Molecular and clinical profile of von Willebrand disease in Spain (PCM–EVW–ES): Proposal for a new diagnostic paradigm

Javier Batlle; Almudena Pérez-Rodríguez; Irene Corrales; María Fernanda López-Fernández; Ángela Rodríguez-Trillo; Esther Lourés; Ana Rosa Cid; Santiago Bonanad; Noelia Cabrera; Andrés Moret; Rafael Parra; María Eva Mingot-Castellano; Ignacia Balda; Carmen Altisent; Rocío Pérez-Montes; Rosa María Fisac; Gemma Iruín; Sonia Herrero; Inmaculada Soto; Beatriz de Rueda; Víctor Jiménez-Yuste; Nieves Alonso; Dolores Vilariño; Olga Arija; Rosa Campos; María José Paloma; Nuria Bermejo; Teresa Toll; José Mateo; Karmele Arribalzaga; Pascual Marco; Ángeles Palomo; Lizheidy Sarmiento; Belén Iñigo; María del Mar Nieto; Rosa Vidal; María Paz Martínez; Reyes Aguinaco; Jesús María César; María Ferreiro; Javier García-Frade; Ana María Rodríguez-Huerta; Jorge Cuesta; Ramón Rodríguez-González; Faustino García-Candel; Rosa Cornudella; Carlos Aguilar; Nina Borràs; Francisco Vidal

doi:10.1160/TH15-04-0282

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2016; 115(01): 40-50
DOI: 10.1160/TH15-04-0282

Coagulation and Fibrinolysis

Schattauer GmbH Schattauer

Molecular and clinical profile of von Willebrand disease in Spain (PCM–EVW–ES): Proposal for a new diagnostic paradigm

