Laboratory Testing for von Willebrand Disease: Toward a Mechanism-Based Classification

Abstract

The heterogeneity of von Willebrand disease reflects the varied roles of von Willebrand factor in coagulation. Significant challenges remain in the detection, classification, and determination of bleeding risk in disorders related to von Willebrand factor. A clearer understanding of the specific disease mechanisms is essential to the development of improved methods for prognosis and management in this and other conditions with abnormalities of the von Willebrand factor system.

Evaluation of a new commercial method for von Willebrand factor multimeric analysis

“…1 There can be considerable genetic and phenotypic heterogeneity amongst patients with VWD, including heterogeneity in multimeric patterns, which is well known to present challenges for accurate disease subtyping. 1,6,7,[10][11][12][13] While our study demonstrates discordances between the 2 multimer testing methods in a minority of specimens (5 of 24), it should be emphasized that this is not necessarily due to differences between the methods themselves, but could also be due to the somewhat subjective nature of interpretation of this qualitative test designed primarily to determine presence or absence of the largest multimers. Previous publications have proposed arbitrary definitions to describe multimer distribution.…”

“…None of the slight differences were considered clinically significant since multimeric pattern alone does not determine VWD diagnosis, subtype, or appropriate treatment, but requires close correlation with clinical information and the results of other testing . There can be considerable genetic and phenotypic heterogeneity amongst patients with VWD, including heterogeneity in multimeric patterns, which is well known to present challenges for accurate disease subtyping …”

Clinical Measurement of von Willebrand Factor by Fluorescence Correlation Spectroscopy

“…It is normally present in plasma as a distribution of multimers containing anywhere from 2 to 40 or more vWF monomers. Abnormalities in vWF activity, most often related to abnormal concentration or multimer distribution, are the incident cause of the group of coagulopathies known as von Willebrand disease (vWD) (1, 2). As a group, vWD is considered to be the most common inherited coagulation disorder.…”

Rituximab effectiveness in a patient with juvenile systemic lupus erythematosus complicated with acquired Von Willebrand syndrome

“…11 Inhibitory antibodies in AvWS can sometimes be detected using neutralization assays of vWF:RCo, vWF:Ag, vWF:CB, or ristocetin-induced platelet aggregation; however, these assays are technically demanding, their sensitivity and specificity are unproven and will fail to detect non-neutralizing antibodies. 9,12 The non-neutralizing autoantibodies accelerate vWF clearance from the circulation without inhibiting the measurable functions of vWF. Non-neutralizing vWF-binding antibodies can be detected by ELISA.…”