Genetic Variants, Thrombocytopenia and Clinical Phenotype of type 2B von Willebrand Disease: a median 16-year follow-up study.

Desmopressin Genotype Pregnancy Thrombocytopenia Von Willebrand Disease

Journal

Journal of thrombosis and haemostasis : JTH
ISSN: 1538-7836
Titre abrégé: J Thromb Haemost
Pays: England
ID NLM: 101170508

Informations de publication

Date de publication:
27 Sep 2024
Historique:
received: 21 03 2024
revised: 05 08 2024
accepted: 14 08 2024
medline: 30 9 2024
pubmed: 30 9 2024
entrez: 29 9 2024
Statut: aheadofprint

Résumé

Type 2B Von Willebrand disease (VWD) is a bleeding disorder caused by gain-of-function variants in the VWF gene. The laboratory and clinical phenotype of type 2B is heterogeneous. We investigated associations between genotype and phenotype over median 16-years follow-up, in a large cohort of well-characterized patients. We included 64 genetically confirmed type 2B VWD patients from the national multicenter "Willebrand in the Netherlands" (WiN) study and retrospectively collected clinical and laboratory data from electronic patient records. We analyzed associations between genotype and thrombocytopenia, bleeding phenotype, and events leading to endothelial activation and VWF secretion, including surgery, desmopressin administration, pregnancy and delivery. Thrombocytopenia manifested in 67.2% of patients, with varying occurrences between genetic variants (p.Arg1306Trp: 75.0%, p.Arg1308Cys: 58.3%). The most important determinant of thrombocytopenia was the p.Arg1306Trp VWF variant (OR 25.1). Platelet counts strongly varied over time and were continuously <150*10 This study reveals a strong association between VWF variant p.Arg1306Trp and thrombocytopenia in type 2B patients.

Sections du résumé

BACKGROUND/OBJECTIVES OBJECTIVE
Type 2B Von Willebrand disease (VWD) is a bleeding disorder caused by gain-of-function variants in the VWF gene. The laboratory and clinical phenotype of type 2B is heterogeneous. We investigated associations between genotype and phenotype over median 16-years follow-up, in a large cohort of well-characterized patients.
PATIENTS/METHODS METHODS
We included 64 genetically confirmed type 2B VWD patients from the national multicenter "Willebrand in the Netherlands" (WiN) study and retrospectively collected clinical and laboratory data from electronic patient records. We analyzed associations between genotype and thrombocytopenia, bleeding phenotype, and events leading to endothelial activation and VWF secretion, including surgery, desmopressin administration, pregnancy and delivery.
RESULTS RESULTS
Thrombocytopenia manifested in 67.2% of patients, with varying occurrences between genetic variants (p.Arg1306Trp: 75.0%, p.Arg1308Cys: 58.3%). The most important determinant of thrombocytopenia was the p.Arg1306Trp VWF variant (OR 25.1). Platelet counts strongly varied over time and were continuously <150*10
CONCLUSIONS CONCLUSIONS
This study reveals a strong association between VWF variant p.Arg1306Trp and thrombocytopenia in type 2B patients.

Identifiants

DOI: 10.1016/j.jtha.2024.08.028 PMID: 39343102
pubmed: 39343102
pii: S1538-7836(24)00555-5
doi: 10.1016/j.jtha.2024.08.028
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

Auteurs

Calvin B van Kwawegen (CB)

Dept. of Hematology, Erasmus MC, University Medical Center Rotterdam, The Netherlands.

Ferdows Atiq (F)

Dept. of Hematology, Erasmus MC, University Medical Center Rotterdam, The Netherlands.

Dara Endenburg (D)

Dept. of Hematology, Erasmus MC, University Medical Center Rotterdam, The Netherlands.

Karin Fijnvandraat (K)

Amsterdam UMC, University of Amsterdam, Emma Children's Hospital, Pediatric Hematology, Amsterdam, The Netherlands; Dept. of Plasma Proteins, Sanquin Research, Amsterdam, The Netherlands.

Karin P M van Galen (KPM)

Van Creveldkliniek, University Medical Center Utrecht, University Utrecht, Utrecht, The Netherlands.

Marjon H Cnossen (MH)

Dept. of Pediatric Hematology and Oncology, Erasmus MC Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam.

Saskia E M Schols (SEM)

Dept. of Hematology, Radboud university medical center, and Hemophilia Treatment Center Nijmegen-Eindhoven-Maastricht, Nijmegen, The Netherlands.

Marieke J H A Kruip (MJHA)

Dept. of Hematology, Erasmus MC, University Medical Center Rotterdam, The Netherlands.

Waander L van Heerde (WL)

Dept. of Hematology, Radboud university medical center, and Hemophilia Treatment Center Nijmegen-Eindhoven-Maastricht, Nijmegen, The Netherlands; Enzyre, Nijmegen, the Netherlands.

Joke de Meris (J)

Netherlands Hemophilia Society, Leiden, The Netherlands.

Johanna G van der Bom (JG)

Dept. of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands; Jon J van Rood Center for Clinical Transfusion Medicine, Sanquin Research, Leiden, The Netherlands.

Jeroen Eikenboom (J)

Dept. of Internal Medicine, Division of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands; Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands.

Karina Meijer (K)

Dept. of Hematology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Frank W G Leebeek (FWG)

Dept. of Hematology, Erasmus MC, University Medical Center Rotterdam, The Netherlands. Electronic address: F.leebeek@erasmusmc.nl.

Classifications MeSH