Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University.
Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta and Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA.
Curr Opin Hematol. 2023 May 1;30(3):86-92. doi: 10.1097/MOH.0000000000000755. Epub 2023 Jan 12.
This review provides an update on the pathophysiology of sickle cell disease (SCD) with a particular focus on the dysregulation of the von Willebrand factor (VWF) - ADAMTS13 axis that contributes to its pathogenesis. In discussing recent developments, we hope to encourage new and ongoing discussions surrounding therapeutic targets for SCD.
Within the last 5 years, the role of VWF in the pathophysiology of SCD has been further elucidated and is now a target of study in ongoing clinical trials.
The pathophysiology of SCD is multifaceted, as it involves systemwide vascular activation, altered blood rheology, and the activation of immune responses and coagulative pathways. The presence of VWF in excess in SCD, particularly in its largest multimeric form, greatly contributes to its pathogenesis. Understanding the molecular mechanisms that underly the presence of large VWF multimers in SCD will provide further insight into the pathogenesis of SCD and provide specific targets for therapy.
本篇综述提供了镰状细胞病（SCD）病理生理学的最新进展，特别关注导致其发病机制的血管性血友病因子（VWF）-ADAMTS13 轴的失调。在讨论最新进展时，我们希望鼓励围绕 SCD 的治疗靶点进行新的和持续的讨论。
在过去的 5 年中，VWF 在 SCD 病理生理学中的作用得到了进一步阐明，目前正在进行的临床试验中对其进行了研究。
SCD 的病理生理学是多方面的，因为它涉及全身性血管激活、血液流变性改变以及免疫反应和凝血途径的激活。SCD 中存在大量 VWF，尤其是其最大的多聚体形式，极大地促成了其发病机制。了解 SCD 中存在大 VWF 多聚体的分子机制将进一步深入了解 SCD 的发病机制，并为治疗提供具体靶点。
