von Willebrand Factor Assay Proficiency Testing Continued

Favaloro, Emmanuel J.

doi:10.1309/ajcp65jxehsjdhur

Cited by 7 publications

(6 citation statements)

References 11 publications

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“…We have previously shown that, in discrimination of type 2 vs. type 1 VWD cases, the VWF:RCo and VWF:CB assays (and thus the RCo/Ag and CB/Ag ratios) generally perform better than the VWF:Act assay (and Act/Ag ratios) [21]. Interestingly, the NASCOLA study also identified better performance of the VWF:CB assay than either the VWF:Act or VWF:RCo assay in the context of such discrimination [22,30,31]. The current study expands on these findings, and in part may also explain possible reasons behind them, given that the VWF:Act assay appears to be less sensitive to the loss of HMW VWF than both the VWF:RCo and VWF:CB assays.…”

Section: Discussionsupporting

confidence: 71%

Differential sensitivity of von Willebrand factor (VWF) ‘activity’ assays to large and small VWF molecular weight forms: a cross‐laboratory study comparing ristocetin cofactor, collagen‐binding and mAb‐based assays

Favaloro

Bonar

Chapman

et al. 2012

Journal of Thrombosis and Haemostasis

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Summary. Background: von Willebrand disease (VWD), the most common inherited bleeding disorder, is caused by deficiencies and/or defects in von Willebrand factor (VWF). An effective diagnostic and VWD typing strategy requires plasma testing for factor VIII, and VWF antigen plus one or more VWF ‘activity’ assays. VWF activity is classically assessed by using VWF ristocetin cofactor activity (VWF:RCo), although VWF collagen‐binding (VWF:CB) and VWF mAb‐based (VWF activity [VWF:Act]) assays are used by some laboratories. Objective: To perform a cross‐laboratory study to specifically evaluate these three VWF activity assays for comparative sensitivity to loss of high molecular weight (HMW) VWF, representing the form of VWF that is most functionally active and that is absent in some types of VWD, namely 2A and 2B. Methods: A set of eight samples, including six selectively representing stepwise reduction in HMW VWF, were tested by 51 different laboratories using a variety of assays. Results: The combined data showed that the VWF:CB and VWF:RCo assays had higher sensitivity to the loss of HMW VWF than did the VWF:Act assay. Moreover, within‐method analysis identified better HMW VWF sensitivity of some VWF:CB assays than of others, with all VWF:CB assays still showing better sensitivity than the VWF:Act assay. Differences were also identified between VWF:RCo methodologies on the basis of either platelet aggregometry or as performed on automated analyzers. Conclusions: We believe that these results have significant clinical implications for the diagnosis of VWD and monitoring of its therapy, as well as for the future diagnosis and therapy monitoring of thrombotic thrombocytopenic purpura.

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Section: Discussionsupporting

confidence: 71%

Differential sensitivity of von Willebrand factor (VWF) ‘activity’ assays to large and small VWF molecular weight forms: a cross‐laboratory study comparing ristocetin cofactor, collagen‐binding and mAb‐based assays

Favaloro

Bonar

Chapman

et al. 2012

Journal of Thrombosis and Haemostasis

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“…However, we distributed uniform, lyophilised specimens to laboratories which eliminates many of the traditional pre‐analytical variables encountered by laboratories. Third, the use of lyophilised plasma samples may cause a loss of high molecular weight VWF multimers, thereby modifying the proficiency samples from what was intended, however this is unlikely to be a substantial issue due to improvements in lyophilisation techniques, with better pH control and stabilisers 16,17 . Fourth, as the mutation analysis data on the distributed VWD samples was not available, it is unclear the specific mutations played a role in the variation of results.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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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.

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“…The VWF:CB, as supplemental to VWF:RCo (or perhaps increasingly now a direct GPIb binding assay), can also act as “surrogates” for VWF multimers (see Table ) . Moreover, it is often under‐recognised that multimer analysis is itself associated with an even worse VWD diagnostic error rate than VWF:RCo . In our experience, RIPA analysis and use of DDAVP trial data , generally provides more value in VWD diagnostics than multimer analysis.…”

Section: Resultsmentioning

confidence: 99%

Utility of the von Willebrand factor collagen binding assay in the diagnosis of von Willebrand disease

Favaloro

2016

American J Hematol

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von Willebrand Disease (VWD) is the most common inherited bleeding disorder and also arises as an acquired defect (AVWS). VWD and AVWS are due to quantitative deficiencies and/or qualitative defects in von Willebrand factor (VWF), an adhesive plasma protein with multiple activities. Diagnosis of VWD is problematic, being subject to overdiagnosis, underdiagnosis, and misdiagnosis. This is largely due to limitations in current test procedures and an over‐reliance on these imperfect test systems for clinical diagnosis. VWF essentially acts to assist in the formation of a platelet thrombus to stop blood loss from sites of injury, achieving this by binding to platelets (primarily through the glycoprotein Ib receptor), binding to subendothelial matrix components (primarily collagen), and binding to factor VIII (FVIII), thus protecting FVIII from degradation and enabling its delivery to sites of vascular injury. VWD is classified into six separate types, which may each be differentially managed therapeutically, and this underscores the importance of a correct diagnosis. The current report concisely reviews the utility of a relatively underutilised assay, the VWF collagen binding assay (VWF:CB), in facilitating the correct diagnosis and typing of VWD. In particular, if laboratories do not utilise the VWF:CB, then (i) type 2M VWD will continue to be missed, and/or misdiagnosed as types 2A or 1 VWD, and (ii) types 2A, 2B and PT‐VWD will continue to be missed, or else be misdiagnosed as type 1 VWD or ITP. Am. J. Hematol. 92:114–118, 2017. © 2016 Wiley Periodicals, Inc.

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von Willebrand Factor Assay Proficiency Testing Continued

Cited by 7 publications

References 11 publications

Differential sensitivity of von Willebrand factor (VWF) ‘activity’ assays to large and small VWF molecular weight forms: a cross‐laboratory study comparing ristocetin cofactor, collagen‐binding and mAb‐based assays

Differential sensitivity of von Willebrand factor (VWF) ‘activity’ assays to large and small VWF molecular weight forms: a cross‐laboratory study comparing ristocetin cofactor, collagen‐binding and mAb‐based assays

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

Utility of the von Willebrand factor collagen binding assay in the diagnosis of von Willebrand disease

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