Lillicrap David
1Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON.
Hematology Am Soc Hematol Educ Program. 2013;2013:254-60. doi: 10.1182/asheducation-2013.1.254.
von Willebrand disease (VWD) is the most common autosomally inherited bleeding disorder. The disease represents a range of quantitative and qualitative pathologies of the adhesive glycoprotein von Willebrand factor (VWF). The pathogenic mechanisms responsible for the type 2 qualitative variants of VWF are now well characterized, with most mutations representing missense substitutions influencing VWF multimer structure and interactions with platelet GPIbα and collagen and with factor VIII. The molecular pathology of type 3 VWD has been similarly well characterized, with an array of different mutation types producing either a null phenotype or the production of VWF that is not secreted. In contrast, the pathogenetic mechanisms responsible for type 1 VWD remain only partially resolved. In the hemostasis laboratory, the measurement of VWF:Ag and VWF:RCo are key components in the diagnostic algorithm for VWD, although the introduction of direct GPIbα-binding assays may become the functional assay of choice. Molecular genetic testing can provide additional benefit, but its utility is currently limited to type 2 and 3 VWD. The treatment of bleeding in VWD involves the use of desmopressin and plasma-derived VWF concentrates and a variety of adjunctive agents. Finally, a new recombinant VWF concentrate has just completed clinical trial evaluation and has demonstrated excellent hemostatic efficacy and safety.
血管性血友病（VWD）是最常见的常染色体遗传性出血性疾病。该疾病表现为一系列与黏附糖蛋白血管性血友病因子（VWF）相关的数量和质量方面的病理变化。目前，VWF 2型定性变异的致病机制已得到充分表征，大多数突变表现为错义替换，影响VWF多聚体结构以及与血小板糖蛋白Ibα、胶原蛋白和凝血因子VIII的相互作用。3型VWD的分子病理学也已得到类似的充分表征，一系列不同的突变类型会产生无效表型或导致VWF无法分泌。相比之下，1型VWD的致病机制仍仅部分得到解决。在止血实验室中，VWF:Ag和VWF:RCo的检测是VWD诊断流程中的关键组成部分，尽管直接GPIbα结合检测方法的引入可能会成为首选的功能检测方法。分子遗传学检测可提供更多帮助，但其应用目前仅限于2型和3型VWD。VWD出血的治疗包括使用去氨加压素、血浆源性VWF浓缩物以及多种辅助药物。最后，一种新型重组VWF浓缩物刚刚完成临床试验评估，已证明具有出色的止血疗效和安全性。
