Diagnosis of platelet-type von Willebrand disease by flow cytometry

Abstract

Platelet-type von Willebrand disease (PT-VWD) is a rare autosomal dominant bleeding disorder which is due to a mutation in the gene encoding for platelet glycoprotein Ibα (GPIbα) resulting in enhanced affinity for von Willebrand factor (VWF). PT-VWD is often mistakenly diagnosed as type 2B VWD for the similarities between these two conditions. We characterized a new case of PT-VWD and evaluated the usefulness of a flow cytometric assay in the differential diagnosis between PT-VWD (n=1) and type 2B VWD (n=4). The flow cytometric assay was able to highlight the increased affinity of VWF for GPIbα as much as did RIPA and to differentiate the two diseases through mixing tests. Genetic analysis revealed a heterozygous point mutation in codon 239 of the GPIbα gene leading to a methionine to valine substitution (M239V). Flow cytometry represents a useful tool for the diagnosis of PT-VWD.