Department of Pediatrics, Division of Hematology/Oncology, Washington University School of Medicine, St. Louis, Missouri, USA.
Department of Oncology, Center for Bleeding Disorders and Coagulation, Careggi University Hospital, Florence, Italy.
Haemophilia. 2022 May;28 Suppl 4(Suppl 4):11-17. doi: 10.1111/hae.14547.
Progress in both basic and translational research into the molecular mechanisms of VWD can be seen in multiple fields.
In the past several decades, knowledge of the underlying pathogenesis of von Willebrand disease (VWD) has increased tremendously, thanks in no small part to detailed genetic mapping of the von Willebrand Factor (VWF) gene and advances in genetic and bioinformatic technology. However, these advances do not always easily translate into improved management for patients with VWD and low-VWF levels.
For example, the treatment of pregnant women with VWD both pre- and postpartum can be complicated. While knowledge of the VWF genotype at some amino acid positions can aid in knowledge of who may be at increased risk of thrombocytopenia or insufficient increase in VWF levels during pregnancy, in many cases, VWF levels and bleeding severity is highly heterogeneous, making monitoring recommended during pregnancy to optimize treatment strategies. VWF AND COVID-19: New challenges related to the consequences of dysregulation of hemostasis continue to be discovered. The ongoing COVID-19 pandemic has highlighted that VWF has additional biological roles in the regulation of inflammatory disorders and angiogenesis, disruption of which may contribute to COVID-19 induced vasculopathy. Increased endothelial cell activation and Weibel-Palade body exocytosis in severe COVID-19 lead to markedly increased plasma VWF levels. Coupled with impairment of normal ADAMTS13 multimer regulation, these data suggest a role for VWF in the pathogenesis underlying pulmonary microvascular angiopathy in severe COVID-19.
With the increased affordability and availability of next-generation sequencing techniques, as well as a push towards a multi-omic approach and personalized medicine in human genetics, there is hope that translational research will improve VWD patient outcomes.
在基础和转化研究领域，人们对血管性血友病（VWD）分子机制的研究取得了进展。
VWD 的遗传学：在过去几十年中，由于对血管性血友病因子（VWF）基因进行了详细的遗传定位以及遗传和生物信息学技术的进步，对血管性血友病（VWD）发病机制的认识有了极大的提高。然而，这些进展并不总能轻易转化为 VWD 患者和低 VWF 水平患者管理的改善。
VWD 和妊娠：例如，VWD 孕妇在妊娠前和产后的治疗可能很复杂。虽然某些氨基酸位置的 VWF 基因型知识可以帮助了解谁可能有更高的血小板减少或妊娠期间 VWF 水平增加不足的风险，但在许多情况下，VWF 水平和出血严重程度高度异质，因此建议在妊娠期间进行监测以优化治疗策略。
VWF 和 COVID-19：与止血失调的后果相关的新挑战继续被发现。持续的 COVID-19 大流行强调了 VWF 在调节炎症障碍和血管生成中的额外生物学作用，其破坏可能导致 COVID-19 引起的血管病变。严重 COVID-19 中内皮细胞的过度激活和 Weibel-Palade 体胞吐导致血浆 VWF 水平显著增加。加上正常 ADAMTS13 多聚体调节受损，这些数据表明 VWF 在严重 COVID-19 中肺微血管血管病的发病机制中起作用。
随着下一代测序技术的普及和可负担性的提高，以及人类遗传学中向多组学方法和个性化医学的推动，人们希望转化研究能改善 VWD 患者的预后。
