Evaluation of a new commercial method for von Willebrand factor multimeric analysis

Crist, Ronda A.; Heikal, Nahla; Rodgers, George M.; Grenache, David G.; Smock, Kristi J.

doi:10.1111/ijlh.12869

Cited by 14 publications

(28 citation statements)

References 20 publications

(81 reference statements)

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“…The Hydrasys VWF multimer system has undergone additional evaluation by our laboratory and several other groups 18–24 . Results in general reflect positively for the methodology, albeit with already‐noted limitations 18,20 .…”

Section: Vwd Type Classification Description Vwf:ag Vwf:gpib Bindinga Vwf:cb Fviii:c Multimers Gpib Binding/agb Cb/agb Fviii/vwfb Commentmentioning

confidence: 81%

Classification of von Willebrand disease in the context of modern contemporary von Willebrand factor testing methodologies

Favaloro

2020

Research and Practice in Thrombosis and Haemostasis

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disease (VWD) is reportedly the most common inherited bleeding disorder, potentially affecting up to 1% of the population according to epidemiologic data, although numbers based on presentation to clinics are closer to 0.1%. 1 VWD arises from defects and/or deficiency of von Willebrand factor (VWF), and laboratory testing assists clinical exclusion or diagnosis. [2][3][4][5] Contemporary laboratory assays comprise VWF antigen (VWF:Ag), markers of VWF activity, and factor VIII activity (FVIII:C), 2-7 using various methods.There are many VWF activity assays, especially those reflective of glycoprotein Ib (GPIb) binding (including classical ristocetin cofactor [VWF:RCo]), and for which the VWF/VWD Scientific Standardisation Committee (SSC) of the ISTH has recommended revised nomenclature. 5,7 VWF:RCo assays using platelets, ristocetin, and native GPIb remain VWF:RCo, but those using other solid-phase particles and recombinant GPIb are termed VWF:GPIbR. 5,7 Additional gainof-function VWF assays using recombinant GPIb mutations reflect VWF:GPIb binding assays similar to VWF:RCo and VWF:GPIbR but that do not employ ristocetin are termed VWF:GPIbM. 5,7-9 Another distinct category of VWF activity assay is the collagen binding assay (VWF:CB). 5,10 Assessment of VWF multimers by gel electrophore-This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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Section: Vwd Type Classification Description Vwf:ag Vwf:gpib Bindinga Vwf:cb Fviii:c Multimers Gpib Binding/agb Cb/agb Fviii/vwfb Commentmentioning

confidence: 81%

Classification of von Willebrand disease in the context of modern contemporary von Willebrand factor testing methodologies

Favaloro

2020

Research and Practice in Thrombosis and Haemostasis

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“…On the other hand, Bowyer et al 17 and a recent report by Favaloro et al 39 published quantitative HMWM loss in some of the type 2M patients. However, Crist et al 18 and Pikta et al 19 do not mention type 2M VWD in their studies about H5/11VWM.…”

Section: Discussionmentioning

confidence: 94%

Improving diagnosis of von Willebrand disease: Reference ranges for von Willebrand factor multimer distribution

Vangenechten

Gadisseur

2020

Research and Practice in Thrombosis and Haemostasis

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Background Phenotypic von Willebrand disease (VWD) classification requires multiple tests including analysis of multimeric distributions von Willebrand factor (VWF) and evaluation of its structure. VWF multimer analysis is labor intensive, nonstandardized, and limited to specialized laboratories. A commercial semiautomatic assay, HYDRAGEL VW multimer assay (H5/11VWM, Sebia), has become available. Objectives Establishment of reference ranges for H5/11VWM to improve VWD classification. Methods Implementation validation, establishment and validation of normal and pathological reference intervals (NRIs/PRIs), comparison with in‐house method using 40 healthy volunteers and 231 VWD patients. Results Qualitative and quantitative validation of NRI obtained sensitivity of 88% and 79%, respectively, for type 2. Comparison of the two methods showed an overall concordance of 86% with major conflicting results in all atypical 2B (n = 7) and 50% 2M‐GPIb (n = 41) showing quantitative and qualitative multimeric loss, that was not detected with in‐house method. We were able to use established PRIs, with 73% validity in type 2 cases, to distinguish individual type 2A subtypes (IIA, IIC, IID, IIE) from 2M and 2B. Conclusion H5/11VWM could be used for all clinical purposes because its reliability and its rapid and accurate diagnostic ability and reduced observer bias. Although H5/11VWM cannot evaluate triplet structures, we were able to define 2A subtypes by stripping back to the percentage of intermediate/high‐molecular‐weight multimers. H5/11HWM could be an efficient and widely available alternative for the “gold standard” technique.

