Assessment of a diagnostic algorithm to classify von Willebrand disease

Karin Littmann1,*, Maria Berndtsson1, Eva-Marie Norberg1, Jovan Antovic1

1Clinical Chemistry, Karolinska University Laboratory, Stockholm, Sweden

Introduction:  Von Willebrand disease (vWD) is the most common inherited bleeding disorder and is classified into three different types .The diagnose  is based on laboratory results, family- and bleeding history.  
At Karolinska University Laboratory in Stockholm, Sweden we perform analysis of vWF-activity (vWF:GP1bA), vWF-antigen (vWF:Ag), vWF-collagen binding (vWF:CB) and ristocetin induced platelet aggregation test (RIPA). Multimer analysis of vWF is performed at Medilys Laborgesellschaft, Hamburg, Germany.
We use an algorithm including vWF:Ag, vWF:GPIbA, vWF:GPIbA/Ag-ratio and vWF:CB/Ag-ratio as a tool for classification of vWD.

Objectives:  Assess the usefulness of this algorithm to classify the different types of vWD.

Methods: We compared the results from the algorithm with a multimer analysis in 54 samples from patients with vWD referred to our laboratory in 2010-2013. The multimer analysis was considered as golden standard and when the algorithm suggested the same type (and subtype) of vWD it was considered correct.  

Results: The 54 samples had following diagnoses according to the multimer analysis: Type 1 70%, Type 2A 15%, Type 2A or 2B 4%, Type 2 M 6%, Type 2N and Type 1 2%, acquired vWD 4%. The total agreement between the algorithm and the multimer analysis was 44%. Samples diagnosed with vWD type 1 had the best agreement, 88%.

Type according to the algorithm


Agreement with multimer analysis, %




Type 2 A or 2 B



Type 2 M



Type 2, unspecified






Conclusion: The diagnostic algorithm shows poor compliance with the multimer analysis. Abnormal vWF:GPIbA should always be completed with vWF:Ag when vWD is suspected.  Before further investigations with vWF:CB the patient’s medical history should be considered. It seems that a multimer analysis has to be performed regardless what the algorithm suggests. RIPA, factor VIII-binding capacity of vWF or a genetic analysis may give more additional information than the algorithm alone.

Keywords: Blood, Laboratory organization, Method