Intraindividual variability of von Willebrand factor and the need for repeated testing

Abstract

Background: 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 × 103 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. Objectives: 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. Methods: 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 (CVnonanalytical). Results: We found a CVnonanalytical of 22.03% (n = 252), 24.10% (n = 333), and 24.07 (n = 58) for VWF:Ag, VWF:GPIbR, and VWF:CB, respectively. We did not find substantial differences in CVnonanalytical 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 × 103 IU/L, 0.66 × 103 IU/L, and 0.88 × 103 IU/L for VWF:Ag, VWF:GPIbR, and VWF:CB, respectively. Conclusion: 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.

Keywords

• reproducibility of results
• von Willebrand factor
• von Willebrand diseases