Molecular and Clinical Profile of Von Willebrand Disease in Spain

Study Overview
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Brief Summary
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The present Project is a third phase of the previous PCM-EVW-ES Project (Batlle et al. Thromb & Haemost 2015) with the aim of its extension, further analysis with an innovation development in the field of von Willebrand disease (VWD) based in the newer recently available methodologies. The aim of this project is to help the physician in a more uniform characterization and therapy of VWD in clinical practice, at an international level. A reduction of the expenses in the diagnosis process by using the new methodologies is pursued.

Detailed Description
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The present Project is a third phase of the previous PCM-EVW-ES Project (Batlle et al. Thromb & Haemost 2015) with the aim of its extension, further analysis with an innovation development in the field of von Willebrand disease (VWD) based in the newer recently available methodologies. The aim of this project is to help the physician in a more uniform characterization and therapy of VWD in clinical practice, at an international level. A reduction of the expenses in the diagnosis process by using the new methodologies is pursued. The specific objectives and corresponding tasks of the present project are as follows: 1. Extension of the central phenotypic and next generation sequencing (NGS) genotypic characterization of the VWD in Spain, through the prospective recruitment in the Spanish VWD cohort of approximately 500 new patients with local historical VWD diagnosis (from approximately 38 centres). i. Improvement of the registry portal and database. ii. Recruitment criteria, phenotypic and genetic analysis of new recruited patients. In silico studies of novel von Willebrand factor gene (VWF) mutations iii. Analysis/investigation of the potential interrelationship between different clinical, phenotypic and genetic variations of the all recruited patients. iv. Validation/confirmation of the PCM-EVW-ES of the new initial diagnostic proposed algorithm including VWF NGS analysis. This project involves leading innovation and translational research with a direct impact on the quality of clinical care (applicability). To our knowledge there is no similar project in this field. Potential patents may derive from this project. It involves also development of e-learning and new information technologies (debates forum, ads, google search engine). This project may promote international collaboration. Development of an algorithmic platform that facilitates diagnosis and therapy orientation of VWD in clinical practice using the selected data from the overwhelming amount of information that new technologies, such as NGS, are producing.

Official Title
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Molecular and Clinical Profile of Von Willebrand Disease (VWD) in Spain (PCM-EVW-ES). Recruitment Extension, Further Data Analysis, Improvement of Registry Platform, Diagnosis and Management of VWD Application Development

Conditions
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Von Willebrand Disease

Intervention / Treatment
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* Genetic: VWF gene analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: One or more of the following: VWF ≤ 30 IU/d, in 2 or more occasions. Presence of multimeric abnormalities. If isolated FVIII deficiency demonstration of decreased FVIII binding. Presence of some VWF mutation. ↑ RIPA at low concentrations of ristocetin. Exclusion Criteria: Presence of any data suggesting AVWS. Absence of a signed patient informed consent

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| VWD Spanish Cohort<br>Patients with previously diadnosis of VWD from approximately 38-40 different centers from Spain. Samples from these patients will be analyzed locally, and also centrally for VWF and VWFgene | Genetic: VWF gene analysis<br>* 52 exons adjacent intronic regions and promotor of VWF will be analyzed<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Central diagnosis of 400 new VWD Spanish patients | Phenotype and genetic central diagnosis of 400 new VWD Spanish patients. With determinations in samples obtained after patients recruitment, VWF NGS sequencing carried out in all patients, for exons 1 to 52, adjacent intronic regions and aproximately 1300 bp of promotor region. A pheno-genotype will be made With a final diagnosis assignment Evaluation of pheno/genotype congruence | January 2019 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PCM-EVW-ES project algorithm validation/confirmation | Evaluation of the algorithm with data from the Spanish Registry patients. Mutation results will be used in the first line of VWD diagnosis Correlation between mutations and phenotype | January 2019 | 
| Potential collaboration with the International Society on Thrombosis and Haemostasis | Proposal for evaluation of the PCM-EVW-ES algorithm with data from other international VWD patients cohorts | January 2019 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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von Willebrand disease (VWD), von Willebrand factor (VWF), von Willebrand factor gene, next generation sequencing, diagnosis, VWD Spanish Cohort