Comparative Effectiveness in the Diagnosis of VWD

描述（由申请人提供）：血管性血友病是一种常见的出血性疾病，最近受到科学审查，因为在某些人群中诊断不足（月经过多），同时在其他人群中可能被过度诊断（高达1-2%的人群）。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30 IU/dL时，VWD的诊断通常是无可争议的。通常，当VWF测试低于正常范围（<50 IU/dL）时，VWD被诊断。使用30 IU/dL的严格水平，548例VWD指数病例中有69%在重新研究时没有VWF：Ag或VWF：RCo降低。本提案将前瞻性研究9个参与中心之一的血液学家转诊的大型个体队列，并研究5年内重复研究中当地诊断检测与中心检测的相关性。在前2年，该试验将设盲，并将这些结果与未来2年的类似试验进行比较 3年，届时这些机构之间将进行非盲中心检测和主动质量控制项目。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，将开发和评价新的筛查试验和新的VWF表型分型试验。已经开发了几种定量出血评分（QBS），有助于区分VWD受试者和无VWD受试者，但尚未用于评估实际出血风险。将采用多个QBS研究两个大型队列（一个成人队列和一个儿童队列），并将这些评分与其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