Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland; National Coagulation Centre, St James's Hospital, Dublin, Ireland; and National Children's Research Centre, Our Lady's Children's Hospital Crumlin, Dublin, Ireland.
Blood Adv. 2020 Jul 14;4(13):3191-3199. doi: 10.1182/bloodadvances.2020002038.
von Willebrand disease (VWD) constitutes the most common inherited human bleeding disorder. Partial quantitative von Willebrand factor (VWF) deficiency is responsible for the majority of VWD cases. International guidelines recommend that patients with mild to moderate reductions in plasma VWF antigen (VWF:Ag) levels (typically in the range of 30-50 IU/dL) should be diagnosed with low VWF. Over the past decade, a series of large cohort studies have provided significant insights into the biological mechanisms involved in type 1 VWD (plasma VWF:Ag levels <30 IU/dL). In striking contrast, however, the pathogenesis underpinning low VWF has remained poorly understood. Consequently, low VWF patients continue to present significant clinical challenges with respect to genetic counseling, diagnosis, and management. For example, there is limited information regarding the relationship between plasma VWF:Ag levels and bleeding phenotype in subjects with low VWF. In addition, it is not clear whether patients with low VWF need treatment. For those patients with low VWF in whom treatment is deemed necessary, the optimal choice of therapy remains unknown. However, a number of recent studies have provided important novel insights into these clinical conundrums and the molecular mechanisms responsible for the reduced levels observed in low VWF patients. These emerging clinical and scientific findings are considered in this review, with particular focus on pathogenesis, diagnosis, and clinical management of low VWF.
血管性血友病（von Willebrand disease，VWD）是最常见的遗传性人类出血性疾病。部分定量 von Willebrand 因子（von Willebrand factor，VWF）缺乏是大多数 VWD 病例的原因。国际指南建议，血浆 VWF 抗原（VWF:Ag）水平轻度至中度降低（通常在 30-50 IU/dL 范围内）的患者应诊断为 VWF 降低。在过去十年中，一系列大型队列研究为 1 型 VWD（血浆 VWF:Ag 水平 <30 IU/dL）的生物学机制提供了重要的见解。然而，与 1 型 VWD 形成鲜明对比的是，低 VWF 的发病机制仍知之甚少。因此，低 VWF 患者在遗传咨询、诊断和管理方面仍然存在重大临床挑战。例如，关于低 VWF 患者血浆 VWF:Ag 水平与出血表型之间的关系，信息有限。此外，不清楚低 VWF 患者是否需要治疗。对于那些认为需要治疗的低 VWF 患者，最佳治疗选择仍不清楚。然而，最近的一些研究为这些临床难题和低 VWF 患者观察到的水平降低的分子机制提供了重要的新见解。本综述考虑了这些新的临床和科学发现，特别关注低 VWF 的发病机制、诊断和临床管理。
