Journal article
Ristocetin dependent cofactor activity in von Willebrand disease diagnosis: Limitations of relying on a single measure
Research and practice in thrombosis and haemostasis, Vol.6(7), pp.e12807-n/a
10/01/2022
DOI: 10.1002/rth2.12807
PMCID: PMC9637542
PMID: 36381287
Abstract
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.
Details
- Title: Subtitle
- Ristocetin dependent cofactor activity in von Willebrand disease diagnosis: Limitations of relying on a single measure
- Creators
- Pamela A. Christopherson - Versiti Blood Center of WisconsinSandra L. Haberichter - Children's Hospital of WisconsinVeronica H. Flood - Children's Hospital of WisconsinUrsula O. Sicking - Versiti Blood Center of WisconsinThomas C. Abshire - Versiti Blood Center of WisconsinRobert R. Montgomery - Children's Hospital of WisconsinZimmerman Program Investigators
- Contributors
- S Lentz (Contributor) - University of Iowa, Hematology, Oncology, and Blood & Marrow Transplantation
- Resource Type
- Journal article
- Publication Details
- Research and practice in thrombosis and haemostasis, Vol.6(7), pp.e12807-n/a
- DOI
- 10.1002/rth2.12807
- PMID
- 36381287
- PMCID
- PMC9637542
- NLM abbreviation
- Res Pract Thromb Haemost
- ISSN
- 2475-0379
- eISSN
- 2475-0379
- Publisher
- Wiley
- Number of pages
- 5
- Grant note
- P01HL081588; P01HL144457; R01HL112614; R01HL126810; R01HL136430 / National Heart, Lung, and Blood Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI)
- Language
- English
- Date published
- 10/01/2022
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984359790602771
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