Diagnosis or Exclusion of von Willebrand Disease Using Laboratory Testing

Abstract

von Willebrand disease (VWD) is a common bleeding disorder diagnosed based on clinical features and following laboratory testing. VWD is due to deficiencies or defects in the plasma protein von Willebrand factor (VWF), a large adhesive protein with multiple activities. Laboratory testing therefore centers on assessment of VWF protein level using VWF antigen (VWF:Ag), as well as assays that measure VWF activity, most notably platelet glycoprotein (GP) Ib and collagen binding (VWF:CB) activities. Decreases in VWF:Ag and VWF activities, as well as the pattern of such changes, help define VWD and its type. Classically, the most often used assay for measuring GPIb binding activity was the ristocetin cofactor assay (VWF:RCo), which historically measured agglutination of fixed human platelets by VWF in the presence of ristocetin. This assay is now often replaced or supplemented with other assays based on binding of VWF to recombinant GPIb, generally without the use of platelets, and with or without ristocetin. This chapter briefly reviews laboratory tests for VWD, as well as recommended approaches to use of such assays to help diagnose or exclude VWD in patients showing clinical features.

Postanalytical considerations that may improve the diagnosis or exclusion of haemophilia and von Willebrand disease

“…As mentioned, we recently published on preanalytical issues, and do not intend to replicate this discussion here, other than providing, where necessary, some contextual background. Recent analytical aspects of testing for VWD and haemophilia are also well represented in the literature, including our own work . Nonetheless, the large bulk of literature around analytical issues, and indeed the wide and diverse availability of testing for VWF, may sometimes confuse rather than enlighten workers in the field.…”

“…For VWD, the sheer number of tests available, their variable methodology, variable sensitivity to low VWF levels or high molecular weight VWF, as well as the different composite test panels in use, often compromise VWD diagnosis/exclusion, as otherwise reported . In brief, VWF expresses several activities, including: (a) platelet binding (mostly via glycoprotein [Gp] Ib), (b) subendothelial matrix binding (mostly via collagen), (c) FVIII binding.…”

“…Although von Willebrand disease (VWD) and haemophilia represent together the most common inherited and acquired bleeding disorders, many laboratories and clinicians may be challenged to achieve an accurate diagnosis or exclusion for their patients . VWD essentially arises due to deficiency and/or defect(s) of von Willebrand factor (VWF), which in turn is an adhesive plasma protein essential for effective primary haemostasis .…”

“…In contrast, VWF expresses a multitude of functional properties, which helps explain the heterogeneity of clinical symptoms and bleeding risk in affected VWD patients, as well as diagnostic challenges. A comprehensive panel of tests is therefore needed to exclude or diagnose VWD, and then assign a specific VWD type . At least in theory, then, testing for associated factor defects/deficiencies is more straight forward than for VWF/VWD.…”

“…A comprehensive panel of tests is therefore needed to exclude or diagnose VWD, and then assign a specific VWD type. [1][2][3] At least in theory, then, testing for associated factor defects/deficiencies is more straight forward than for VWF/VWD. Failure to achieve the correct diagnosis or exclusion of VWD or haemophilia might be due to analytical issues.…”