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

Autor: Christopherson PA; Versiti Blood Research Institute Milwaukee Wisconsin USA., Haberichter SL; Versiti Blood Research Institute Milwaukee Wisconsin USA.; Division of Hematology/Oncology, Department of Pediatrics Medical College of Wisconsin Milwaukee Wisconsin USA.; Children's Research Institute, Children's Hospital of Wisconsin Milwaukee Wisconsin USA., Flood VH; Versiti Blood Research Institute Milwaukee Wisconsin USA.; Division of Hematology/Oncology, Department of Pediatrics Medical College of Wisconsin Milwaukee Wisconsin USA.; Children's Research Institute, Children's Hospital of Wisconsin Milwaukee Wisconsin USA., Sicking UO; Versiti Blood Research Institute Milwaukee Wisconsin USA., Abshire TC; Versiti Blood Research Institute Milwaukee Wisconsin USA., Montgomery RR; Versiti Blood Research Institute Milwaukee Wisconsin USA.; Division of Hematology/Oncology, Department of Pediatrics Medical College of Wisconsin Milwaukee Wisconsin USA.; Children's Research Institute, Children's Hospital of Wisconsin Milwaukee Wisconsin USA.
Jazyk: angličtina
Zdroj: Research and practice in thrombosis and haemostasis [Res Pract Thromb Haemost] 2022 Oct 05; Vol. 6 (7), pp. e12807. Date of Electronic Publication: 2022 Oct 05 (Print Publication: 2022).
DOI: 10.1002/rth2.12807
Abstrakt: 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.
(© 2022 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)
Databáze: MEDLINE
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