Hematology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Internal Medicine, Division, Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands.
J Thromb Haemost. 2018 Dec;16(12):2413-2424. doi: 10.1111/jth.14319. Epub 2018 Nov 20.
Essentials It is unclear whether there are differences between von Willebrand factor (VWF) activity assays. We compared the four most used VWF activity assays in 661 von Willebrand disease (VWD) patients. All assays correlated excellently, but a discrepant classification was seen in 20% of patients. Differences between VWF activity assays have a large impact on the classification of VWD. SUMMARY: Background Measuring the ability of von Willebrand factor (VWF) to bind to platelets is crucial for the diagnosis and classification of von Willebrand disease (VWD). Several assays that measure this VWF activity using different principles are available, but the clinical relevance of different assay principles is unclear. Objective To compare the four most widely used VWF activity assays in a large VWD patient population. Methods We measured VWF:RCo (ristocetin to activate VWF + whole platelets), VWF:GPIbR (ristocetin + platelet glycoprotein Ib receptor [GPIb] fragments), VWF:GPIbM (gain-of-function GPIb fragments that bind VWF spontaneously without ristocetin) and VWF:Ab (monoclonal antibody directed against the GPIb binding epitope of VWF to mimic platelets) in 661 VWD patients from the nationwide 'Willebrand in the Netherlands' (WiN) Study. Results All assays correlated excellently (Pearson r > 0.9), but discrepant results led to a different classification for up to one-fifth of VWD patients. VWF:RCo was not sensitive enough to classify 18% of patients and misclassified half of genotypic 2B VWD patients, especially those with p.Arg1306Trp. VWF:GPIbR was more sensitive, accurately classified the vast majority of patients, and was unaffected by the p.Asp1472His variant that causes artificially low VWF:RCo. VWF:GPIbM was the most precise assay but misclassified over a quarter of genotypic 2A, 2B and 3 patients. VWF:Ab, often not considered an actual VWF activity assay, performed at least equally to the other assays with regard to accurate VWD classification. Conclusion Although the different VWF activity assays are often considered similar, differences between assays have a large impact on the classification of VWD.
目的 测量 von Willebrand 因子（VWF）结合血小板的能力对于 von Willebrand 病（VWD）的诊断和分类至关重要。有几种基于不同原理的 VWF 活性测定方法，但不同测定原理的临床相关性尚不清楚。 方法 我们测量了 661 例 VWD 患者中的 4 种最广泛使用的 VWF 活性测定方法，即 VWF:RCo（瑞斯托霉素激活 VWF+全血小板）、VWF:GPIbR（瑞斯托霉素+血小板糖蛋白 Ib 受体 [GPIb] 片段）、VWF:GPIbM（具有功能获得的 GPIb 片段，可在没有瑞斯托霉素的情况下自发结合 VWF）和 VWF:Ab（针对 VWF 与 GPIb 结合表位的单克隆抗体，模拟血小板）。 结果 所有测定方法相关性均极好（Pearson r＞0.9），但多达五分之一的 VWD 患者因结果不一致而导致分类不同。VWF:RCo 不够敏感，无法分类 18%的患者，并且错误分类了一半的 2B 基因型 VWD 患者，尤其是那些携带 p.Arg1306Trp 的患者。VWF:GPIbR 更敏感，准确分类了绝大多数患者，并且不受导致 VWF:RCo 人为降低的 p.Asp1472His 变异的影响。VWF:GPIbM 是最精确的测定方法，但错误分类了超过四分之一的 2A、2B 和 3 基因型患者。VWF:Ab 通常不被认为是一种实际的 VWF 活性测定方法，但在准确分类 VWD 方面与其他测定方法至少同样有效。 结论 尽管不同的 VWF 活性测定方法通常被认为是相似的，但测定方法之间的差异对 VWD 的分类有很大影响。
