Elevated levels of von Willebrand Factor in cirrhosis support platelet adhesion despite reduced functional capacity

Authors

  • Ton Lisman,

    Corresponding author
    1. Thrombosis and Haemostasis Laboratory, Department of Haematology, University Medical Centre, Utrecht
    2. Institute of Biomembranes, Utrecht University, Utrecht
    • Thrombosis and Haemostasis Laboratory, Department of Haematology G.03.550, University Medical Centre, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
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    • fax: (31) 30-2505418

    • Ton Lisman and Tamara N. Bongers contributed equally to this study.

  • Tamara N. Bongers,

    1. Department of Haematology of the Erasmus University Medical Center, Rotterdam, The Netherlands
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    • Ton Lisman and Tamara N. Bongers contributed equally to this study.

  • Jelle Adelmeijer,

    1. Thrombosis and Haemostasis Laboratory, Department of Haematology, University Medical Centre, Utrecht
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  • Harry L.A. Janssen,

    1. Department of Gastroenterology & Hepatology of the Erasmus University Medical Center, Rotterdam, The Netherlands
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  • Moniek P.M. de Maat,

    1. Department of Haematology of the Erasmus University Medical Center, Rotterdam, The Netherlands
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  • Philip G. de Groot,

    1. Thrombosis and Haemostasis Laboratory, Department of Haematology, University Medical Centre, Utrecht
    2. Institute of Biomembranes, Utrecht University, Utrecht
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  • Frank W.G. Leebeek

    1. Department of Haematology of the Erasmus University Medical Center, Rotterdam, The Netherlands
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  • Potential conflict of interest: Nothing to report.

Abstract

Cirrhosis of the liver is frequently accompanied by complex alterations in the hemostatic system, resulting in a bleeding tendency. Although many hemostatic changes in liver disease promote bleeding, compensatory mechanisms also are found, including high levels of the platelet adhesive protein von Willebrand Factor (VWF). However, conflicting reports on the functional properties of VWF in cirrhosis have appeared in literature. We have measured a panel of VWF parameters in plasma from patients with cirrhosis of varying severity and causes. Furthermore, we assessed the contribution of VWF to platelet adhesion, by measuring the ability of plasma from patients with cirrhosis to support adhesion of normal or patient platelets under flow conditions. VWF antigen levels were strongly increased in patients with cirrhosis. In contrast, the relative collagen binding activity, as well as the relative ristocetin cofactor activity, was significantly lower in patients as compared with controls, indicating loss of function. Accordingly, patients had a reduced fraction of high-molecular-weight VWF multimers. Both strongly elevated and reduced activity and antigen levels of the VWF cleaving protease ADAMTS13 were found in individual patients. Adhesion of either normal or patient platelets to a collagen surface was substantially increased when these platelets were resuspended in plasma of patients with cirrhosis, as compared with control plasma. In conclusion, highly elevated levels of VWF in patients with cirrhosis contribute to the induction of primary hemostasis despite reduced functional properties of the molecule. This phenomenon might compensate for defects in platelet number and function in patients with cirrhosis. (HEPATOLOGY 2006;44:53–61.)

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