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Thromb Haemost 2019; 119(04): 594-605
DOI: 10.1055/s-0039-1678528
Coagulation and Fibrinolysis
Georg Thieme Verlag KG Stuttgart · New York

Analysis of von Willebrand Disease in the South Moravian Population (Czech Republic): Results from the BRNO-VWD Study

Inge Vangenechten
1   Haemostasis Unit, Antwerp University Hospital, Edegem, Belgium
2   Haemostasis Research Unit, University of Antwerp, Antwerp, Belgium
3   CSL Behring Chair in von Willebrand Disease, University of Antwerp, 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
,
Ondrej Zapletal
6   Department of Pediatric Haematology, University Hospital Brno, Brno, Czech Republic
,
Jan Jacques Michiels
7   Blood Coagulation and Vascular Medicine Center, Goodheart Institute and Foundation in Nature Medicine, Rotterdam, The Netherlands
,
Zwi Berneman
3   CSL Behring Chair in von Willebrand Disease, University of Antwerp, Antwerp, Belgium
8   Department of Haematology, Antwerp University Hospital, Edegem, Belgium
,
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
,
Jan Blatný
6   Department of Pediatric Haematology, University Hospital Brno, Brno, Czech Republic
,
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   Haemostasis Research Unit, University of Antwerp, Antwerp, Belgium
3   CSL Behring Chair in von Willebrand Disease, University of Antwerp, Antwerp, Belgium
8   Department of Haematology, Antwerp University Hospital, Edegem, Belgium
› Institutsangaben Funding This study was supported and financed by an unrestricted grant from Bayer Health Care, Belgium.
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Publikationsverlauf

09. Juli 2018

12. Dezember 2018

Publikationsdatum:
05. Februar 2019 (online)

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Abstract

Background von Willebrand disease (VWD) is an inherited bleeding disorder caused by a quantitative (type 1 and 3) or qualitative (type 2) defect of von Willebrand factor (VWF). The heterogeneity of laboratory phenotyping makes diagnosing difficult.

Objective A cross-sectional, family-based VWD study in a collaboration between University Hospital Brno (Czech Republic) and Antwerp University Hospital (Belgium) to improve the understanding of laboratory phenotype/genotype correlation.

Patients and Methods A total of 205 patients with suspected VWD were identified from historical records. Complete laboratory analysis was established using all available VWD assays including VWF multimers and genetic analysis.

Results Based on the current International Society of Thrombosis and Haemostasis (ISTH) – Scientific and Standardization Committee VWD classification and type 2A sub-division into 2A/IIA, IID, IIC and IIE, the majority was characterized as a type 1 VWD, followed by type 2. Proposed laboratory phenotypes were confirmed by their multimeric pattern within 98% of this cohort. All type 2, 3 and 75% of type 1 VWD patients were confirmed by underlying causative mutations. Forty-six different causal mutations (117 not previously described in the literature) could be identified. Fifty per cent of all cases was represented by eight individual mutations, mainly p.Pro812ArgfsX31. Thirteen patients had a large heterozygous gene alteration.

Conclusion Although an extensive panel of tests was used, VWD classification and (sub)typing remains difficult and fluid. This study provides a cross-sectional overview of the VWD population in the Czech Republic and provides important data to the ISTH/European Association for Haemophilia and Allied Disorders VWD mutation database in linking causal mutations with unique VWD (sub)types. It also identifies new, as not previously described in the literature, causal mutations.

Keywords

classification - mutations - von Willebrand disease - von Willebrand factor - von Willebrand factor assays

Authors' Contributions

A.G., J.J.M. and P.S. were responsible for the study initiation. O.Z. and P.S. 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.J.M. J.Z., M.P., O.Z. and P.S. were responsible for revisions of the draft manuscripts. A.G. was responsible for review and approval of the final manuscript for submission.


Supplementary Material

 

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