Updated overview on von Willebrand disease: focus on the interest of genotyping

Abstract

Introduction: Von Willebrand disease (VWD) is the most common inherited bleeding disorder, characterized by a quantitative or qualitative defect of von Willebrand factor (VWF), a multimeric glycoprotein crucial for primary hemostasis and coagulation. VWD pathophysiology is heterogeneous as it includes several types and subtypes which therapeutic management is different. The mainstays of VWD treatment are desmopressin and replacement therapy based on both plasma-derived concentrates and a recently developed recombinant VWF. VWD definitive diagnosis is achieved by a battery of phenotypic biologic assays and genotyping is currently performed mostly for research.Areas covered: This narrative review will firstly present a general overview on VWD epidemiology, pathophysiology, classification, clinics, phenotypic biologic diagnosis, and treatment. Secondly, a focus on VWD genotyping will be presented with specific emphasis on the evolution of its technical aspects, its applications for research dedicated to a better understanding of VWD pathophysiology and epidemiology and its interest in both a faster diagnosis and an optimal treatment of VWD.Expert opinion: Based on analysis of the literature, it can be concluded that the fast evolution of genetic techniques together with the development of innovating treatments may significantly change diagnostic flow charts for VWD and their use for specific and personalized treatment.

Keywords: ADAMTS13; NGS sequencing; Sanger sequencing; Von Willebrand disease; bleeding; genotype; multimers; phenotype; plasma-derived concentrates; recombinant von Willebrand factor.