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“…We have previously reported on this multimer assay from the perspective of methodology validation, primarily via visual inspection of multimer patterns, but had not reported quantitative multimer separation vs quantitative VWF data. There have been few other reports on this method in the literature . Although some assessed multimer quantification according to manufacturer recommended groupings, none assessed this numerically in comparison with VWF activity/Ag ratios (as per our study), and none had assessed the chemiluminescence VWF procedures.…”

Section: Discussionmentioning

confidence: 96%

“…). Other workers using in house multimer systems use different separation approaches, for example the first five bands as LMWM, followed by bands 6‐10 as IMWM, and then finally bands >10 as HMWM.…”

Section: Discussionmentioning

confidence: 99%

Comparative assessment of von Willebrand factor multimers vs activity for von Willebrand disease using modern contemporary methodologies

et al. 2020

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Introduction Diagnosis of von Willebrand disease (VWD) is challenging due to heterogeneity of VWD and test limitations. Many von Willebrand factor (VWF) assays are utilized, including antigen (Ag), activity and multimer analysis. Activity assays include ristocetin cofactor using platelets (VWF:RCo) or other particles incorporating recombinant glycoprotein I (‘VWF:GPIbR’), or other GPI binding assays using gain‐of‐function mutations (‘VWF:GPIbM’), or collagen binding (VWF:CB). Aim To comparatively evaluate modern contemporary VWF activity assays vs VWF multimer analysis using modern contemporary methods. Materials and methods Several VWF activity assays (VWF:RCo, VWF:GPIbR, VWF:GPIbM, VWF:CB) assessed (typically as a ratio against VWF:Ag) against a new semi‐automated procedure for different types of VWD (1, 3, 2A, 2B, 2M), plus control material (n = 580). The evaluation also focussed on relative loss of high and very high molecular weight multimers (HMWM and VHMWM) by densitometric scanning. Results All evaluated VWF activity/Ag ratios showed high correlation to the presence/absence of HMWM and VHMWM, although VWF:CB/Ag and VWF:GPIbR/Ag ratios using an automated chemiluminescence method yielded highest correlation coefficients (r = .909 and .874, respectively, for HMWM). Use of the investigative procedure (VHMWM) identified fewer false positives for ‘loss’ in type 1 VWD. Conclusions This comparative investigation identified that new automated chemiluminescence VWF activity assays best identified relative loss or presence of HMWM and VHMWM according to activity to Ag ratios and an alternative investigative method for identifying VHMWM in multimer testing for a new commercial multimer method may lead to fewer false identifications of HMW loss in type 1 VWD.

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Evaluation of a new commercial method for von Willebrand factor multimeric analysis

Abstract: The commercial multimer method is a streamlined test that demonstrates comparable performance characteristics to our current laboratory-developed method and that provides the advantage of both electrophoresis gels and densitometry scans to aid interpretation.

Cited by 14 publications

References 20 publications

Classification of von Willebrand disease in the context of modern contemporary von Willebrand factor testing methodologies

Classification of von Willebrand disease in the context of modern contemporary von Willebrand factor testing methodologies

Improving diagnosis of von Willebrand disease: Reference ranges for von Willebrand factor multimer distribution

Comparative assessment of von Willebrand factor multimers vs activity for von Willebrand disease using modern contemporary methodologies

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