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CC BY 4.0 · TH Open 2022; 06(04): e335-e346
DOI: 10.1055/s-0042-1757635
Original Article

Analysis of von Willebrand Disease in the “Heart of Europe”

Inge Vangenechten
1   Haemostasis Unit, Antwerp University Hospital, Edegem, Belgium
2   Medicine and Health Sciences, Haemostasis Research Unit, Antwerp University, Antwerp, Belgium
3   Antwerp University, Antwerp, Belgium
,
Petr Smejkal
4   Department of Clinical Haematology, University Hospital Brno, Brno, Czech Republic
5   Department of Laboratory Methods, Faculty of Medicine, Masaryk University, Brno, Czech Republic
,
Jiri Zavrelova
4   Department of Clinical Haematology, University Hospital Brno, Brno, Czech Republic
5   Department of Laboratory Methods, Faculty of Medicine, Masaryk University, Brno, Czech Republic
,
Ondrej Zapletal
6   Department of Pediatric Haematology, University Hospital Brno, Brno, Czech Republic
,
Alexander Wild
7   Department of Haematology, University F. D. Roosevelt Hospital, Banská Bystrica, Slovakia
,
Jan Jacques Michiels
8   Blood Coagulation and Vascular Medicine Center, Goodheart Institute & Foundation in Nature Medicine, Rotterdam, The Netherlands
,
Zwi Berneman
3   Antwerp University, Antwerp, Belgium
9   Department of Haematology, Antwerp University Hospital, Edegem, Belgium
,
Jan Blatny
6   Department of Pediatric Haematology, University Hospital Brno, Brno, Czech Republic
,
Angelika Batorova
10   National Hemophilia Center, Department of Haematology and Blood Transfusion of the Medical School of the Comenius University, Bratislava, Slovakia
,
Tatiana Prigancova
10   National Hemophilia Center, Department of Haematology and Blood Transfusion of the Medical School of the Comenius University, Bratislava, Slovakia
,
Miroslav Penka
4   Department of Clinical Haematology, University Hospital Brno, Brno, Czech Republic
5   Department of Laboratory Methods, Faculty of Medicine, Masaryk University, Brno, Czech Republic
,
Alain Gadisseur
1   Haemostasis Unit, Antwerp University Hospital, Edegem, Belgium
2   Medicine and Health Sciences, Haemostasis Research Unit, Antwerp University, Antwerp, Belgium
3   Antwerp University, Antwerp, Belgium
9   Department of Haematology, Antwerp University Hospital, Edegem, Belgium
› Author Affiliations Funding This study was supported and financed by an unrestricted grant from Bayer Health Care, Belgium and CSL Behring, Belgium.
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Abstract

Background von Willebrand disease (VWD) is a genetic bleeding disorder caused by defects of von Willebrand factor (VWF), quantitative (type 1 and 3) or qualitative (type 2). The laboratory phenotyping is heterogenic making diagnosis difficult.

Objectives Complete laboratory analysis of VWD as an expansion of the previously reported cross-sectional family-based VWD study in the Czech Republic (BRNO-VWD) and Slovakia (BRA-VWD) under the name “Heart of Europe,” in order to improve the understanding of laboratory phenotype/genotype correlation.

Patients and Methods In total, 227 suspected VWD patients were identified from historical records. Complete laboratory analysis was established using all available assays, including VWF multimers and genetic analysis.

Results A total of 191 patients (from 119 families) were confirmed as having VWD. The majority was characterized as a type 1 VWD, followed by type 2. Multimeric patterns concordant with laboratory phenotypes were found in approximately 83% of all cases. A phenotype/genotype correlation was present in 84% (77% type 1, 99% type 2, and 61% type 3) of all patients. Another 45 candidate mutations (23 novel variations), not found in the initial study, could be identified (missense 75% and truncating 24%). An exon 1–3 gene deletion was identified in 14 patients where no mutation was found by direct DNA sequencing, increasing the linkage up to 92%, overall.

Conclusion This study provides a cross-sectional overview of the VWD population in a part of Central Europe. It is an addition to the previously published BRNO-VWD study, and provides important data to the International Society of Thrombosis and Haemostasis/European Association for Haemophilia and Allied Disorders VWD mutation database with identification of novel causal mutations.

Keywords

classification - genotype - phenotype - von Willebrand disease - von Willebrand factor

Addendum

A.G., J.J.M, P.S., and A.B. were responsible for the study initiation. O.Z., P.S., A.B., T.P., and A.W. were responsible for the sample collection. I.V. was involved in study design, data collection, and performing laboratory analysis. I.V. and A.G. were responsible for analysis and interpretation of results and performed statistical analysis. I.V. was the lead author of the initial manuscript. A.G., J.B., J.Z., M.P., O.Z., P.S., and A.B were responsible for revisions of the draft manuscripts. A.G. was responsible for review and approval of the final manuscript for submission.


Disclosure of Conflict of Interest

The authors declare that there are no conflicts of interest.


Supplementary Material



Publication History

Received: 09 June 2022

Accepted: 16 August 2022

Article published online:
19 October 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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