Kirkeby Malene Helligsø, Højbjerg Johanne Andersen, Abildgaard Anders Mønsted, Larsen Julie Brogaard
Department of Clinical Biochemistry, Aarhus University Hospital, Denmark.
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Res Pract Thromb Haemost. 2025 May 17;9(4):102889. doi: 10.1016/j.rpth.2025.102889. eCollection 2025 May.
Diagnosing von Willebrand disease (VWD) is complicated by intraindividual variation of von Willebrand factor (VWF). Current guidelines define VWD as VWF antigen (VWF:Ag) or VWF activity of <0.30 or <0.50 × 10 IU/L depending on the presence of bleeding symptoms. However, there is no consensus on whether repeated testing is necessary in patients with VWF levels close to the cutoff.
This study aimed to examine the intraindividual variation of VWF antigen (VWF:Ag), platelet-binding activity (VWF:GPIbR), and collagen-binding activity (VWF:CB) by use of routine patient data and to define cutoffs for reliably excluding VWD based on a single sample.
In this cross-sectional study, we extracted patient results of VWF:Ag, VWF:GPIbR, and VWF:CB analyzed at the Department of Clinical Chemistry, Aarhus University Hospital, from January 2013 to January 2024 and calculated total and nonanalytical coefficient of variation (CV).
We found a CV of 22.03% ( = 252), 24.10% ( = 333), and 24.07 ( = 58) for VWF:Ag, VWF:GPIbR, and VWF:CB, respectively. We did not find substantial differences in CV across subgroups based on sex, age, and VWF levels. Furthermore, we estimated a method-specific cutoff to exclude VWD based on a single blood sample at 0.67 × 10 IU/L, 0.66 × 10 IU/L, and 0.88 × 10 IU/L for VWF:Ag, VWF:GPIbR, and VWF:CB, respectively.
We found considerable intraindividual VWF variation in patients referred for VWF testing. Our results confirm that repeated testing is crucial when VWF is low in the normal range to prevent false rejection of a true VWD diagnosis.
血管性血友病因子（VWF）的个体内变异使血管性血友病（VWD）的诊断变得复杂。当前指南将VWD定义为根据出血症状的有无，VWF抗原（VWF:Ag）或VWF活性<0.30或<0.50×10 IU/L。然而，对于VWF水平接近临界值的患者是否需要重复检测，尚无共识。
本研究旨在利用常规患者数据检查VWF抗原（VWF:Ag）、血小板结合活性（VWF:GPIbR）和胶原结合活性（VWF:CB）的个体内变异，并确定基于单个样本可靠排除VWD的临界值。
在这项横断面研究中，我们提取了2013年1月至2024年1月在奥胡斯大学医院临床化学科分析的VWF:Ag、VWF:GPIbR和VWF:CB的患者结果，并计算了总变异系数和非分析变异系数（CV）。
我们发现VWF:Ag、VWF:GPIbR和VWF:CB的CV分别为22.03%（n = 252）、24.10%（n = 333）和24.07（n = 58）。我们未发现基于性别、年龄和VWF水平的亚组间CV有实质性差异。此外，我们估计基于单个血样排除VWD的方法特异性临界值分别为VWF:Ag 0.67×10 IU/L、VWF:GPIbR 0.66×10 IU/L和VWF:CB 0.88×10 IU/L。
我们发现接受VWF检测的患者存在相当大的个体内VWF变异。我们的结果证实，当VWF处于正常范围低值时，重复检测对于防止真正的VWD诊断被错误排除至关重要。
