Diagnosis and management of von Willebrand disease in Australia

Abstract

Von Willebrand disease (VWD) is the most common inherited bleeding disorder and arises from deficiencies and/or defects in the plasma protein Von Willebrand factor (VWF). VWD is classified into six different types, with type 1 identifying a (partial) quantitative deficiency of VWF, type 3 defining a (virtual) total deficiency of VWF, and type 2 identifying four separate types (2A, 2B, 2M, and 2N) characterized by qualitative defects. The classification is based on phenotypic assays including factor VIII coagulant, VWF antigen, and VWF activity, primarily by ristocetin cofactor and collagen binding, as supplemented by additional testing. In Australia, >30 pathology-based laboratories perform VWD testing, and tests and test panels reflect a wide variety of practice. In our own referral laboratory, diagnosis is a staged process reflecting a combination of clinical and laboratory findings with a large panel of tests. We also use data from desmopressin trials to assist in VWD type assignment. The current report presents an overview of the VWD diagnostic process as applied within Australia, includes summary data from the Australian Bleeding Disorders Registry, and provides specific details of the diagnostic and management practice undertaken in our reference laboratory, which also maintains a local bleeding disorders database. This database currently contains 4070 entries, including 1832 suspected or confirmed cases of VWD. Excluding 311 as yet unclassified cases, 1254 cases (82.4%) would define (potential) quantitative deficiencies of VWF ("low VWF" or type 1 VWD), 241 (15.8%) qualitative defects (type 2 VWD), and 23 (1.5%) type 3 VWD. Most of the quantitative defects reflect only mild loss of VWF, and <15% of total cases would be identified to have VWF levels <35 U/dL. Most cases of type 2 remain unclassified (34.9%) because available data are limited. Type 2A and 2M VWD represent the most common qualitative defects, representing 22.8% and 22.2% of defined type 2 VWD cases. Type 2B and 2N reflect 8.3% and 12.9%, respectively, of type 2 VWD cases.