Advances in diagnosis of von Willebrand disease

ABSTRACT

Introduction: The diagnosis of von Willebrand disease (VWD) may be difficult and is based on the assessment of bleeding history and several diagnostic assays, which evaluate the pleiotropic function of von Willebrand factor (VWF). Laboratory diagnosis requires a series of assays to determine VWF concentration and function, and factor VIII activity, but no single test is available to explore all VWF activities to confirm or exclude diagnosis.

Areas covered: This review describes the advances in diagnosing VWD, starting from how to define and quantify the bleeding history to the new assays exploring VWF activities.

Expert opinion: VWD is the most common inherited bleeding disorder, is highly heterogeneous, and its appropriate diagnosis may represent a complex laboratory task, especially for type 2 variants. Until recently, the ristocetin cofactor activity assay has represented the standard method for measuring VWF activity, as its ability to bind to platelets in presence of ristocetin, but it has low sensitivity and high variability of results. Novel assays are increasingly used, are often automated and correlate excellently with the standard assay but sometimes discrepant results may lead to a different classification of VWD. The VWF-collagen binding assay is a useful complementary assay to better categorize type 2 variants.

KEYWORDS:

• Vonwillebrand factor
• von Willebrand disease
• bleeding
• quantitative defect
• qualitative defect
• VWF:Ag
• VWF:RCo
• VWF:CB

Article highlights

• The diagnosis of VWD requires the demonstration of a bleeding history and a combination of different diagnostic assays, which evaluate the pleiotropic functions of VWF.

• ISTH-BAT is helpful to evaluate the history and severity of bleeding symptoms.

• Patients with borderline low VWF levels and mild bleeding symptoms remain challenging.

• The quantitative VWF defects are relatively easy to diagnose as type 1 or type 3 VWD.

• New assays of VWF-platelet binding may improve accuracy in diagnosis of subtypes of type 2 VWD.

• Collagen binding represents an additional useful test for VWF features not measured by current assays.

This box summarizes key points contained in the article.

Declaration of interest

G Castaman is on the advisory board and a speaker for Kedrion, CSL Behring, Shire and Werfen; S Linari is on the advisory board and a speaker for CSL Behring. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.