Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy. Electronic address: https://twitter.com/OmidSeidi.
Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, Milan, Italy.
J Thromb Haemost. 2024 Aug;22(8):2115-2128. doi: 10.1016/j.jtha.2024.05.006. Epub 2024 May 16.
von Willebrand disease (VWD) is the most frequent inherited bleeding disorder, with an estimated symptomatic prevalence of 1 per 1000 in the general population. VWD is characterized by defects in the quantity, quality, or multimeric structure of von Willebrand factor (VWF), a glycoprotein being hemostatically essential in circulation. VWD is classified into 3 principal types: low VWF/type 1 with partial quantitative deficiency of VWF, type 3 with virtual absence of VWF, and type 2 with functional abnormalities of VWF, being classified as 2A, 2B, 2M, and 2N. A new VWD type has been officially recognized by the ISTH SSC on von Willebrand factor which has also been discussed by the joint ASH/ISTH/NHF/WFH 2021 guidelines (ie, type 1C), indicating patients with quantitative deficiency due to an enhanced VWF clearance. With the advent of next-generation sequencing technologies, the process of genetic diagnosis has substantially changed and improved accuracy. Therefore, nowadays, patients with type 3 and severe type 1 VWD can benefit from genetic testing as much as type 2 VWD. Specifically, genetic testing can be used to confirm or differentiate a VWD diagnosis, as well as to provide genetic counseling. The focus of this manuscript is to discuss the current knowledge on VWD molecular pathophysiology and the application of genetic testing for VWD diagnosis.
血管性血友病（von Willebrand disease，VWD）是最常见的遗传性出血性疾病，在普通人群中，估计有 1/1000 的患者有症状[1,2]。VWD 的特征是血管性血友病因子（von Willebrand factor，VWF）的数量、质量或多聚体结构缺陷，VWF 是循环中止血所必需的糖蛋白[1,2]。VWD 分为 3 种主要类型：VWF 数量减少/1 型，VWF 部分定量缺乏；VWD 3 型，VWF 几乎不存在；VWF 功能异常 2 型，分为 2A、2B、2M 和 2N[1,2]。ISTH SSC 已正式认可一种新的 VWD 类型，即血管性血友病因子（von Willebrand factor），这也在 2021 年 ASH/ISTH/NHF/WFH 联合指南中进行了讨论（即 1C 型），表明患者由于 VWF 清除增强而出现定量缺乏[1,2]。随着下一代测序技术的出现，遗传诊断过程发生了重大变化并提高了准确性[3]。因此，如今，3 型和严重 1 型 VWD 患者与 2 型 VWD 患者一样，可以从基因检测中获益[3]。具体而言，基因检测可用于确认或区分 VWD 诊断，以及提供遗传咨询[3]。本文的重点是讨论 VWD 分子病理生理学的最新知识，以及遗传检测在 VWD 诊断中的应用[3]。
