Reduced von Willebrand factor survival in von Willebrand disease: pathophysiologic and clinical relevance
Reduced von Willebrand factor survival in von Willebrand disease: pathophysiologic and clinical relevance
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DOI：
10.1111/j.1538-7836.2009.03381.x
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发表时间：
2009-07-01
影响因子：
10.4
通讯作者：
Rodeghiero, F.
中科院分区：
文献类型：
--
作者：
Castaman, G.;Tosetto, A.;Rodeghiero, F.
血管性血友病（VWD）的特点是广泛的异质性的临床和实验室表型。通过去氨加压素释放的血管性血友病因子（VWF）的高度可变去除率进一步增加了表型的复杂性，这与输注后峰值水平无关。在初步证明R1205H突变（VWD Vicenza）患者中存在VWF存活率降低后，其他几种突变（主要发生在VWF D3结构域）已显示与释放的VWF加速清除相关。O型血的正常受试者显示去氨加压素后生存率降低，强调了ABO血型中存在的不同VWF糖基化的作用。最近的证据表明，肝脏和脾脏巨噬细胞负责通过摄取和细胞内降解VWF清除，但仍然不知道为什么一些VWF突变体更容易增加清除。
Von Willebrand disease (VWD) is characterized by a wide heterogeneity of clinical and laboratory phenotypes. The complexity of the phenotype is further increased by a highly variable removal rate of von Willebrand factor (VWF) released by desmopressin, which is independent of post-infusion peak level. After the initial demonstration that a reduced VWF survival is present in patients with R1205H mutation (VWD Vicenza), several other mutations, mostly occurring in the VWF D3 domain, have been shown to be associated with accelerated removal of released VWF. Normal subjects with O blood group show reduced survival after desmopressin, underlining the role of different VWF glycosylation present in ABO blood group. Recent evidence suggests that liver and spleen macrophages are responsible for VWF clearance through uptake and endocellular degradation, but it is still not known why some VWF mutants are more prone to increased clearance.