OC 63.5 - Update on the VWD Clinical and Molecular Profile Project in Spain (PCM-EVW-ES): outcomes from the second recruitment phase

Tuesday, June 25, 2024

15:45 – 16:00 ICT

Room: Ballroom B3

Presenting Author(s)

NB

Nina Borràs

PhD
Laboratori de Coagulopaties Congènites, Banc de Sang i Teixits, Barcelona, Spain
Barcelona, Catalonia, Spain

Co-Author(s)

AP

Almudena Pérez-Rodríguez

PhD
3. Servicio de Hematología, Complexo Hospitalario Universitario A Coruña, INIBIC, A Coruña, Spain.
A Coruña, Galicia, Spain
ML

María F. López-Fernández

PhD MD
Servicio de Hematología, Complexo Hospitalario Universitario A Coruña, INIBIC, A Coruña, Spain
La Coruña, Galicia, Spain
AC

Ana Cid

PhD MD
4. Servicio de Hematología, Hospital Universitario Politécnico La Fe, Valencia, Spain
Valencia, Comunidad Valenciana, Spain
MM

Mingot Maria Eva

5. Servicio de Hematología, Hospital Universitario Virgen del Rocío, Sevilla, Spain
PhD MD
Sevilla, Andalucia, Spain
María Teresa Alvarez-Román, MD, PhD

Head of the Haemostasis Unit
Department of Hematology, University Hospital La Paz, Autonoma University of Madrid, Madrid, Spain
Madrid, Madrid, Spain
IG

Iris Garcia-Martínez

PhD
Banc de Sang i Teixits, Vall d'Hebron Research Institute (VHIR-UAB), Barcelona, Spain.
Barcelona, Catalonia, Spain
FB

Francisco Javier Batlle

PhD MD
3. Servicio de Hematología, Complexo Hospitalario Universitario A Coruña, INIBIC, A Coruña, Spain.
A Coruña, Galicia, Spain
FV

Francisco Vidal

Head of Unit, PhD
Laboratori de Coagulopaties Congènites, Banc de Sang i Teixits, Barcelona, Spain
Barcelona, Catalonia, Spain
MG

Maria del Carmen Gómez del Castillo

PhD MD
3. Servicio de Hematología, Complexo Hospitalario Universitario A Coruña, INIBIC, A Coruña, Spain
A Coruña, Catalonia, Spain
IC

Irene Corrales

Main researcher, PhD
Laboratori de Coagulopaties Congènites, Banc de Sang i Teixits, Barcelona, Spain
Barcelona, Catalonia, Spain

Background: The Clinical and Molecular Profile of von Willebrand Disease (VWD) in Spain (PCM-EVW-ES) project, initiated in 2010, aims to characterize the phenotype and genotype of individuals diagnosed with VWD. The first phase, enrolling 556 individuals, allowed the identification of 480 patients with definitive VWD diagnosis. Following its success, a second phase was approved in 2016 to expand the registry.

Aims: To delineate the phenotypic and molecular characteristics of patients enrolled in the PCM-EVW-ES second phase, emphasizing the role of molecular genetics.

Methods: A total of 334 patients (253 families) were recruited from 42 Spanish hospitals. Laboratory tests (including VWF:Ag, VWF:RCo, FVIII:C, VWF:CB, VWF:FVIIIB and the multimeric pattern) and molecular analysis were performed centrally. VWF analysis was approached using microfluidics technology and Illumina sequencing (MiSeq). MLPA was used to identify structural variants.

Results: A definitive VWD diagnosis was established in 250 (74.8%) patients with the following distribution: 44% of type 1, 8.4% of type 3, 36.8% of type 2 and 10.8% remain unclassified (Figure 1). Candidate mutations were identified in all patients except 5 (4 type 1 and 1 type 2A/2B). Genetic analysis identified 342 variants (149 different) allowing an accurate diagnosis in 90 patients that would be misdiagnosed (n=51) or excluded (n=39) by laboratory results. Additional 84 patients were finally excluded due to failure to meet the inclusion criteria (n=73), hemophilia A misdiagnosis (n=6) or acquired syndrome (n=5).

Conclusion(s): The PCM-EVW-ES is one of the largest VWD cohort accounting for 734 patients with a well-established genotype-phenotype correlation. Centralized analysis of molecular and laboratory data enable us to obtain a clear picture of the VWD in our country and has demonstrated the value of molecular VWF analysis to establish a definitive diagnosis.

MINECO-FIS-ISCIII (PI12/01494, PI15/01643 y RD12/0042/0053). Baxter-Baxalta (H13–000845); Shire (H16-32544).