Molecular Impact of VWF on Clinical VWD

Von Willebrand病在美国是一种常见的诊断。在某些情况下，这种疾病诊断不足， 特别是在月经过多的成年女性中。在其他情况下，VWD可能被过度诊断， 诊断时不太精确的实验室检测，诊断时对实验室结果的错误解释， 实验室检查异常，但患者无临床出血相关性，或“字段”发生变化 关于诊断标准的严格性（NHLBI指南）。该项目的目标1将继续 正在进行的1型（和其他VWD类型）的研究，以澄清VWD诊断的严格性，并提供一个 建议的方法来证实，质疑，或删除VWD的诊断。Aim 2将开发 VWF功能的改进的替代测定。目前唯一广泛使用的VWF功能测试是 维生素C辅因子测定（VWF：RCo）。存在广泛认识到的灵敏度、特异性和 该测定临床相关性部分与利托那韦和受试VWF之间的相互作用有关。目标3 将继续通过测定VWF，确定VWF改变的基因型-表型相关性。 美国人群中基于人种或种族的序列变异。目标4将开展临床项目 目前正在单中心试点（密尔沃基的月经过多和印第安纳州的QOL研究）。 该研究人群不仅对目标1中提出的研究很重要，而且对以下研究也很关键： 项目2和项目3中提出的研究。这种仔细的临床和实验室表型在这方面 该项目不仅将提高VWD诊断的准确性，而且将开始如何接近 先前诊断为VWD的个体可能既没有异常的实验室检测，也没有当前的 异常临床出血风险。

Von Willebrand disease is a common diagnosis in the USA. In some cases the disorder is under-diagnosed, particularly in adult females with menorrhagia. In other situations, VWD may be over-diagnosed based on less precise laboratory testing at the time of diagnosis, incorrect interpretation of the lab results at diagnosis, the lab testing was abnormal but the patient had no clinical bleeding correlate, or the "field" has changed concerning the stringency of diagnostic criteria (NHLBI Guidelines). Aim 1 of this project will continue the ongoing study of type 1 (and other VWD types) to clarify the stringency of VWD diagnosis and provide a suggested approach to substantiating, questioning, or removing the diagnosis of VWD. Aim 2 will develop improved alternative assays for VWF function. Currently the only widely utilized test of VWF function is the ristocetin co-factor assay (VWF:RCo). There are widely recognized problems with sensitivity, specificity, and clinical correlation of that assay - in part do to the interaction between ristocetin and the test VWF. Aim 3 will continue to determine the genotype - phenotype correlation of VWF alteration by determining VWF sequence variations based on race or ethnicity within the US population. Aim 4 will carry out clinical projects that are currently being piloted at single centers (menorrhagia at Milwaukee and QOL Studies at Indiana). Not only is this study population important to the studies proposed in Aim 1, but this cohort is also critical to the studies proposed in Project 2 and Project 3. This careful clinical and laboratory phenotyping in this project will not only improve the fidelity of VWD diagnosis, but it will begin the pathway of how to approach individuals with a prior diagnosis of VWD that might have neither abnormal laboratory testing nor a current abnormal clinical bleeding risk.