title: von Willebrand disease R1374C: type 2A or 2M? A challenge to the revised classification. High frequency in the northwest of Spain (Galicia).
abstract: Patients initially diagnosed with type 1 von Willebrand disease (VWD) have been reclassified as type 2 after a more exhaustive analysis in several studies. Our study's objectives were (1) to reanalyze patients that were previously diagnosed as type 1 to achieve a more accurate diagnosis and (2) to compare the von Willebrand factor (VWF) ristocetin cofactor assay (VWF:RCo) and the VWF collagen binding assay (VWF:CB) in order to evaluate the possibility of replacing the former assay with the latter in the diagnosis of VWD. Twenty-one patients from two large unrelated families and 104 normal controls were studied. VWF:Ag, VWF:RCo, FVIII coagulant activity (FVIII:C), bleeding time (BT), PFA(100), and multimeric analysis of VWF were tested. Genetic analysis by sequencing exon 28 on the VWF gene was also carried out. Patients presented lower levels of VWF:Ag and VWF:RCo, a dissociation between VWF:RCo/VWF:Ag, and the presence of all sizes of multimers in plasma VWF. The results for VWF:CB varied depending on the type of collagen used. The genetic analysis showed that the mutation R1374C is responsible for type 2M VWD. A high frequency of the R1374C mutation is observed in northwestern Spain (Galicia). Some types of 2M VWD are misdiagnosed as type 1 VWD. The VWF:CB (with type I collagen) assay was unable to discriminate defective platelet binding of the R1374C VWF. This confirms that VWF:CB cannot substitute for VWF:RCo, and both should be tested when diagnosing VWD.
authors.affiliation: Servicio de Hematología y Hemoterapia, Complexo Hospitalario Universitario Juan Canalejo, A Coruña, Department of Medicine, School of Medicine, University of Santiago de Compostela, Spain.
authors.forename: Norma
authors.initials: N
authors.lastname: Penas
authors.forename: Almudena
authors.initials: A
authors.lastname: Pérez-Rodríguez
authors.forename: Jorge Horacio
authors.initials: JH
authors.lastname: Torea
authors.forename: Esther
authors.initials: E
authors.lastname: Lourés
authors.forename: María Soledad
authors.initials: MS
authors.lastname: Noya
authors.forename: María Fernanda
authors.initials: MF
authors.lastname: López-Fernández
authors.forename: Javier
authors.initials: J
authors.lastname: Batlle
mesh_terms: D001780:Blood Coagulation Tests; D016022:Case-Control Studies; D002965:Classification; D003094:Collagen / Q000494:pharmacology; D004252:DNA Mutational Analysis; D003951:Diagnostic Errors; D019281:Dimerization; D005169:Factor VIII / Q000032:analysis; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D017720:Molecular Epidemiology; D020125:Mutation, Missense; D010375:Pedigree; D010979:Platelet Function Tests; D013030:Spain / Q000453:epidemiology; D014842:von Willebrand Diseases / Q000145:classification* / Q000175:diagnosis / Q000235:genetics*; D014841:von Willebrand Factor / Q000032:analysis
chemical_list: D014841:von Willebrand Factor; D005169:Factor VIII; D003094:Collagen