title: Frequency of platelet type versus type 2B von Willebrand disease. An international registry-based study.
abstract: Less than 50 patients are reported with platelet type von Willebrand disease (PT-VWD) worldwide. Several reports have discussed the diagnostic challenge of this disease versus the closely similar disorder type 2B VWD. However, no systematic study has evaluated this dilemma globally. Over three years, a total of 110 samples/data from eight countries were analysed. A molecular approach was utilised, analysing exon 28 of the von Willebrand factor (VWF) gene, and in mutation negative cases the platelet GP1BA gene. Our results show that 48 cases initially diagnosed as putative type 2B/PT-VWD carried exon 28 mutations consistent with type 2B VWD, 17 carried GP1BA mutations consistent with a PT-VWD diagnosis, three had other VWD types (2A and 2M) and five expressed three non-previously published exon 28 mutations. Excluding 10 unaffected family members and one acquired VWD, 26 cases did not have mutations in either genes. Based on our study, the percentage of type 2B VWD diagnosis is 44% while the percentage of misdiagnosis of PT-VWD is 15%. This is the first large international study to investigate the occurrence of PT-VWD and type 2B VWD worldwide and to evaluate DNA analysis as a diagnostic tool for a large cohort of patients. The study highlights the diagnostic limitations due to unavailability/poor application of RIPA and related tests in some centres and proposes genetic analysis as a suitable tool for the discrimination of the two disorders worldwide. Cases that are negative for both VWF and GP1BA gene mutations require further evaluation for alternative diagnoses.
authors.affiliation: Laurentian University, St Lawrence College Collaborative Program, Kingston, Ontario, Canada.
authors.forename: Alexander
authors.initials: A
authors.lastname: Hamilton
authors.forename: Margareth
authors.initials: M
authors.lastname: Ozelo
authors.forename: Jayne
authors.initials: J
authors.lastname: Leggo
authors.forename: Colleen
authors.initials: C
authors.lastname: Notley
authors.forename: Hannah
authors.initials: H
authors.lastname: Brown
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Frontroth
authors.forename: Anne
authors.initials: A
authors.lastname: Angelillo-Scherrer
authors.forename: Fariba
authors.initials: F
authors.lastname: Baghaei
authors.forename: Said M
authors.initials: SM
authors.lastname: Enayat
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Favaloro
authors.forename: David
authors.initials: D
authors.lastname: Lillicrap
authors.forename: Maha
authors.initials: M
authors.lastname: Othman
mesh_terms: D001791:Blood Platelet Disorders / Q000235:genetics; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D005091:Exons; D005260:Female; D006487:Hemostasis; D006801:Humans; D007391:International Cooperation; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D009154:Mutation; D010976:Platelet Count; D019038:Platelet Glycoprotein GPIb-IX Complex; D012042:Registries; D056728:von Willebrand Disease, Type 2 / Q000097:blood* / Q000453:epidemiology; D014841:von Willebrand Factor / Q000096:biosynthesis*
chemical_list: D008562:Membrane Glycoproteins; D019038:Platelet Glycoprotein GPIb-IX Complex; C094990:adhesion receptor; D014841:von Willebrand Factor; D004247:DNA