Molecular Impact of VWF on Clinical VWD

VWF 对临床 VWD 的分子影响

• 批准号: 8608577
• 负责人: ROBERT R MONTGOMERY
• 金额: $ 29.57万
• 依托单位: VERSITI WISCONSIN, INC.
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8608577
• 关键词: Abbreviations; Abnormal Laboratory Test Result; Address; Adult; Affect; African American; Antibiotics; Asian Americans; Binding; Biological Assay; Biology; Blood Platelets; Categories; Clinical; Data; Diagnosis; Diagnostic; Disease; Dose; Enrollment; Enzyme-Linked Immunosorbent Assay; Ethnic Origin; European Union; Evaluation; Family; Female; Funding; Gene-Modified; Genetic Polymorphism; Genotype; Guidelines; Hemophilia A; Hemorrhage; Hispanic Americans; In Vitro; Indiana; Individual; Label; Laboratories; Menorrhagia; Molecular; Mutation; National Heart, Lung, and Blood Institute; New York; Pathway interactions; Patients; Pattern; Phenotype; Pilot Projects; Population; Population Study; Public Health; Quality of life; Race; Reagent; Recording of previous events; Recruitment Activity; Research; Research Design; Risk; Ristocetin; Scientist; Sensitivity and Specificity; Symptoms; System; Test Result; Testing; Thrombocytopenia; Time; United States; United States National Institutes of Health; Variant; Woman; Women' s Health; base; clinical phenotype; clinically relevant; cohort; comparative; improved; in vivo; indexing; meetings; programs; time use; treatment center; von Willebrand Disease

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.

冯·维勒布兰德病在美国是一种常见的诊断。在某些情况下，这种疾病的诊断不足， 尤其是患有月经过多的成年女性。在其他情况下，VWD 可能会被过度诊断 诊断时的实验室检测不太精确，诊断时实验室结果的解释不正确， 实验室检测异常，但患者没有临床出血相关性，或者“领域”发生了变化 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）研究，以阐明 VWD 诊断的严格性并提供 建议的证实、质疑或消除 VWD 诊断的方法。目标2将发展 改进了 VWF 功能的替代测定。目前唯一广泛使用的 VWF 功能测试是 瑞斯托菌素辅助因子测定 (VWF:RCo)。敏感性、特异性和特异性方面存在广泛公认的问题 该测定的临床相关性 - 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 基于美国人口中的种族或民族的序列变异。目标4将开展临床项目 目前正在单个中心进行试点（密尔沃基的月经过多和印第安纳州的生活质量研究）。 该研究人群不仅对目标 1 中提出的研究很重要，而且对于 项目 2 和项目 3 中提出的研究。这个仔细的临床和实验室表型分析 该项目不仅将提高 VWD 诊断的保真度，还将开始探索如何处理 VWD 的途径 先前诊断出 VWD 的个体可能既没有异常的实验室检测，也没有当前的检测结果 异常临床出血风险。