Hematology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands;
Einthoven Laboratory for Experimental Vascular Medicine, Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands;
Blood. 2015 May 7;125(19):3006-13. doi: 10.1182/blood-2014-09-603241. Epub 2015 Feb 11.
The ratios between von Willebrand factor propeptide (VWFpp) or factor VIII activity (
C) and VWF antigen (VWF:Ag) reflect synthesis, secretion, and clearance of VWF. We aimed to define the pathophysiology of 658 patients with type 1, 2, or 3 von Willebrand disease (VWD) with VWF levels ≤30 U/dL from the Willebrand in The Netherlands (WiN) study using the VWFpp/VWF:Ag and
C/VWF:Ag ratios. We evaluated the use of VWFpp in the classification and diagnosis of VWD. On the basis of the ratios, reduced VWF synthesis was observed in 18% of type 1 and only 2% of type 2 patients. A significant proportion of type 3 patients had detectable VWFpp (41%). These patients had a lower bleeding score than type 3 patients who had a complete absence of VWF:Ag and VWFpp (14.0 vs 19.5; P = .025). The majority of these patients had missense mutations with rapid VWF clearance, whereas type 3 patients with no VWFpp were homozygous for null alleles. In conclusion, VWFpp identified severe type 1 VWD with very low VWF levels in patients who had previously been classified as type 3 VWD. This study underlines the clinical significance of the VWFpp assay in the diagnosis and classification of VWD.
血管性血友病因子前肽（VWFpp）或因子 VIII 活性（FVIII：C）与血管性血友病因子抗原（VWF：Ag）的比值反映了 VWF 的合成、分泌和清除。我们旨在使用 VWFpp/VWF：Ag 和 FVIII：C/VWF：Ag 比值来定义 WiN 研究中 658 例 VWF 水平≤30 U/dL 的 1、2 或 3 型血管性血友病（VWD）患者的病理生理学。我们评估了 VWFpp 在 VWD 分类和诊断中的应用。根据这些比值，发现 18%的 1 型和仅 2%的 2 型患者存在 VWF 合成减少。相当一部分 3 型患者可检测到 VWFpp（41%）。这些患者的出血评分低于 VWF：Ag 和 VWFpp 完全缺失的 3 型患者（14.0 与 19.5；P=.025）。这些患者中大多数存在 VWF 清除率快的错义突变，而无 VWFpp 的 3 型患者则为无功能等位基因的纯合子。总之，VWFpp 在前被归类为 3 型 VWD 的患者中发现了 VWF 水平极低的严重 1 型 VWD。本研究强调了 VWFpp 检测在 VWD 诊断和分类中的临床意义。
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