Laboratory tests used to help diagnose von Willebrand disease: an update

Preclinical evaluation of a semi‐automated and rapid commercial electrophoresis assay for von Willebrand factor multimers

“…von Willebrand factor (VWF) is a large multimeric adhesive sialoglycoprotein that mediates platelet adhesion to sub‐endothelium structures and acts as a factor VIII (FVIII) carrier molecule, thus stabilizing the procoagulant activity of FVIII in the circulation . The protein is synthesized by endothelial cells and megakaryocytes as a polypeptide and is composed of identical monomers that assemble into a series of multimers. The multimer organization is critical for the function of VWF .…”

“…The multimer organization is critical for the function of VWF . Multimers may range in size from 500 kDa to ˃20 000 kDa and are usually classified into categories according to the number of multimers (dimers) and size: low‐molecular‐weight (LMW, 1‐5 dimers, 500‐2500 kDa), intermediate‐molecular‐weight (IMW, 6‐10 dimers, 3000‐5000 kDa), high‐molecular‐weight (large) (HMW, 11‐20 dimers, 5500‐10 000 kDa), and ultra‐high‐molecular‐weight (ultra‐large) (UHMW, >20 dimers, up to 20 000 kDa) forms . UHMW multimers do not typically circulate in blood because of rapid proteolysis by the disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (known as ADAMTS13) that cleaves UHMW forms into smaller multimers soon after secretion…”

“…von Willebrand disease (VWD) is the most common congenital bleeding disorder, with a worldwide prevalence of 1% . The current classification of VWD variants by the International Society on Thrombosis and Haemostasis (ISTH) recognizes six different types, reviewed with updates elsewhere .…”

“…von Willebrand disease (VWD) is the most common congenital bleeding disorder, with a worldwide prevalence of 1% . The current classification of VWD variants by the International Society on Thrombosis and Haemostasis (ISTH) recognizes six different types, reviewed with updates elsewhere . The diagnosis of VWD is aided by good correlation between the clinical picture and traditional (screening) assays, such as FVIII, VWF antigen (VWF:Ag), VWF activity (VWF:RCo or alternatively VWF:Ac), and, in some cases, the collagen binding capacity of VWF (VWF:CB) .…”

“…The diagnosis of VWD is aided by good correlation between the clinical picture and traditional (screening) assays, such as FVIII, VWF antigen (VWF:Ag), VWF activity (VWF:RCo or alternatively VWF:Ac), and, in some cases, the collagen binding capacity of VWF (VWF:CB) . Classical screening assays are highly heterogeneous in terms of methodology and diagnostic efficacy; thus, they may lead to over‐, under‐ or misdiagnosis and inadequate or inappropriate treatment of affected patients . Therefore, additional confirmatory VWD tests, such as VWF multimers, are needed to distinguish type 2A and 2B VWD from type 2M (or type 1) VWD and diagnose acquired VWD.…”