Comparative Effectiveness in the Diagnosis of VWD

描述(申请人提供)：von Willebrand病是一种常见的出血性疾病，最近因在某些群体(月经过多)被低估而受到科学审查，同时在另一些群体(高达1%-2%的人口)可能被过度诊断。在美国、加拿大、英国和欧盟进行的回顾性研究表明，当VWF水平低于30IU/dL时，VWD的诊断通常是无可争辩的。通常，当1个VWF低于正常范围(&lt；50IU/dL)时，VWD被诊断为VWD。使用30IU/dL的严格水平，在重新研究的548例VWD指标病例中，69%的患者没有降低VWF：Ag或VWF：RCO。这项建议将前瞻性地研究9个参与中心中的一个血液学家转诊的大群人，并在5年的重复研究中研究局部诊断检测与中心检测的相关性。在头两年，这项测试将是盲目的，并将这些结果与未来两年的类似测试进行比较 3年内，这些机构之间将有不盲目的中央测试和积极的质量控制计划。变异型(2型)VWD在15%-20%的VWD患者中被诊断出来。在这项前瞻性研究中，将开发和评估新的筛查试验和新的VWF表型试验。一些定量出血评分(QB)已经被开发出来，有助于区分有VWD和没有VWD的受试者，但它们还没有被用来评估实际的出血风险。两个大的队列，一个成人和一个儿童，将用几个QB进行研究，并将这些分数与他们的出血风险进行前瞻性比较。该项目建议提高诊断VWD所需的保真度、成本效益和灵敏度

DESCRIPTION (provided by applicant): Von Willebrand Disease is a commonly diagnosed bleeding disorder that has recently come under scientific scrutiny for being under diagnosed in some groups (menorrhagia) at the same time it may be over diagnosed in others (up to 1-2% of the population). Retrospective studies have been done in the US, Canada, UK, and EU suggesting that the diagnosis of VWD is usually incontrovertible when levels of VWF are less than 30 IU/dL. Frequently, VWD is diagnosed when 1 VWF test is below the normal range (<50 IU/dL). Using the stringent level of 30 IU/dL, 69% of 548 VWD index cases, on restudy did not have reduced VWF:Ag or VWF:RCo. This proposal will study prospectively a large cohort of individuals referred to hematologists at one of 9 participating Centers and study the correlation of local diagnostic testing to central testing on repetitive study over a 5 year period. For the fist 2 years, this testing will be blinded and these results compared to similar testing over the next 2 3 years when there will be unblinded central testing and active quality control program between these institutions. Variant (type 2) VWD is diagnosed in 15-20% of individuals with VWD. New screening tests and a new VWF-phenotyping test will be developed and evaluated in this prospective study. Several quantitative bleeding scores (QBS) have been developed that help to differentiate subjects with VWD from those without VWD, but they have not been utilized to assess actual bleeding risk. Two large cohorts, one adult and one pediatric, will be studied with several QBS and these scores compared to their risk of hemorrhage prospectively. This project proposes to improve the fidelity, cost effectiveness, and sensitivity needed to diagnose VWD