Download PDF
Semin Thromb Hemost 2011; 37(5): 503-510
DOI: 10.1055/s-0031-1281036
© Thieme Medical Publishers

Diagnosis and Management of von Willebrand Disease in Spain

Javier Batlle1 , 2 , Almudena Perez-Rodriguez1 , Joana Costa Pinto1 , Esther Loures Fraga N.R.1 , Angela Rodriguez-Trillo Tch1 , Maria Fernanda Lopez-Fernandez1 on behalf of participant investigators and centers*
  • 1Haematology and Haemotherapy Service and INIBIC, Complexo Hospitalario Universitario de A Coruna, A Coruna, Spain
  • 2Department of Medicine, University of Santiago de Compostela, A Coruña, Spain
Further Information

Publication History

Publication Date:
18 November 2011 (online)

    Permissions and Reprints

ABSTRACT

The correct diagnosis and classification of von Willebrand disease (VWD) is important for therapy and genetic counseling but is made difficult due to the variability of its clinical expression and limitations of laboratory methods. A national registry of VWD patients has been initiated in Spain. The results of a concise survey on the diagnosis of VWD show the frequency of VWD is fivefold greater in Spain than that expected from epidemiological studies in other European countries; this may result from overdiagnosis and/or a higher prevalence of VWD. These results clearly reinforce the need for the Spanish VWD registry. A consensus guideline for optimal treatment of VWD is being elaborated in Spain. Desmopressin (DDAVP) is the choice of treatment in responsive VWD patients. von Willebrand factor concentrates (VWF/factor VIII) are used in individuals nonresponsive to DDAVP, when DDAVP is contraindicated, or in VWD types 2B and 3.

KEYWORDS

von Willebrand disease - VWD - von Willebrand factor - VWF - survey - diagnosis - therapy

