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PLoS One. 2018 Jun 20;13(6):e0197876. doi: 10.1371/journal.pone.0197876. eCollection 2018.

Role of multimeric analysis of von Willebrand factor (VWF) in von Willebrand disease (VWD) diagnosis: Lessons from the PCM-EVW-ES Spanish project.

Author information

1
Servicio Hematología, Complexo Hospitalario Universitario A Coruña, INIBIC, A Coruña, Spain.
2
Banc de Sang i Teixits, Barcelona, Spain.
3
Unitat d'Hemofilia, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona (VHIR-UAB), Barcelona, Spain.
4
Servicio Hematología, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
5
Servicio Hematología, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
6
Servicio Hematología, Hospital Regional Universitario de Málaga, Málaga, Spain.
7
Servicio Hematología, Hospital Universitario Dr. Negrín, Las Palmas de Gran Canaria, Spain.
8
Servicio Hematología, Hospital Universitario Marqués de Valdecilla, Santander, Spain.
9
Servicio Hematología, Salud Castilla y León, Segovia, Spain.
10
Servicio Hematología, Hospital Universitario Cruces, Barakaldo, Spain.
11
Servicio Hematología, Hospital Universitario de Guadalajara, Guadalajara, Spain.
12
Servicio Hematología, Hospital Universitario Central de Asturias, Oviedo, Spain.
13
Servicio Hematología, Hospital Universitario Miguel Servet, Zaragoza, Spain.
14
Servicio Hematología, Hospital Universitario La Paz, Madrid, Spain.
15
Servicio Hematología, Hospital Infanta Cristina, Badajoz, Spain.
16
Servicio Hematología, Complexo Hospitalario Universitario Santiago de Compostela, Spain.
17
Servicio Hematología, Hospital Universitario Lucus Augusti, Lugo, Spain.
18
Servicio Hematología, Hospital Jerez de la Frontera, Cádiz, Spain.
19
Servicio Hematología, Hospital Virgen del Camino, Pamplona, Spain.
20
Servicio Hematología, Hospital San Pedro de Alcántara, Cáceres, Spain.
21
Servicio Hematología, Hospital Sant Joan de Deu, Barcelona, Spain.
22
Servicio Hematología, Hospital Sta Creu i St Pau, Barcelona, Spain.
23
Servicio Hematología, Hospital Universitario Fundación Alcorcón, Madrid, Spain.
24
Servicio Hematología, Hospital General de Alicante, Alicante, Spain.
25
Servicio Hematología, Hospital Universitario 12 de Octubre, Madrid, Spain.
26
Servicio Hematología, Hospital Clínico San Carlos, Madrid, Spain.
27
Servicio Hematología, Complejo Hospitalario de Jaén, Jaén, Spain.
28
Servicio Hematología, Fundación Jiménez Díaz, Madrid, Spain.
29
Servicio Hematología, Hospital Nuestra Sra. de Sonsoles, Ávila, Spain.
30
Servicio Hematología, Hospital Joan XXIII, Tarragona, Spain.
31
Servicio Hematología, Hospital Ramón y Cajal, Madrid, Spain.
32
Servicio Hematología, Hospital Montecelo, Pontevedra, Spain.
33
Servicio Hematología, Hospital Río Hortega, Valladolid, Spain.
34
Servicio Hematología, Hospital Gregorio Marañón, Madrid, Spain.
35
Servicio Hematología, Hospital Virgen de la Salud, Toledo, Spain.
36
Servicio Hematología, Hospital Severo Ochoa, Madrid, Spain.
37
Servicio Hematología, Hospital Universitario Virgen Arrixaca, Murcia, Spain.
38
Servicio Hematología, Hospital Lozano Blesa, Zaragoza, Spain.
39
Servicio Hematología, Hospital Santa Bárbara, Soria, Spain.
40
Department of Research, Lapisoft Project S.L., A Coruña, Spain.
41
CIBER de Enfermedades Cardiovasculares (CIBERCV), Barcelona, Spain.

Abstract

The multimeric analysis (MA) of plasma von Willebrand factor (VWF) evaluates structural integrity and helps in the diagnosis of von Willebrand disease (VWD). This assay is a matter of controversy, being considered by some investigators cumbersome and only slightly informative. The centralised study 'Molecular and Clinical Profile of von Willebrand Disease in Spain (PCM-EVW-ES)' has been carried out by including the phenotypic assessment and the genetic analysis by next generation sequencing (NGS) of the VWF gene (VWF). The aim of the present study was to evaluate the role of MA to the diagnosis of these patients and their potential discrepancies. Two hundred and seventy out of 480 patients centrally diagnosed with VWD had normal multimers, 168 had abnormal multimers and 42 a total absence of multimers. VWF MA was of great significance in the diagnosis of 83 patients (17.3%), it was also of help in the diagnosis achieved in 365 additional patients (76%) and was not informative in 32 cases (6.7%). With regard to discrepancies, 110 out of 480 (23%) patients centrally diagnosed with VWD presented some kind of discordance between VWF:RCo/VWF:Ag and/or VWF:CB/VWF:Ag ratios, multimeric study and/or genetic results. The VWF MA was key in the presence of novel mutations as well as in cases with phenotypic discrepancies. A comparison between the contribution of MA and VWF:CB showed a clearly higher contribution of the former in the diagnostic process. These data seem to reinforce the relevance of the VWF MA in VWD diagnosis, despite all its limitations.

PMID:
29924855
PMCID:
PMC6010290
DOI:
10.1371/journal.pone.0197876
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

The authors have declared that no competing interests exist. The funders provided support but did not have any additional role in study design, data collection and analysis, decision to publish, or preparation of the manuscript, as well as they do not alter our adherence to PLOS ONE policies on sharing data and materials. The only implication in the study of the funding organizations was to provide financial support for the development of the project (sample collection and shipment and for research materials). The Project “Molecular and Clinical Profile of VWD in Spain (PCM-EVW-ES) SPANISH REGISTRY” has been registered at www.clinicaltrials.gov Protocol Registration and Results System. (Study: Identifier: NCT02869074RE. Responsible Party Francisco Javier Batlle Fonrodona). Affiliation: Spanish Society on Thrombosis and Haemostasis (SETH). Last Public Release: 10/03/2017. The Banc de Sang i Teixits (Blood and Tissue Bank) is a public agency of the Catalan Department of Health. For more information you can visit the web page: https://www.bancsang.net/info-corporativa/en_missio/.

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