What have we learned from large population studies of von Willebrand disease?
What have we learned from large population studies of von Willebrand disease?
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DOI：
10.1182/asheducation-2016.1.670
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发表时间：
2016-12-01
影响因子：
3
通讯作者：
Flood, Veronica H.
中科院分区：
文献类型：
--
作者：
Montgomery, Robert R.;Flood, Veronica H.
血管性血友病因子（VWF）是止血过程（包括胶原结合、血小板粘附和血小板聚集）的关键调节因子。它还作为载体蛋白，使血浆因子VIII合成、释放和存活正常化。虽然通过免疫测定法测量VWF蛋白在不同机构之间具有合理的可比性，但VWF瑞斯托康辅因子活性（VWF：RCo）的测量具有显著的变异性。VWF功能的其他测试，包括胶原蛋白结合或血小板糖蛋白IIb-IIIa结合，并不是普遍可用的，但这些功能缺陷可能会导致大出血，即使与正常的VWF抗原（VWF：Ag）和VWF：RCo测定。这导致VWD的过度诊断和诊断不足。新的VWF功能检测方法（使用重组糖蛋白Ib而不是整个血小板）已经开发出来，可以改善实验室间的变异性。其中一些测试并不是统一可用的，可能在美国没有许可证。目前尚无关于血管性血友病（VWD）患者VWF的大型纵向研究。患者有时被诊断与一个单一的诊断VWF面板。血浆VWF水平随年龄增加而增加，但尚不清楚这是否会导致出血减少，或者是否应使用不同的正常范围来识别年龄相关的VWF降低。为了定量比较VWD患者和正常人的出血症状，最近在欧盟、加拿大、英国、荷兰和美国的研究使用了半定量出血评估工具（BAT）。即使有仔细的集中检测，包括VWF的功能测定，增加BAT也不能解决VWD诊断的所有问题。无论VWD的诊断界限在哪里，VWF仍然是一个连续变量。因此，VWD可能是一种需要频繁治疗的严重出血性疾病，也可能是一种可能与临床无关的轻度疾病。正如Goodeve博士在她的演讲中所讨论的那样，遗传学帮助我们诊断VWD的2型功能变体，但对于许多处于正常和低VWF界面并可能诊断为1型VWD的患者没有帮助。血液学家对VWF水平降低的患者的管理仍然需要临床医学的艺术和科学。
Von Willebrand factor (VWF) is a critical regulator of hemostatic processes, including collagen binding, platelet adhesion, and platelet aggregation. It also serves as a carrier protein to normalize plasma factor VIII synthesis, release, and survival. While VWF protein measurements by immunoassay are reasonably comparable between institutions, the measurement of VWF ristocetin cofactor activity (VWF:RCo) has significant variability. Other tests of VWF function, including collagen binding or platelet glycoprotein IIb-IIIa binding, are not universally available, yet these functional defects may cause major bleeding even with normal VWF antigen (VWF:Ag) and VWF: RCo assays. This results in both the overdiagnosis and underdiagnosis of VWD. Newer assays of VWF function (using recombinant glycoprotein Ib rather than whole platelets) have been developed that may improve interlaboratory variability. Some of these tests are not uniformly available and may not be licensed in the United States. Large longitudinal studies of VWF in von Willebrand disease (VWD) patients are not available. Patients are sometimes diagnosed with a single diagnostic VWF panel. Plasma VWF levels increase with age, but it is not clear if this results in less bleeding or whether different normal ranges should be used to identify age-related decreases in VWF. In order to quantitatively compare bleeding symptoms in VWD patients and normal individuals, recent studies in the European Union, Canada, United Kingdom, Holland, and the United States have used semiquantitative bleeding assessment tools (BATs). Even with careful centralized testing, including functional assays of VWF, addition of a BAT does not solve all of the problems with VWD diagnosis. No matter where the line is drawn for diagnosis of VWD, VWF is still a continuous variable. Thus, VWD can be a severe hemorrhagic disease requiring frequent treatment or a mild condition that may not be clinically relevant. As will be discussed by Dr. Goodeve in her presentation, genetics has helped us to diagnose type 2 functional variants of VWD but has not been helpful for the many patients who are at the interface of normal and low VWF and carry the possible diagnosis of type 1 VWD. The hematologist's management of patients with reduced levels of VWF still requires both the art and science of clinical medicine.