Diagnostic challenges in patients with bleeding phenotype and von Willebrand exon 28 polymorphism p.D1472H

Francis, Jessica; Hui, Shiu‐Ki Rocky; Mahoney, Donald H.; Dietrich, Jennifer E.; Friedman, Kenneth D.; Soundar, Esther; Srivaths, Lakshmi

doi:10.1111/hae.12384

Cited by 5 publications

(1 citation statement)

References 12 publications

(14 reference statements)

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“…This report demonstrates that the reliance on VWF:RCo alone for diagnostic purposes can be insufficient, especially in those with the p.D1472H variant. Francis et al 9 showed similar results from a single institution study in which their retrospective analysis uncovered six patients diagnosed with type 1 VWD who had normal VWF:Ag levels and borderline low VWF:RCo, which could be explained by the presence of p.D1472H. Our data expand on this study and highlight the value of repeat testing along with using the VWF:GPIbM assay to avoid the potential pitfalls of the VWF:RCo assay.…”

Section: Ta B L E 1 Demographics Of Study Populationsupporting

confidence: 85%

Ristocetin dependent cofactor activity in von Willebrand disease diagnosis: Limitations of relying on a single measure

Christopherson

Haberichter

Flood

et al. 2022

Research and Practice in Thrombosis and Haemostasis

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Background: Von Willebrand disease (VWD) is a common inherited bleeding disorder, however the diagnosis can be complicated by a subjective bleeding history and issues with some current von Willebrand factor (VWF) laboratory assays. Objectives: In the Zimmerman Program, we sought to determine how often a type 1 diagnosis was based on a single low VWF ristocetin cofactor (VWF:RCo) level resulting from the common genetic variant p.D1472H or an isolated assay issue, if that low value was corroborated by the VWF glycoprotein-IbM (VWF:GPIbM) assay, and if retesting confirmed original levels. Methods: New patients being evaluated for bleeding were consented. Analysis included VWF sequencing, bleeding scores, and comparisons of local VWF antigen (VWF:Ag) and VWF:RCo to central VWF:Ag and VWF:GPIbM. Results: A total of 18% of VWD subjects had a low local VWF:RCo, but normal VWF:Ag and normal central testing including VWF:GPIbM. Seventy percent of the low VWF:RCo cohort had no pathogenic VWF variants; however, 33% carried p.D1472H. Low VWF:RCo subjects with follow-up local testing within 2 years showed those with p.D1472H continued to have low VWF:RCo and VWF:RCo/VWF:Ag ratio with normal VWF:GPIbM. Subjects without p.D1472H had an increase mean VWF:RCo, resulting in 59% with normal levels on repeat testing. Conclusions:The diagnosis of VWD based on a single low VWF:RCo but normal VWF:Ag, was often attributed to p.D1472H or variability in VWF:RCo that was eliminated with VWF:GPIbM. Our study suggests that using VWF:RCo alone for diagnostic purposes may be insufficient while repeat VWF:RCo or VWF:GPIbM testing can be valuable in establishing a VWD diagnosis.

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Section: Ta B L E 1 Demographics Of Study Populationsupporting

confidence: 85%