ORIGINAL ARTICLE
Laboratory variability in the diagnosis of type 2 VWD variants

https://doi.org/10.1111/jth.15129Get rights and content
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Essentials

  • Patients with von Willebrand disease were enrolled in our study.

  • Type 2 VWD diagnoses were based on original test results.

  • Repeat evaluation resulted in many patients receiving a different type 2 diagnosis.

  • Some genetic variants were particularly likely to move type 2 subcategories.

Abstract

Introduction

Type 2 von Willebrand disease (VWD) refers to patients with a qualitative defect in von Willebrand factor. Accurate diagnosis of type 2 VWD subtypes can be challenging.

Aim of the study

To compare the historical diagnosis of type 2 VWD with current laboratory testing.

Methods

Subjects were enrolled in the Zimmerman Program either because of a preexisting diagnosis of VWD (retrospective cohort) or from evaluation for bleeding symptoms or suspected VWD (prospective cohort). Original diagnosis was assigned by the local center and central diagnosis was based on central laboratory testing.

Results

Two hundred and seventeen index cases in the retrospective cohort and 35 subjects in the prospective cohort carried a local diagnosis of type 2 VWD (29% and 6% of enrolled index cases, respectively). In the retrospective cohort, the diagnosis was confirmed in 66% of cases with a preexisting diagnosis of 2A, 77% 2B, 54% 2M, and 72% 2N. In the prospective cohort, 31% were confirmed 2A, 60% 2B, 23% 2M, and 100% 2N. Several genetic variants were repeatedly implicated in subjects with changed diagnosis: p.M1304R, p.R1315C, p.R1374C, and p.R1374H.

Conclusions

Both the prospective and retrospective cohorts demonstrated consistent variation in subjects whose diagnosis changed between 2A, 2B, and 2M. The importance of accurately diagnosing type 2 VWD may be most significant in the 2B subtype given potential concerns with the use of desmopressin in type 2B VWD. Some genetic variants appear in multiple types of VWD, making specific diagnoses challenging.

Keywords

Von Willebrand factor
Von Willebrand disease
ristocetin
polymorphism
genetic
medical laboratory science

Cited by (0)

Manuscript handled by: Robert Gosselin

Final decision: Robert Gosselin, 29 September 2020

See Appendix 1 section