title: Diagnostic challenges in patients with bleeding phenotype and von Willebrand exon 28 polymorphism p.D1472H.
abstract: Exon 28 polymorphism p.D1472H is associated with significantly lower von Willebrand Ristocetin cofactor activity (VWF:RCoF) to von Willebrand antigen (VWF:Ag) ratio compared to normal, but has been reported as not conferring haemorrhagic risk. The impact of this polymorphism while assessing symptomatic patients for von Willebrand disease (VWD) has not been previously analysed. We retrospectively reviewed charts of children with clinically significant bleeding and abnormal VW panel who underwent VW exon 28 analysis. Twenty-three of 63 patients studied had p.D1472H. Of these 23 patients, 6 with borderline low VWF:RCo were given provisional diagnosis of VWD type 1 by treating physicians, which could be alternatively explained as due to the effect of p.D1472H. None of the patients with low VWF:RCo, decreased VWF:RCo/VWF:Ag ratio and p.D1472H had VWD type 2M mutations identified. This study illustrates the challenge in diagnosing VWD using ristocetin-based VW assay in symptomatic patients with p.D1472H.
authors.affiliation: Division of Pediatric and Adolescent Gynecology, Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX, USA; Department of Pathology, Baylor College of Medicine, Houston, TX, USA; Baylor College of Medicine, Houston, TX, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Francis
authors.forename: S K
authors.initials: SK
authors.lastname: Hui
authors.forename: D
authors.initials: D
authors.lastname: Mahoney
authors.forename: J E
authors.initials: JE
authors.lastname: Dietrich
authors.forename: K D
authors.initials: KD
authors.lastname: Friedman
authors.forename: E
authors.initials: E
authors.lastname: Soundar
authors.forename: L V
authors.initials: LV
authors.lastname: Srivaths
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005091:Exons; D006470:Hemorrhage / Q000235:genetics*; D006801:Humans; D007223:Infant; D010641:Phenotype; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D014842:von Willebrand Diseases / Q000175:diagnosis* / Q000235:genetics*; D014841:von Willebrand Factor / Q000235:genetics*
chemical_list: D014841:von Willebrand Factor
keywords: exon 28; p.D1472H; von Willebrand