A new case of platelet‐type von Willebrand disease supports the recent findings of gain‐of‐function <i>GP1BA</i> variants outside the C‐terminal disulphide loop enhances affinity for von Willebrand factor
Catarina Monteiro, Ana Gonçalves, Mónica Pereira, Catarina Lau, Sara Moráis, Rosário Santos
Abstract
Platelet-type von Willebrand disease (PT-VWD) is a rare autosomal dominant bleeding disorder characterized by an increased ristocetin-induced platelet aggregation (RIPA) and enhanced affinity of platelet glycoprotein Ibα (GPIbα) to von Willebrand factor (VWF). To date, only seven variants have been described with this gain-of-function effect, most of them located in the C-terminal disulphide loop of the VWF-binding domain of GPIbα. We herein describe a patient with moderate bleeding symptoms, mild thrombocytopenia and increased RIPA. By direct sequencing of GP1BA, a novel leucine-rich repeat heterozygous variant was identified (c.580C>T; predictably p.Leu194Phe), strongly suggestive as being the underlying cause for the PT-VWD phenotype of our patient.