A comparative analysis of different automated von Willebrand factor glycoprotein Ib‐binding activity assays in well typed von Willebrand disease patients. (6th June 2018) - Vangenechten, I.
Abstract : Essentials Von Willebrand ristocetin cofactor activity (VWF:RCo) is not a completely reliable assay. Three automated VWF activity assays were compared within a von Willebrand disease (VWD) cohort. Raw values for all three assays were virtually the same. An overall problem within type 2A/IIE VWD using VWF:GPIb‐binding activity/VWF:Ag was observed. Summary: Background: von Willebrand disease (VWD) is an inherited bleeding disorder caused by quantitative (type 1 and 3) or qualitative (type 2) von Willebrand factor (VWF) defect. VWD diagnosis and classification require numerous laboratory tests. VWF: glycoprotein Ib (GPIb)‐binding activity assays are used to distinguish type 1 from type 2 VWD. Objectives: Three different automated VWF:GPIb‐binding activity assays were compared. Patients and methods: BC‐VWF:RCo (Siemens Healthcare Diagnostics), HemosIL ® VWF:RCo (Instrumentation Laboratory) and INNOVANCE ® VWF:Ac (Siemens Healthcare Diagnostics) were performed in a well typed VWD cohort ( n = 142). Results: Based on the three most used VWD parameters (FVIII:C, VWF:Ag and VWF:GPIb‐binding activity) and using a cut‐off of <0.70 for type 2 VWD revealed sensitivity and specificity of, respectively, 92% and 72.4% for VWF:RCo/VWF:Ag, 84% and 89.7% for VWF:GPIbR/VWF:Ag, and 92% and 85.1% for VWF:GPIbM/VWF:Ag, whereas a lowered cut‐off of < 0.60 resulted in reduced sensitivity with increased specificity for all assays. Conclusion: VWD classification based on FVIII:C, VWF:Ag and VWF:GPIb‐binding activity revealed an overall problem with normal VWF:GPIb‐binding activity/VWF:Ag within type 2, especially type 2A/IIE. Although all assays were practically identical, BC‐VWF:RCo had higher %CV compared with both new assays but comparable lower limit of quantification (LLOQ) ~4 IU dL −1 . No clear improved distinction between type 1 and 2 VWD with new assays was seen. BC‐VWF:RCo and HemosIL ® are ristocetin dependent, whereas INNOVANCE ® does not rely upon ristocetin and is not influenced by VWF polymorphisms increasing VWF:GPIb‐binding activity levels. INNOVANCE ® seems to be the best choice as a first‐line VWF:GPIb‐binding activity assay, providing the best balance between sensitivity and specificity for type 2 VWD.