TY - JOUR
T1 - Differential sensitivity of von Willebrand factor (VWF) 'activity' assays to large and small VWF molecular weight forms
T2 - a cross-laboratory study comparing ristocetin cofactor, collagen-binding and mAb-based assays
AU - Favaloro, E J
AU - Bonar, R
AU - Chapman, K
AU - Meiring, M
AU - Funk Adcock, D
N1 - © 2012 International Society on Thrombosis and Haemostasis.
PY - 2012/6
Y1 - 2012/6
N2 - 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.
AB - 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.
KW - Antibodies, Monoclonal
KW - Biomarkers/blood
KW - Calibration
KW - Clinical Laboratory Techniques/standards
KW - Collagen
KW - Drug Monitoring/methods
KW - Enzyme-Linked Immunosorbent Assay/standards
KW - Humans
KW - Molecular Weight
KW - Observer Variation
KW - Predictive Value of Tests
KW - Reference Standards
KW - Reproducibility of Results
KW - Ristocetin
KW - Sensitivity and Specificity
KW - von Willebrand Diseases/blood
KW - von Willebrand Factor/analysis
U2 - 10.1111/j.1538-7836.2012.04729.x
DO - 10.1111/j.1538-7836.2012.04729.x
M3 - Article
C2 - 22487084
SN - 1538-7836
VL - 10
SP - 1043
EP - 1054
JO - Journal of Thrombosis and Haemostasis
JF - Journal of Thrombosis and Haemostasis
IS - 6
ER -