REFERENCES

  • 1 Batlle J, Villar A, Liras A et al.. Consensus opinion for the selection and use of therapeutic products for the treatment of haemophilia in Spain.  Blood Coagul Fibrinolysis. 2008;  19 (5) 333-340
    Google Scholar
  • 2 Aznar J A, Lucia F, Abad-Franch L et al.. Haemophilia in Spain.  Haemophilia. 2009;  15 (3) 665-675
    Google Scholar
  • 3 Aznar J A, Abad-Franch L, Cortina V, Marco P. Inherited Bleeding Disorders Group from the Spanish Society of Thrombosis and Haemostasis . The national registry of haemophilia A and B in Spain: results from a census of patients.  Haemophilia. 2009;  15 1327-1353
    Google Scholar
  • 4 Rodeghiero F, Castaman G. von Willebrand disease: epidemiology. In: Lee C A, Berntorp E E, Hoots W K, eds. Textbook of Hemophilia. Oxford, United Kingdom: Blackwell; 2005: 265-272
    Google Scholar
  • 5 Federici A B, Canciani M T. Clinical and laboratory versus molecular markers for a correct classification of von Willebrand disease.  Haematologica. 2009;  94 610-615
    Google Scholar
  • 6 Nichols W L, Hultin M B, James A H et al.. von Willebrand disease (VWD): evidence-based diagnosis and management guidelines, the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel report (USA).  Haemophilia. 2008;  14 (2) 171-232
    Google Scholar
  • 7 Favaloro E J. Toward a new paradigm for the identification and functional characterization of von Willebrand disease.  Semin Thromb Hemost. 2009;  35 (1) 60-75
    Google Scholar
  • 8 Sadler J E, Budde U, Eikenboom J C et al.. Working Party on von Willebrand Disease Classification. Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor.  J Thromb Haemost. 2006;  4 (10) 2103-2114
    Google Scholar
  • 9 Batlle J, Perez-Rodriguez A, Lopez-Fernandez M F. Classification of VWD. In: Federici A, Lee C, Berntorp E, et al, eds. von Willebrand Disease: Basic and Clinical Aspects. Oxford, United Kingdom: Blackwell; 2010: 74-85
    Google Scholar
  • 10 Batlle J, Perez-Rodriguez A, Loures E, Rodriguez-Trillo A, Lopez-Fernandez M F. Metodos diagnosticos en la enfermedad de von Willebrand. LI Reunión Nacional de la AEHH; XXV Congreso Nacional de la SETH. Barcelona.  Haematologica (Edición española). 2009;  93 (Suplemento 1) 18-22
    Google Scholar
  • 11 Penas N, Perez-Rodriguez A, Torea J H et al.. von Willebrand disease R1374C: type 2A or 2M? A challenge to the revised classification. High frequency in the northwest of Spain (Galicia).  Am J Hematol. 2005;  80 (3) 188-196
    Google Scholar
  • 12 Perez-Rodriguez A, Garcia-Rivero A, Loures E, Lopez-Fernandez M F, Rodriguez-Trillo A, Batlle J. Autosomal dominant C1149R von Willebrand disease: phenotypic findings and their implications.  Haematologica. 2009;  94 (5) 679-686
    Google Scholar
  • 13 Batlle J, Perez-Rodriguez A, Franqueira M D, Lopez-Fernandez M F. Type 2M von Willebrand disease: a variant of type 2A?.  J Thromb Haemost. 2008;  6 (2) 388-390
    Google Scholar
  • 14 Rodeghiero F, Castaman G, Dini E. Epidemiological investigation of the prevalence of von Willebrand's disease.  Blood. 1987;  69 (2) 454-459
    Google Scholar
  • 15 Sadler J E, Mannucci P M, Berntorp E et al.. Impact, diagnosis and treatment of von Willebrand disease.  Thromb Haemost. 2000;  84 (2) 160-174
    Google Scholar
  • 16 Federici A B, Castaman G, Mannucci P M. Guidelines for the diagnosis and treatment of von Willebrand disease in Italy. Italian Association of Haemophilia Centers (AICE).  Haemophilia. 2002;  8 607-611
    Google Scholar
  • 17 Batlle J, Lopez-Fernandez M F, Fraga E L, Trillo A R, Perez-Rodriguez M A. von Willebrand factor/factor VIII concentrates in the treatment of von Willebrand disease.  Blood Coagul Fibrinolysis. 2009;  20 (2) 89-100
    Google Scholar
  • 18 Budde U, Schneppenheim R, Eikenboom J et al.. Detailed von Willebrand factor multimer analysis in patients with von Willebrand disease in the European study, molecular and clinical markers for the diagnosis and management of type 1 von Willebrand disease (MCMDM-1VWD).  J Thromb Haemost. 2008;  6 (5) 762-771
    Google Scholar
  • 19 Tosetto A, Rodeghiero F, Castaman G et al.. Impact of plasma von Willebrand factor levels in the diagnosis of type 1 von Willebrand disease: results from a multicenter European study (MCMDM-1VWD).  J Thromb Haemost. 2007;  5 (4) 715-721
    Google Scholar
  • 20 Goodeve A, Eikenboom J, Castaman G et al.. Phenotype and genotype of a cohort of families historically diagnosed with type 1 von Willebrand disease in the European study, Molecular and Clinical Markers for the Diagnosis and Management of Type 1 von Willebrand Disease (MCMDM-1VWD).  Blood. 2007;  109 (1) 112-121
    Google Scholar
  • 21 Tosetto A, Rodeghiero F, Castaman G et al.. A quantitative analysis of bleeding symptoms in type 1 von Willebrand disease: results from a multicenter European study (MCMDM-1 VWD).  J Thromb Haemost. 2006;  4 (4) 766-773
    Google Scholar
  • 22 Rodeghiero F, Castaman G, Tosetto A et al.. The discriminant power of bleeding history for the diagnosis of type 1 von Willebrand disease: an international, multicenter study.  J Thromb Haemost. 2005;  3 (12) 2619-2626
    Google Scholar
  • 23 Castaman G, Lethagen S, Federici A B et al.. Response to desmopressin is influenced by the genotype and phenotype in type 1 von Willebrand disease (VWD): results from the European Study MCMDM-1VWD.  Blood. 2008;  111 (7) 3531-3539
    Google Scholar
  • 24 Eikenboom J, Van Marion V, Putter H et al.. Linkage analysis in families diagnosed with type 1 von Willebrand disease in the European study, molecular and clinical markers for the diagnosis and management of type 1 VWD.  J Thromb Haemost. 2006;  4 (4) 774-782
    Google Scholar
  • 25 Haberichter S L, Castaman G, Budde U et al.. Identification of type 1 von Willebrand disease patients with reduced von Willebrand factor 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).  Blood. 2008;  111 (10) 4979-4985
    Google Scholar
  • 26 Castaman G, Tosetto A, Goodeve A et al.. The impact of bleeding history, von Willebrand factor and PFA-100(®) on the diagnosis of type 1 von Willebrand disease: results from the European study MCMDM-1VWD.  Br J Haematol. 2010;  151 (3) 245-251
    Google Scholar
  • 27 Castaman G, Tosetto A, Cappelletti A et al.. Validation of a rapid test (VWF-LIA) for the quantitative determination of von Willebrand factor antigen in type 1 von Willebrand disease diagnosis within the European multicenter study MCMDM-1VWD.  Thromb Res. 2010;  126 (3) 227-231
    Google Scholar
  • 28 Eikenboom J, Hilbert L, Ribba A S et al.. Expression of 14 von Willebrand factor mutations identified in patients with type 1 von Willebrand disease from the MCMDM-1VWD study.  J Thromb Haemost. 2009;  7 (8) 1304-1312
    Google Scholar

Javier BatlleMD 

Department of Medicine, University of Santiago de Compostela

Spain. A Coruna (Hospital Materno Infantil building). Carretera del Pasaje s/n. 15006 - A Coruña. España

Email: Francisco.Javier.Batlle.Fonrodona@sergas.es

      >