Department of Cell Therapy and Hematology, Hemophilia and Thrombosis Center, San Bortolo Hospital, Vicenza, Italy.
Curr Opin Hematol. 2013 Sep;20(5):424-9. doi: 10.1097/MOH.0b013e328363c11f.
Von Willebrand disease (VWD) is an autosomally inherited bleeding disorder caused by a deficiency or abnormality of von Willebrand factor (VWF). VWF is a multimeric adhesive protein produced mainly by the endothelial cells. VWF is crucial in primary hemostasis because it promotes platelet adhesion to the subendothelium at the sites of vascular injury and in coagulation because VWF is the carrier of factor VIII. VWD is highly heterogeneous because the molecular mechanisms underlying the different clinical and laboratory phenotypes may be complex. VWD is classified into quantitative deficiencies of VWF (type 1 and type 3 VWD) and qualitative variants (type 2 VWD), because of a dysfunctional VWF. Whereas inheritance is autosomal dominant and bleeding tendency is heterogeneous in type 1 and 2, type 3 patients present moderate-to-severe bleeding diathesis and display a recessive pattern of inheritance.
Although the responsible genetic background has been extensively clarified over the recent years, providing insights on the structure-function relationship of the protein, the cellular basis of the disorder is being investigated for a few mutations only recently. In several cases, increased clearance of the mutant VWF may be responsible for the disease. Standardized criteria for the definition of bleeding history and appropriate history collection are now available, but estimates of bleeding risk are largely lacking.
VWD, the most frequent inherited bleeding disorder, has been the subject of extensive pathophysiological and clinical studies. The novel evidences provide accurate insights on the mechanisms of the disease and the bleeding risk associated with VWF deficiency or abnormality.
血管性血友病（VWD）是一种常染色体遗传性出血性疾病，由血管性血友病因子（VWF）缺乏或异常引起。VWF 是一种主要由内皮细胞产生的多聚体黏附蛋白。VWF 在初级止血中至关重要，因为它促进血小板黏附在血管损伤部位的血管内皮下，在凝血中，VWF 是因子 VIII 的载体。VWD 具有高度异质性，因为导致不同临床和实验室表型的分子机制可能很复杂。VWD 分为 VWF 的定量缺乏（1 型和 3 型 VWD）和定性变异（2 型 VWD），因为 VWF 功能障碍。1 型和 2 型的遗传方式为常染色体显性遗传，出血倾向呈异质性，而 3 型患者表现为中重度出血倾向，并呈隐性遗传模式。
尽管近年来已广泛阐明了相关的遗传背景，为该蛋白的结构-功能关系提供了深入了解，但直到最近才对该疾病的细胞基础进行了一些突变的研究。在某些情况下，突变型 VWF 的清除增加可能是导致疾病的原因。目前已经有用于定义出血史和适当病史采集的标准化标准，但仍缺乏对出血风险的估计。
VWD 是最常见的遗传性出血性疾病，已成为广泛的病理生理学和临床研究的主题。新的证据为该疾病的发病机制和与 VWF 缺乏或异常相关的出血风险提供了准确的见解。
