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

Inge Vangenechten; Petr Smejkal; Ondrej Zapletal; Jan Jacques Michiels; Zwi Berneman; Jiri Zavrelova; Jan Blatný; Miroslav Penka; Alain Gadisseur

doi:10.1055/s-0039-1678528

Thrombosis and Haemostasis, Table of Contents

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

¹Haemostasis Unit, Antwerp University Hospital, Edegem, Belgium

²Haemostasis Research Unit, University of Antwerp, Antwerp, Belgium

³CSL Behring Chair in von Willebrand Disease, University of Antwerp, Antwerp, Belgium

,

Petr Smejkal

⁴Department of Clinical Haematology, University Hospital Brno, Brno, Czech Republic

⁵Department of Laboratory Methods, Faculty of Medicine, Masaryk University, Brno, Czech Republic

,

Ondrej Zapletal

⁶Department of Pediatric Haematology, University Hospital Brno, Brno, Czech Republic

,

Jan Jacques Michiels

⁷Blood Coagulation and Vascular Medicine Center, Goodheart Institute and Foundation in Nature Medicine, Rotterdam, The Netherlands

,

Zwi Berneman

³CSL Behring Chair in von Willebrand Disease, University of Antwerp, Antwerp, Belgium

⁸Department of Haematology, Antwerp University Hospital, Edegem, Belgium

,

Jiri Zavrelova

⁴Department of Clinical Haematology, University Hospital Brno, Brno, Czech Republic

⁵Department of Laboratory Methods, Faculty of Medicine, Masaryk University, Brno, Czech Republic

,

Jan Blatný

⁶Department of Pediatric Haematology, University Hospital Brno, Brno, Czech Republic

,

Miroslav Penka

⁴Department of Clinical Haematology, University Hospital Brno, Brno, Czech Republic

⁵Department of Laboratory Methods, Faculty of Medicine, Masaryk University, Brno, Czech Republic

,

Alain Gadisseur

¹Haemostasis Unit, Antwerp University Hospital, Edegem, Belgium

²Haemostasis Research Unit, University of Antwerp, Antwerp, Belgium

³CSL Behring Chair in von Willebrand Disease, University of Antwerp, Antwerp, Belgium

⁸Department of Haematology, Antwerp University Hospital, Edegem, Belgium

› Author Affiliations

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

Full Text

References

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Supplementary Material