Molecular Impact of VWF on Clinical VWD

冯·威尔布兰德病在美国是一种常见的诊断。在某些情况下，这种疾病被低估了， 尤其是有月经过多的成年女性。在其他情况下，VWD可能被过度诊断 诊断时实验室检测不准确，诊断时对实验室结果的错误解释， 实验室检查异常，但患者没有临床出血相关，或者“视野”发生了变化 关于诊断标准(NHLBI指南)的严格性。该项目的目标1将继续 正在进行的1型(和其他VWD类型)研究，以澄清VWD诊断的严格性并提供 关于证实、质疑或排除VWD诊断的建议方法。目标2将会发展 改进了VWF功能的替代分析。目前唯一被广泛使用的VWF函数测试是 瑞斯托菌素协同因子分析(VWF：RCO)。人们普遍认识到的问题包括敏感性、特异性和 该检测的临床相关性-部分与瑞斯托菌素和测试VWF之间的相互作用有关。目标3 将继续通过确定VWF来确定VWF改变的基因型-表型相关性 美国人口中基于种族或民族的序列差异。AIM 4将开展临床项目 目前正在单一中心进行试点(密尔沃基的月经过多和印第安纳州的生活质量研究)。 这一研究群体不仅对目标1中提出的研究很重要，而且对 项目2和项目3中提出的研究。在这个项目中，仔细的临床和实验室表型 该项目不仅将提高VWD诊断的保真度，而且将开始如何接近 既往诊断为VWD的个人，可能既没有实验室检查异常，也没有目前的 异常的临床出血风险。

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.