title: Spontaneous hemarthrosis in combined Glanzmann thrombasthenia and type 2N von Willebrand disease.
abstract: Glanzmann thrombasthenia is a rare autosomal recessive inherited bleeding disorder characterized by the lack of platelet aggregation, caused by deficiencies and/or abnormalities of platelet GPIIb-IIIa receptor. We report a case of Glanzmann thrombasthenia combined with type 2N von Willebrand disease (VWD), a variant characterized by an impaired capacity of FVIII to bind von Willebrand factor (VWF), which results in an autosomally transmitted reduction in circulating FVIII levels. Glanzmann thrombasthenia stems from compound T1214C and G1234A mutations in the ITGA2B gene; the type 2N VWD is due to a heterozygous G2561A mutation in the VWF gene (R854Q). The haemostatic phenotype of a 48-year-old female patient was unusually characterized by a severe chronic arthropathy with loss of cartilage and the presence of subchondrial cysts involving both ankles. The arthropathy was quantified with the compatible MRI scoring system (currently used to assess arthropathy in haemophilia), reaching almost the highest score. These haemorrhagic complications are very rare in Glanzmann thrombasthenia and resemble those seen in severe haemophilia; for such, a reason we decided to explore the patient's FVIII and VWF parameters. Our findings suggest that the type 2N R854Q mutation, which is normally asymptomatic at the heterozygous level, may be expressed in the presence of a combined impairment of primary haemostasis.
authors.affiliation: aDepartment of Cardiologic, Thoracic and Vascular Sciences, University of Padua Medical School, Padua bDepartment of Internal Medicine, University of Perugia, Perugia cDepartment of Medicine, University of Padua Medical School, Padua, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Pontara
authors.forename: Paolo
authors.initials: P
authors.lastname: Gresele
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Cattini
authors.forename: Viviana
authors.initials: V
authors.lastname: Daidone
authors.forename: Giovanni
authors.initials: G
authors.lastname: Barbon
authors.forename: Antonio
authors.initials: A
authors.lastname: Girolami
authors.forename: Ezio
authors.initials: E
authors.lastname: Zanon
authors.forename: Alessandra
authors.initials: A
authors.lastname: Casonato
mesh_terms: D005260:Female; D006395:Hemarthrosis / Q000097:blood*; D006801:Humans; D008875:Middle Aged; D013915:Thrombasthenia / Q000097:blood*; D056728:von Willebrand Disease, Type 2 / Q000097:blood*