted after major revision: 06. November 2009

Publikationsdatum:
22. November 2017 (online)

Summary

Severe aortic stenosis is associated with a haemostatic abnormality that resembles acquired von Willebrand syndrome type 2. It is assumed that high shear conditions render large von Willebrand factor (VWF) multimers accessible to cleavage by ADAMTS-13. However, whether loss of these large multimers affects platelet function by impairing adhesion, aggregate formation, or both has not been evaluated in clinical studies. We prospectively enrolled 47 patients with severe aortic stenosis, and studied them prior to aortic valve surgery and at a median of six months after valve replacement. We investigated levels of large VWF multimers, platelet function under high shear conditions, and residual response to suboptimal concentrations of ADP to express P-selectin. As expected, there was a significant reduction of VWF large multimers before surgery that resolved thereafter in most patients (p<0.0001). The closure time of the ADP cartridge of the PFA-100 was also corrected in most patients after the operation (p<0.0001). We used the cone and plate(let) analyser Impact-R to differentiate between adhesion and aggregation. Both adhesion (p=0.03) and ADP-inducible platelet aggregation (p=0.002) improved considerably after valve replacement. Consequently, ADP-inducible expression of P-selectin was higher after valve replacement (p=0.001). We conclude that reduced levels of large VWF multimers associated with aortic stenosis lead to impairment of both adhesion and, especially, ADP-inducible platelet aggregation.

 
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