Favaloro Emmanuel J
Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), Pathology West, Westmead Hospital, Westmead, New South Wales, Australia.
Semin Thromb Hemost. 2014 Jul;40(5):551-70. doi: 10.1055/s-0034-1383546. Epub 2014 Jun 30.
von Willebrand disease (VWD) is a disorder characterized by deficiency of, or defects in, von Willebrand factor (VWF). VWD was originally identified by Erik Adolf von Willebrand, who in early 1924 investigated a large family suffering from a bleeding disorder that seemed to differ from hemophilia. Erik von Willebrand undertook some initial laboratory investigations to conclude the involvement of a plasma factor, the lack of which prolonged the bleeding time, but failed to impair coagulation times and clot retraction. By the end of the 1960s, VWD was accepted as a combined deficiency of factor VIII (FVIII) and another plasma factor responsible for normal platelet adhesion. Just how these two functions were related to each other was less clear and the diagnostic tests available at the time were poorly reproducible, cumbersome, and unreliable; thus, VWD was poorly delineated from other coagulation and platelet disorders. The early 1970s saw a revolution in diagnostics when ristocetin was identified to induce platelet aggregation, and this formed the basis of the first consistent and reliable VWF "activity" test, permitting quantification of the platelet adhesive function missing in VWD. Concurrently, immunoprecipitating techniques specific for VWF were defined, and the application of such technologies permitted a clearer understanding of both VWF and VWD heterogeneity. Continued exploration of the structure and function of VWF contributed greatly to the understanding of platelet physiology, ligand receptor interaction and pathways of cellular interaction and activation. Recently, additional assays evaluating other functions of VWF, including collagen binding, platelet glycoprotein Ib binding, and FVIII binding, have improved the diagnosis of VWD. The purpose of this narrative review is to explore the history of phenotypic VWD diagnostics, with a focus on laboratory milestones from the past as well highlighting recent and ongoing innovations, and ongoing challenges and possible solutions.
血管性血友病（VWD）是一种以血管性血友病因子（VWF）缺乏或缺陷为特征的疾病。VWD最初由埃里克·阿道夫·冯·维勒布兰德发现，他在1924年初对一个患有出血性疾病的大家族进行了调查，这种疾病似乎与血友病不同。埃里克·冯·维勒布兰德进行了一些初步的实验室研究，得出结论认为有一种血浆因子参与其中，缺乏该因子会延长出血时间，但不会影响凝血时间和血块回缩。到20世纪60年代末，VWD被认为是因子VIII（FVIII）和另一种负责正常血小板黏附的血浆因子联合缺乏。这两种功能之间究竟如何相互关联尚不清楚，而且当时可用的诊断测试重复性差、操作繁琐且不可靠；因此，VWD与其他凝血和血小板疾病难以区分。20世纪70年代初，当瑞斯托霉素被发现可诱导血小板聚集时，诊断领域发生了一场革命，这构成了首个一致且可靠的VWF“活性”测试的基础，从而能够对VWD中缺失的血小板黏附功能进行定量。同时，定义了针对VWF的免疫沉淀技术，这些技术的应用使人们对VWF和VWD的异质性有了更清晰的认识。对VWF结构和功能的持续探索极大地促进了对血小板生理学、配体受体相互作用以及细胞相互作用和激活途径的理解。最近，评估VWF其他功能的额外检测方法，包括胶原结合、血小板糖蛋白Ib结合和FVIII结合，改善了VWD的诊断。本叙述性综述的目的是探讨VWD表型诊断的历史，重点关注过去的实验室里程碑以及近期和正在进行的创新，以及持续存在的挑战和可能的解决方案。
