Laboratory Diagnosis of von Willebrand Disease (VWD): Geographical Perspectives

Abstract

Abstractvon Willebrand disease (VWD) is reportedly the most common inherited bleeding disorder, and can also arise as an acquired (von Willebrand) syndrome (AVWS). The hemostasis laboratory plays a key role in the diagnosis or exclusion of VWD/AVWS, which may otherwise be suspected due to the patient's clinical (bleeding) history. VWD/AVWS arise from deficiency and/or defects in the adhesive plasma protein, von Willebrand factor (VWF). VWF undertakes various roles within hemostasis, but principally acts within primary hemostasis to anchor platelets to sites of vascular damage, thereby facilitating thrombus formation to arrest bleeding. The diagnosis or exclusion of VWD/AVWS requires laboratory testing for both VWF level and activity, with the latter potentially comprising several of a potential plethora of different assays. Complete diagnosis of VWD also requires the differentiation of VWD type, with six types comprising the current classification (i.e., qualitative [types 2A, 2B, 2M, 2N VWD] vs. quantitative [types 1 and 3 VWD] deficiency/defects). Although appropriate diagnosis and type classification hold important therapeutic consequences, these remain problematic and sometimes elusive for some laboratories to achieve. This report reviews the laboratory aided diagnosis or exclusion of VWD from a geographic perspective, and focuses on the disparities of approaches and methods in different regions of the world. This is primarily done from the perspective of data available from published reports related to external quality assessment (or proficiency testing) from different geographic localities. Moreover, differences in approaches between laboratories may arise due to differential adherence of particular guidelines, as well as regulatory aspects and predominance of local manufacturers and suppliers.

Evaluating Performance of Contemporary and Historical von Willebrand Factor (VWF) Assays in the Laboratory Identification of von Willebrand Disease (VWD): The Australasian Experience

“…50 In terms of findings from other EQA providers, a separate publication in this issue of the journal will deal with this in some detail. 51…”

Laboratory Diagnostics for Thrombosis and Hemostasis Testing—Part I

“…The VWF papers are a special collection of updates on VWF testing patterns and assay performance and quality contributed by authors representing five external quality assessment (EQA) programs operating in North America, Europe, and Australasia. [8][9][10][11][12][13] For those less familiar, EQA participation is an important component of quality laboratory practice and required by regulatory agencies. EQA organizations challenge laboratories to test blinded lyophilized plasma specimens representing the normal condition or a disease process, in this case primarily von Willebrand disease (VWD).…”

“…Close attention must be paid to the preanalytical (specimen collection and handling), 1 analytical (the testing process), 2 and postanalytical (test interpretation contribution to diagnosis and treatment) 3 variables associated with coagulation testing to assure accurate reporting of assay result(s) and corresponding result interpretation(s). The manuscripts in this edition of the journal represent state of the art summaries of testing aspects for antiphospholipid antibodies (including lupus anticoagulant [LA] 4 and solid phase testing 5 ), D-dimer, 6 activated protein C (APC) resistance, 7 and von Willebrand factor (VWF), 8 9 10 11 12 13 highlighting information essential for accurate diagnosis and monitoring of common disorders that significantly impact health care systems and patient lives.…”

“…19 A final VWF article, authored by Favaloro and Pasalic, nicely summarizes the complexity of VWD and diagnostics. 13…”

“…To round out the VWF collection, Favaloro and Pasalic have summarized the complexity of the diagnostic landscape for VWD with a particular focus on the geographic differences due to a variety of factors. 13 Readers will be pleased to see detailed summaries of different VWF assays, making this manuscript a great resource for anyone looking to learn about the myriad different testing options for diagnosing VWD or monitoring VWD therapy. The heterogeneity of VWD, including the six currently recognized subtypes, is discussed with emphasis on the laboratory context and differences in assay performance, geographical approaches, etc.…”