An External Quality Assessment Program for von Willebrand Factor Laboratory Analysis: An Overview from the European Concerted Action on Thrombosis and Disabilities Foundation

Abstract

The laboratory diagnosis of von Willebrand disease (vWD) is complex and requires a panel of different laboratory tests. Because of this complexity, a proper quality control process is necessary. Since 2003, the European Concerted Action on Thrombosis and Disabilities Foundation has provided an external quality control program for several laboratory tests included in the diagnosis of vWD. Currently, ~180 different laboratories participate in this program, of which the vast majority perform both von Willebrand factor (vWF):antigen (Ag) and activity tests. The lowest between-laboratory variation was observed for the vWF antigen assay (10 to 24%), with a better performance for the latex immunoassay (8 to 24%) than the enzyme immunoassay (13 to 25%). Both the ristocetin cofactor activity assay (RCo) and the collagen-binding assay showed a higher between-laboratory variation (20 to 40% and 17 to 29%, respectively). We have observed that the within-laboratory repeatability for normal samples ranged from 0 to 40% for the antigen assay and from 0 to 86% for the ristocetin cofactor activity assay. Normal samples were interpreted correctly by the majority of the participants. However, type 1 vWD samples were wrongly interpreted by 20 to 40% of the participants, which was mainly caused by a discordance in the vWF:RCo/vWF:Ag ratio. It can be concluded that further improvement in the laboratory diagnosis of vWD is necessary.

Clinical and laboratory variability in a cohort of patients diagnosed with type 1 VWD in the United States

“…This is particularly true for the VWF:RCo with its high coefficient of variation. 33, 34 Stress or underlying inflammatory conditions at the time of study entry may have also contributed to increased VWF levels. 35 Hormones and pregnancy can elevate VWF levels.…”

Common VWF exon 28 polymorphisms in African Americans affecting the VWF activity assay by ristocetin cofactor

“…The VWF:RCo assay exploits the capacity of ristocetin to induce a conformational change in VWF that leads to VWF binding to platelet GPIb, but high variability and suboptimal sensitivity compromise the clinical utility of VWF:RCo. [5][6][7] Many factors can influence VWF levels. ABO blood group is a known modifier, with the lowest VWF levels present in those with blood group O.…”

Rapid discrimination of the phenotypic variants of von Willebrand disease

“…New developments in laboratory evaluation for VWF over the past few years have been focused on replacing conventional VWF:RCo testing, because of its high CV and high limit of detection of 10 to 20 IU/ dL, 8,9,32,33 with new automated assays for VWF binding activity to GPIb; however, newer VWF:RCo methods have improved CV to 2% to 8% with automation. 34 A few assays have taken advantage of GPIb binding independent of ristocetin through using recombinant human GPIb with 2 gain-of-function mutations inserted.…”

“…This is highlighted by the VWF ristocetin cofactor assay (VWF:RCo), which is a surrogate VWF activity test that has a high coefficient of variation (CV) up to 50% between laboratories 8, 9 and has impaired ristocetin-binding with a common VWF A1 domain single amino acid substitution, D1472H, in individuals without significant associated bleeding symptoms. 10 To address these issues, development of ristocetin-free assays has been advocated.…”