Published online 13 March 2009
Haematologica, Vol 94, Issue 5, 679-686 doi:10.3324/haematol.2008.003301
Copyright © 2009 by Ferrata Storti Foundation
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Disorders of Hemostasis

Autosomal dominant C1149R von Willebrand disease: phenotypic findings and their implications

Almudena Pérez-Rodríguez1, Aranzazu García-Rivero2, Esther Lourés1, Maria Fernanda López-Fernández1, Angela Rodríguez-Trillo1, Javier Batlle1

1 Servicio de Hematología y Hemoterapia, Complexo Hospitalario Universitario Juan Canalejo, A Coruña, Department of Medicine, School of Medicine, University of Santiago de Compostela
2 Centro Oncológico de Galicia, La Coruña, Spain

Correspondence: Francisco Javier Batlle, Fonrodona, M.D., Servicio, de Hematología y Hemoterapia, Complexo Hospitalario, Universitario Juan Canalejo, (Edificio Hospital Materno Infantil), Carretera del Pasaje, s/n. 15006, La Coruña, Spain., E-mail:Francisco.Javier.Batlle.Fonrodona{at}sergas.es

Background: Mutation C1149R in the von Willebrand factor (VWF) gene has been thought to cause autosomal dominant severe type 1 von Willebrand disease (VWD).

Design and Methods: Eight patients from three unrelated families with this mutation were included in the present study who had distinct VWF abnormalities, not described in earlier studies.

Results: The patients showed notably low levels of VWF antigen (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo), VWF collagen binding (VWF:CB), and a reduced ristocetin-induced platelet aggregation (RIPA). VWF:RCo/VWF:Ag and VWF:CB/VWF:Ag ratios were lower than 0.7. At basal conditions, all the VWF multimers were decreased in plasma, with a clearly lower relative proportion of the high molecular weight VWF multimers (HMWM). In high-resolution agarose gels, a large decrease in the relative proportions of the satellite bands was seen. The patients had a brief good response to desmopressin (DDAVP) administration, but the released VWF half-life was shorter than normal, indicating an accelerated clearance of their VWF. Platelet VWF was abnormal.

Conclusions: We conclude from the results obtained in these patients for plasma phenotypic data that this mutation should be classified as a VWD type 2A (IIE). DDAVP therapy may be somewhat helpful for this mutation, at least for mild to moderate bleeding. These data provide evidence that for VWD classification factors other than basal VWF, such as DDAVP response and platelet VWF, should be considered.

Key words: C1149R von Willebrand disease, platelet von Willebrand factor, VWD type 2A (IIE), desmopressin, von Willebrand factor.


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Clinical and laboratory versus molecular markers for a correct classification of von Willebrand disease
Augusto B Federici, Maria T. Canciani
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A. B Federici and M. T. Canciani
Clinical and laboratory versus molecular markers for a correct classification of von Willebrand disease
Haematologica, May 1, 2009; 94(5): 610 - 615.
[Full Text] [PDF]