@article{AOB4264,
author = {Javier Batlle and Almudena Pérez-Rodríguez and Irene Corrales and Nina Borràs and Ángela Rodríguez-Trillo and Esther Lourés and Ana Rosa Cid and Santiago Bonanad and Noelia Cabrera and Andrés Moret and Rafael Parra and María Eva Mingot-Castellano and Nira Navarro and Carmen Altisent and Rocío Pérez-Montes and Shally Marcellini and Ana Moretó and Sonia Herrero and Inmaculada Soto and Nuria Fernández-Mosteirín and Víctor Jiménez-Yuste and Nieves Alonso and Aurora de Andrés Jacob and Emilia Fontanes and Rosa Campos and María José Paloma and Nuria Bermejo and Rubén Berrueco and José Mateo and Karmele Arribalzaga and Pascual Marco and Ángeles Palomo and Nerea Castro Quismondo and Belén Iñigo and María del Mar Nieto and Rosa Vidal and María Paz Martínez and Reyes Aguinaco and María Tenorio and María Ferreiro and Javier García-Frade and Ana María Rodríguez-Huerta and Jorge Cuesta and Ramón Rodríguez-González and Faustino García-Candel and Manuela Dobón and Carlos Aguilar and Fernando Batlle López and Francisco Vidal and María Fernanda López-Fernández},
title = {Diagnosis and management of von willebrand disease in Spain},
journal = {Annals of Blood},
volume = {3},
number = {1},
year = {2018},
keywords = {},
abstract = {The correct diagnosis and classification of von Willebrand disease (VWD) is difficult because of the variability of its clinical expression and limitations of laboratory methods. However, correctly diagnosing VWD is important for therapy and genetic counselling. A survey related to the referred VWD patients in Spain revealed local diagnostic problems in at least one third of the cases of VWD. Consequently, a Spanish multicenter study was carried out in which a cohort of 556 patients from 330 families was analyzed centrally. VWD was confirmed in 480 patients. Next generation sequencing (NGS) of the whole coding von Willebrand factor gene (VWF) was carried out in all recruited patients, compared with the phenotype, and a final diagnosis was established. A total of 238 different VWF mutations were found: 154 were not included in the Leiden Open Variation Database (LOVD). Of the patients, 467 were found to have a VWF mutation/s. A good phenotype/genotype association was estimated in 94.6% of the cases. One hundred and eighty patients had two or more mutations. Occasionally a predominant phenotype masked the presence of a second abnormality. One hundred and sixteen patients presented with mutations that had previously been associated with an increased VWF clearance. Ristocetin induced platelet agglutination (RIPA) unavailability, central phenotypic results disagreement and difficult distinction between severe type 1 and type 3 VWD prevented a clear diagnosis in 74 patients. A local/central disagreement over diagnosis occurred in 42.3% of the whole cohort. The NGS study facilitated an appropriate classification in 60 of them. Based on these results, a proposal for a change in the VWD diagnostic paradigm, suggesting the inclusion of the analysis of VWF at the initial diagnostic process, has been made. An extension of this project to include 400 new VWD patients has begun. A diagnostic strategy has been developed, and a Spanish consensus guideline for optimal treatment of VWD was developed in Spain. Desmopressin (DDAVP) is the treatment of choice in responsive VWD patients. VWF concentrates (VWF/FVIII) are used in individuals unresponsive to DDAVP, when DDAVP is contraindicated, or in VWD types 2B and 3, and for long term management needs (e.g., post major surgery).},
issn = {2521-361X}, url = {https://aob.amegroups.org/article/view/4264}
}