False normal von Willebrand factor activity by monoclonal antibody-based ELISA in a patient with type 2A(IID) von Willebrand disease

Ahmad, Sufian S.; Ptashkin, Beverly; Digiovanni, Cara; Cines, Douglas B.; Konkle, Barbara A.; Cuker, Adam

doi:10.1160/th11-07-0484

Cited by 4 publications

(4 citation statements)

References 17 publications

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“…The VWF:CB assay, first described in 1986 [9], represents another activity of VWF, namely its ability to bind to collagen, a subendothelial matrix component. The VWF:Act assay, first reported as an immunoradiometric assay in 1985, and later as an ELISA assay, is now most commonly performed with an immunolatex procedure [10–13,16,17].…”

Section: Discussionmentioning

confidence: 99%

“…mAb‐based VWF:Act immunoassays, originally described in 1995, utilize a mAb directed against a functional epitope on VWF as the capture and/or detection antibody [3,10–12]. Later independent validation studies suggested inferiority of the commercial mAb ELISA‐based assays to VWF:RCo and VWF:CB or even in‐house mAb‐based ELISA assays for discrimination of HMW VWF‐deficient VWD types such as 2A and 2B [13–15], and as most recently highlighted for a case study of type 2A VWD [16]. The latex agglutination assay developed by Instrumentation Laboratory is currently the most popular mAb‐based VWF:Act assay [17,18].…”

Section: Introductionmentioning

confidence: 99%

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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: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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“…Obviously, having the sequence of VWF from patients and families is advantageous to establish a more reliable diagnosis and also to detect various degrees of the disease that would otherwise be missed. The VWD phenotypical study presents several drawbacks such as low sensitivity of VWF:RCo and discrepancies of results obtained with different VWF activity assays (14,27,(45)(46)(47). In theory, as yet undetected mutations other than collagen IV and VI may be associated with VWD in patients with a mild bleeding phenotype in whom current routine laboratory investigation is normal.…”

Section: The Role Of Ngs In Vwd Diagnosismentioning

confidence: 99%

“…Also some tests, such as ristocetin-induced platelet agglutination (RIPA) and VWF multimeric analysis, are not generally available in all laboratories (13). Depending on the assay used some mutations may show normal values (14), or can only be detected by using types IV and VI collagen in patients who present with a clear mild bleeding history (15). It is also likely that other potential VWF defects causing VWD may remain undiagnosed (16).…”

Section: Introductionmentioning

confidence: 99%

Molecular and clinical profile of von Willebrand disease in Spain (PCM–EVW–ES): Proposal for a new diagnostic paradigm

Batlle¹,

Pérez‐Rodríguez²,

Corrales³

et al. 2016

Thromb Haemost

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The diagnosis of von Willebrand disease (VWD) remains difficult in a significant proportion of patients. A Spanish multicentre study investigated a cohort of 556 patients from 330 families who were analysed centrally. VWD was confirmed in 480. Next generation sequencing (NGS) of the whole coding VWF was carried out in all recruited patients, compared with the phenotype, and a final diagnosis established. A total of 238 different VWF mutations were found, 154 were not included in the Leiden Open Variation Database (LOVD). Of the patients, 463 were found to have VWF mutation/s. A good phenotypic/genotypic association was estimated in 96.5% of the patients. One hundred seventy-four patients had two or more mutations. Occasionally a predominant phenotype masked the presence of a second abnormality. One hundred sixteen patients presented with mutations that had previously been associated with increased von Willebrand factor (VWF) clearance. RIPA unavailability, central phenotypic results disagreement and difficult distinction between severe type 1 and type 3 VWD prevented a clear diagnosis in 70 patients. The NGS study facilitated an appropriate classification in 63 of them. The remaining seven patients presented with a VWF novel mutation pending further investigation. In five patients with a type 3 and two with a type 2A or 2B phenotype with no mutation, an acquired von Willebrand syndrome (AVWS) was suspected/confirmed. These data seem to support NGS as a first line efficient and faster paradigm in VWD diagnosis.

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Diagnostic challenges in von Willebrand disease. Report of two cases with emphasis on multimeric and molecular analysis

et al. 2020

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False normal von Willebrand factor activity by monoclonal antibody-based ELISA in a patient with type 2A(IID) von Willebrand disease

Cited by 4 publications

References 17 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

Molecular and clinical profile of von Willebrand disease in Spain (PCM–EVW–ES): Proposal for a new diagnostic paradigm

Diagnostic challenges in von Willebrand disease. Report of two cases with emphasis on multimeric and molecular analysis

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