Javier Batlle

¹Complexo Hospitalario Universitario A Coruña, INIBIC, A Coruña, Spain

,

Almudena Pérez-Rodríguez

¹Complexo Hospitalario Universitario A Coruña, INIBIC, A Coruña, Spain

,

Irene Corrales

²Banc de Sang i Teixits, Barcelona, Spain

,

María Fernanda López-Fernández

¹Complexo Hospitalario Universitario A Coruña, INIBIC, A Coruña, Spain

,

Ángela Rodríguez-Trillo

¹Complexo Hospitalario Universitario A Coruña, INIBIC, A Coruña, Spain

,

Esther Lourés

¹Complexo Hospitalario Universitario A Coruña, INIBIC, A Coruña, Spain

,

Ana Rosa Cid

³Hospital Universitario y Politécnico La Fe, Valencia, Spain

,

Santiago Bonanad

³Hospital Universitario y Politécnico La Fe, Valencia, Spain

,

Noelia Cabrera

³Hospital Universitario y Politécnico La Fe, Valencia, Spain

,

Andrés Moret

³Hospital Universitario y Politécnico La Fe, Valencia, Spain

,

Rafael Parra

²Banc de Sang i Teixits, Barcelona, Spain

⁴Hospital Universitari Vall d’Hebron, Barcelona, Spain

,

María Eva Mingot-Castellano

⁵Hospital Regional Universitario de Málaga, Málaga, Spain

,

Ignacia Balda

⁶Hospital Universitario Dr. Negrín, Las Palmas de Gran Canaria, Spain

,

Carmen Altisent

⁴Hospital Universitari Vall d’Hebron, Barcelona, Spain

,

Rocío Pérez-Montes

⁷Hospital Universitario Marqués de Valdecilla, Santander, Spain

,

Rosa María Fisac

⁸Salud Castilla y León, Segovia, Spain

,

Gemma Iruín

⁹Hospital Universitario Cruces, Barakaldo, Spain

,

Sonia Herrero

¹⁰Hospital Universitario de Guadalajara, Guadalajara, Spain

,

Inmaculada Soto

¹¹Hospital Universitario Central de Asturias, Oviedo, Spain

,

Beatriz de Rueda

¹²Hospital Universitario Miguel Servet, Zaragoza, Spain

,

Víctor Jiménez-Yuste

¹³Hospital Universitario La Paz, Madrid, Spain

,

Nieves Alonso

¹⁴Hospital Infanta Cristina, Badajoz, Spain

,

Dolores Vilariño

¹⁵Complexo Hospitalario Universitario Santiago de Compostela, Spain

,

Olga Arija

¹⁶Hospital Universitario Lucus Augusti, Lugo, Spain

,

Rosa Campos

¹⁷Hospital Jerez de la Frontera, Cádiz, Spain

,

María José Paloma

¹⁸Hospital Virgen del Camino, Pamplona, Spain

,

Nuria Bermejo

¹⁹Hospital San Pedro de Alcántara, Cáceres, Spain

,

Teresa Toll

²⁰Hospital Sant Joan de Deu, Barcelona, Spain

,

José Mateo

²¹Hospital Sta Creu i St Pau, Barcelona, Spain

,

Karmele Arribalzaga

²²Hospital Universitario Fundación Alcorcón, Madrid, Spain

,

Pascual Marco

²³Hospital General de Alicante, Alicante, Spain

,

Ángeles Palomo

⁵Hospital Regional Universitario de Málaga, Málaga, Spain

,

Lizheidy Sarmiento

²⁴Hospital Universitario 12 de Octubre, Madrid, Spain

,

Belén Iñigo

²⁵Hospital Clínico San Carlos, Madrid, Spain

,

María del Mar Nieto

²⁶Complejo Hospitalario de Jaén, Jaén, Spain

,

Rosa Vidal

²⁷Fundación Jiménez Díaz, Madrid, Spain

,

María Paz Martínez

²⁸Hospital Nuestra Sra. de Sonsoles, Ávila, Spain

,

Reyes Aguinaco

²⁹Hospital Joan XXIII, Tarragona, Spain

,

Jesús María César^†

³⁰Hospital Ramón y Cajal, Madrid, Spain

,

María Ferreiro

³¹Hospital Montecelo, Pontevedra, Spain

,

Javier García-Frade

³²Hospital Río Hortega, Valladolid, Spain

,

Ana María Rodríguez-Huerta

³³Hospital Gregorio Marañón, Madrid, Spain

,

Jorge Cuesta

³⁴Hospital Virgen de la Salud, Toledo, Spain

,

Ramón Rodríguez-González

³⁵Hospital Severo Ochoa, Madrid, Spain

,

Faustino García-Candel

³⁶Hospital Universitario Virgen Arrixaca, Murcia, Spain

,

Rosa Cornudella

³⁷Hospital Lozano Blesa, Zaragoza, Spain

,

Carlos Aguilar

³⁸Hospital Santa Bárbara, Soria, Spain

,

Nina Borràs

²Banc de Sang i Teixits, Barcelona, Spain

,

Francisco Vidal

²Banc de Sang i Teixits, Barcelona, Spain

› Institutsangaben

Abstract

Summary

The diagnosis of von Willebrand disease (VWD) remains difficult in a significant proportion of patients. A Spanish multicentre study investigated a cohort of 556 patients from 330 families who were analysed centrally. VWD was confirmed in 480. Next generation sequencing (NGS) of the whole coding VWF was carried out in all recruited patients, compared with the phenotype, and a final diagnosis established. A total of 238 different VWF mutations were found, 154 were not included in the Leiden Open Variation Database (LOVD). Of the patients, 463 were found to have VWF mutation/s. A good phenotypic/ genotypic association was estimated in 96.5 % of the patients. One hundred seventy-four patients had two or more mutations. Occasionally a predominant phenotype masked the presence of a second abnormality. One hundred sixteen patients presented with mutations that had previously been associated with increased von Willebrand factor (VWF) clearance. RIPA unavailability, central phenotypic results disagreement and difficult distinction between severe type 1 and type 3 VWD prevented a clear diagnosis in 70 patients. The NGS study facilitated an appropriate classification in 63 of them. The remaining seven patients presented with a VWF novel mutation pending further investigation. In five patients with a type 3 and two with a type 2A or 2B phenotype with no mutation, an acquired von Willebrand syndrome (AVWS) was suspected/confirmed. These data seem to support NGS as a first line efficient and faster paradigm in VWD diagnosis.

Supplementary Material to this article is available online at www.thrombosis-online.com.

Keywords

VWD - VWF - NGS - phenotype - genotype

Volltext

Referenzen

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