Abstract
The multimeric analysis (MA) of plasma von Willebrand factor (VWF) evaluates structural integrity and helps in the diagnosis of von Willebrand disease (VWD). This assay is a matter of controversy, being considered by some investigators cumbersome and only slightly informative. The centralised study ‘Molecular and Clinical Profile of von Willebrand Disease in Spain (PCM-EVW-ES)’ has been carried out by including the phenotypic assessment and the genetic analysis by next generation sequencing (NGS) of the VWF gene (VWF). The aim of the present study was to evaluate the role of MA to the diagnosis of these patients and their potential discrepancies. Two hundred and seventy out of 480 patients centrally diagnosed with VWD had normal multimers, 168 had abnormal multimers and 42 a total absence of multimers. VWF MA was of great significance in the diagnosis of 83 patients (17.3%), it was also of help in the diagnosis achieved in 365 additional patients (76%) and was not informative in 32 cases (6.7%). With regard to discrepancies, 110 out of 480 (23%) patients centrally diagnosed with VWD presented some kind of discordance between VWF:RCo/VWF:Ag and/or VWF:CB/VWF:Ag ratios, multimeric study and/or genetic results. The VWF MA was key in the presence of novel mutations as well as in cases with phenotypic discrepancies. A comparison between the contribution of MA and VWF:CB showed a clearly higher contribution of the former in the diagnostic process. These data seem to reinforce the relevance of the VWF MA in VWD diagnosis, despite all its limitations.
Highlights
Introduction von Willebrand disease (VWD) is the most frequent inherited bleeding disorder caused by defects in the amount, structure or function of von Willebrand factor (VWF), which has an important role in primary haemostasis, as well as to bind and stabilize coagulation factor VIII (FVIII) [1,2]
The screening tests used to classify VWD are the VWF antigen (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo), factor VIII activity (FVIII:C), and VWF collagen binding (VWF: CB), whereas the confirmatory tests include ristocetin-induced platelet agglutination (RIPA), VWF capacity to bind exogenous FVIII (VWF:FVIIIB), VWF propeptide (VWFpp), and multimeric analysis (MA), which are especially useful to differentiate between the different types of VWD
Some laboratories have von Willebrand factor multimeric analysis in von Willebrand disease diagnosis dispensed with MA technique, claiming that VWD classification can be reliably achieved with a combination of FVIII:C, some standard VWF assays (VWF:Ag, VWV:RCo and VWF:CB), as well as genotype analysis in some cases [14,15]
Summary
The latest official classification of VWD refers to the VWF multimeric profile [12], considering that the MA is in the phenotypic classification an integral part of the diagnostic process. The diagnosis and classification of VWD is based on phenotype and not on genotype because it does not even require the presence of a genetic mutation in the VWF gene (VWF). Some laboratories have von Willebrand factor multimeric analysis in von Willebrand disease diagnosis dispensed with MA technique, claiming that VWD classification can be reliably achieved with a combination of FVIII:C, some standard VWF assays (VWF:Ag, VWV:RCo and VWF:CB), as well as genotype analysis in some cases [14,15]. From a clinician’s perspective, some opinion considers that what really matters in VWD diagnosis is whether a patient responds to desmopressin (DDAVP), and formal VWD subclassification in a laboratory is not necessary
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
