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Blood, 15 May 2008, Vol. 111, No. 10, pp. 4979-4985.
Prepublished online as a Blood First Edition Paper on March 14, 2008; DOI 10.1182/blood-2007-09-110940.
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Submitted September 6, 2007
Accepted February 19, 2008
Identification of type 1 von Willebrand disease patients with reduced von Willebrand factor (VWF) survival by assay of the VWF propeptide in the European study: molecular and clinical markers for the diagnosis and management of type 1 VWD (MCMDM-1VWD)
Sandra L Haberichter*, Giancarlo Castaman, Ulrich Budde, Ian Peake, Anne Goodeve, Francesco Rodeghiero, Augusto B. Federici, Javier Batlle, Dominique Meyer, Claudine Mazurier, Jenny Goudemand, Jeroen Eikenboom, Reinhard Schneppenheim, Jorgen Ingerslev, Zdena Vorlova, David Habart, Lars Holmberg, Stefan Lethagen, John Pasi, Frank G.H. Hill, and Robert R. Montgomery
Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, United States
San Bortolo Hospital, Vicenza, Italy
Coagulation Laboratory, Hamburg, Germany
University of Sheffield, Sheffield, United Kingdom
IRCCS Foundation Maggiore Hospital, University of Milan, Milan, Italy
Hospital Teresa Herrera, La Coruna, Spain
INSERM, Unite 770, Paris, France
LFB, Lille, Faroe Islands
University of Lille, Lille, France
Leiden University Medical Center, Leiden, Netherlands
Department of Pediatric Hematology and Oncology, Universtiy Medical Center Hamburg-Eppendorf, Hamburg, Germany
University Hospital Skejby, Aarhus, Denmark
Institute of Hematology and Blood Transfusion, Prague, Czech Republic
University of Lund, Malmo, Sweden
Barts and The London, Queen Mary University of London, Leicester, United Kingdom
The Birmingham Children's Hospital NHS Trust, Birmingham, United Kingdom
Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI, United States
* Corresponding author; email: shaberic{at}mcw.edu.
The decreased survival of von Willebrand factor (VWF) in plasma has been implicated as a mechanism in a subset of type 1 von Willebrand disease (VWD) patients. We have previously reported that the ratio of plasma levels of VWF and its propeptide (VWFpp) can be used to identify patients with reduced VWF survival. In this study, we report the assay of VWFpp and VWF:Ag in 19 individuals recruited from 6 European centers within the MCMDM-1VWD study. Eight individuals had a VWF:Ag level less than 30 IU/dL. Seven of these patients had a robust desmopressin response and significantly reduced VWF half-life that was predicted by a markedly increased steady-state plasma VWFpp/VWF:Ag ratio. VWF mutations previously associated with reduced VWF survival were identified in each of the seven individuals. Thus, a substantially increased ratio of steady-state VWFpp/VWF:Ag predicted a reduced VWF half-life in patients with markedly decreased VWF:Ag levels. These data indicate that a reduced VWF survival is found in a subpopulation of patients with type 1 VWD. The systematic assay of both plasma VWF and the VWF propeptide in moderately severe type 1 VWD patients may identify patients with a reduced VWF survival phenotype.
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