Diagnosis of von Willebrand disease: An assessment of the quality of testing in North American laboratories

Abstract

Background Laboratory diagnosis of von Willebrand Disease (VWD) is complex. Reliance on laboratory testing can be problematic as different VWD screening panels, assays and methodologies can produce analytic variability in test results. Objectives To compare the degree of imprecision among the VWD assays and within the platelet binding activity (PBA) assays, to determine the consensus among the VWD assays for correct classification of sample results, and to determine consensus among laboratories’ von Willebrand factor (VWF) multimer interpretations and final interpretations of the VWD panels. Patients/Methods Proficiency testing results from the North American Specialized Coagulation Laboratory Association (NASCOLA) submitted by laboratories from 2010 to 2019 for all normal, type (T) 1 VWD and T2 VWD samples were analysed. Results and Conclusions Imprecision was lowest for VWF antigen and highest for collagen binding activity (CBA) with median coefficient of variation (CV) of 12% (interquartile range (IQR) 7%) and 23% (IQR 21%) respectively. Within the VWF PBA assays, the gain‐of‐function mutant GP1b binding (VWF: GP1bM) methods had the least imprecision (CV 9%, IQR 10%). All assays, including the various PBA methods had excellent consensus. The majority of laboratories agreed that normal (median consensus‐82%, IQR 16%) and T1 VWD (median consensus‐100%, IQR 9%) samples had normal multimer distribution. Consensus among laboratories for final interpretations was excellent for normal samples (median 81%, IQR 8%), good for T1 VWD samples (median 59%, IQR 9%), and fair for T2 VWD samples (median 44%, IQR 21%). Consensus on final interpretation decreased as sample complexity increased.

Comparing the quality of testing for von Willebrand disease in different geographic localities

“…As a summary conclusion: whereas NASCOLA identified relative high variability for VWF:CB, it needs to be clarified that this was exclusively using ELISA based methods 1 . RCPAQAP data 2 largely confirms relative high variability for VWF:CB by ELISA, but conversely identifies relative low variability for VWF:CB by CLIA (Figure 1), which is increasing in usage in our geographic locality, 2 but which is unavailable in North America 5,6 .…”

“…4 As a summary conclusion: a. whereas NASCOLA identified relative high variability for VWF:CB, it needs to be clarified that this was exclusively using ELISA based methods. 1 RCPAQAP data 2 largely confirms relative high In type 2 VWD, high CVs are partially due to higher variation per se, and also partially explained by the reporting of many values very close to 0 U/dl, thereby mathematically affecting the calculation of CVs. CLIA based methods tended towards the lowest CVs for all available methods.…”

“…NASCOLA reported the lowest CV for VWF:Ag, followed in turn by VWF:GPIbM (gain of function, mutant glycoprotein Ib [GPIb]), VWF:GPIbR (recombinant GPIb), VWF:Ab (monoclonal antibody based assay), VWF:RCo (ristocetin cofactor), and VWF:CB (collagen binding). Imprecision grew worse from normal to type 1 to type 2 VWD samples 1 . RCPAQAP also reported that assay imprecision grew worse from normal to type 1 to type 2 VWD samples, and that the lowest CVs were evident for VWF:Ag 2 .…”

“…I was very interested to read the recent report from NASCOLA (North American Specialized Coagulation Laboratory Association) containing external quality assessment (EQA) data related to laboratory testing practice for von Willebrand disease (VWD) 1 . These data evaluated findings from laboratories in the United States of America (USA; ∼75% of participants) and Canada (∼25%), from years 2010 to 2019, for a total of 34 samples (10 normal, 13 type 1, 11 type 2 VWD).…”

“…Thirdly, a high proportion of NASCOLA participants (32%) utilise the VWF:Ab assay, this being one of only two FDA-cleared VWF activity assays (the other being VWF:RCo), 6 whereas very few RCPAQAP participants (1%) do so (Table 1 1), both of which show poor performance against the more recently developed VWF:GPIbR and VWF:GPIbM assays (especially in view of the excellent precision and lower limit of detection of the CLIA-based methods), compromises VWD diagnostics in USA. 1,2,[4][5][6][7][8][9] It is therefore hoped that these findings will promote adoption of better diagnostic tests in North America and also positively inform future guidelines for diagnosis of VWD. 5,10…”