Analysis of von Willebrand Disease in the “Heart of Europe”
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 VW...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Georg Thieme Verlag KG
2022-10-01
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| Series: | TH Open |
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| Online Access: | http://www.thieme-connect.de/DOI/DOI?10.1055/s-0042-1757635 |
| _version_ | 1798027929602490368 |
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| author | Inge Vangenechten Petr Smejkal Jiri Zavrelova Ondrej Zapletal Alexander Wild Jan Jacques Michiels Zwi Berneman Jan Blatny Angelika Batorova Tatiana Prigancova Miroslav Penka Alain Gadisseur |
| author_facet | Inge Vangenechten Petr Smejkal Jiri Zavrelova Ondrej Zapletal Alexander Wild Jan Jacques Michiels Zwi Berneman Jan Blatny Angelika Batorova Tatiana Prigancova Miroslav Penka Alain Gadisseur |
| author_sort | Inge Vangenechten |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T18:59:44Z |
| format | Article |
| id | doaj.art-75dd3755ee8443b3a845469109e1de0d |
| institution | Directory Open Access Journal |
| issn | 2512-9465 |
| language | English |
| last_indexed | 2024-04-11T18:59:44Z |
| publishDate | 2022-10-01 |
| publisher | Georg Thieme Verlag KG |
| record_format | Article |
| series | TH Open |
| spelling | doaj.art-75dd3755ee8443b3a845469109e1de0d2022-12-22T04:08:05ZengGeorg Thieme Verlag KGTH Open2512-94652022-10-010604e335e34610.1055/s-0042-1757635Analysis of von Willebrand Disease in the “Heart of Europe”Inge Vangenechten0Petr Smejkal1Jiri Zavrelova2Ondrej Zapletal3Alexander Wild4Jan Jacques Michiels5Zwi Berneman6Jan Blatny7Angelika Batorova8Tatiana Prigancova9Miroslav Penka10Alain Gadisseur11Haemostasis Unit, Antwerp University Hospital, Edegem, BelgiumDepartment of Clinical Haematology, University Hospital Brno, Brno, Czech RepublicDepartment of Clinical Haematology, University Hospital Brno, Brno, Czech RepublicDepartment of Pediatric Haematology, University Hospital Brno, Brno, Czech RepublicDepartment of Haematology, University F. D. Roosevelt Hospital, Banská Bystrica, SlovakiaBlood Coagulation and Vascular Medicine Center, Goodheart Institute & Foundation in Nature Medicine, Rotterdam, The NetherlandsAntwerp University, Antwerp, BelgiumDepartment of Pediatric Haematology, University Hospital Brno, Brno, Czech RepublicNational Hemophilia Center, Department of Haematology and Blood Transfusion of the Medical School of the Comenius University, Bratislava, SlovakiaNational Hemophilia Center, Department of Haematology and Blood Transfusion of the Medical School of the Comenius University, Bratislava, SlovakiaDepartment of Clinical Haematology, University Hospital Brno, Brno, Czech RepublicHaemostasis Unit, Antwerp University Hospital, Edegem, BelgiumBackground 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.http://www.thieme-connect.de/DOI/DOI?10.1055/s-0042-1757635classificationgenotypephenotypevon willebrand diseasevon willebrand factor |
| spellingShingle | Inge Vangenechten Petr Smejkal Jiri Zavrelova Ondrej Zapletal Alexander Wild Jan Jacques Michiels Zwi Berneman Jan Blatny Angelika Batorova Tatiana Prigancova Miroslav Penka Alain Gadisseur Analysis of von Willebrand Disease in the “Heart of Europe” TH Open classification genotype phenotype von willebrand disease von willebrand factor |
| title | Analysis of von Willebrand Disease in the “Heart of Europe” |
| title_full | Analysis of von Willebrand Disease in the “Heart of Europe” |
| title_fullStr | Analysis of von Willebrand Disease in the “Heart of Europe” |
| title_full_unstemmed | Analysis of von Willebrand Disease in the “Heart of Europe” |
| title_short | Analysis of von Willebrand Disease in the “Heart of Europe” |
| title_sort | analysis of von willebrand disease in the heart of europe |
| topic | classification genotype phenotype von willebrand disease von willebrand factor |
| url | http://www.thieme-connect.de/DOI/DOI?10.1055/s-0042-1757635 |
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