Developing Primary Care Algorithms for Early Identification of Young Women with von Willebrand Disease

项目总结/摘要 女性出血性疾病仍然认识不足，治疗不足。虽然专家指南 建议筛查大量月经出血（HMB）的青少年血管性血友病（VWD）， 我们的团队已经确定，筛选不足仍然很普遍。VWD筛查的最新进展包括 出血评估工具（BAT）的验证，与国际血栓学会和 止血BAT（ISTH-BAT）作为当前标准。然而，ISTH-BAT的参考范围 年轻女性的得分是未知的，也缺乏研究检查BAT的准确性，在小学 护理设置。我们的团队还表明，缺铁在患有HMB的年轻女性中很常见， 护理点（POC）铁蛋白技术是新近可用的，其作为VWD的筛查工具， HMB尚未进行评价。此R 01应用程序的主要目标是比较三种方法的有效性 筛查策略，以识别具有VWD基础诊断的HMB年轻女性：1）BAT，2） POC铁蛋白和3）组合的BAT + POC铁蛋白。我们进行这项研究的基本原理是早期诊断VWD 可以通过使卫生保健提供者能够最佳地管理 HMB，并为未来的手术事件和分娩制定护理计划，从而降低发病率和严重程度 出血事件。凭借我们在BAT、VWD和过去成功招募年轻人方面的专业知识， 为了促进妇女参与HMB研究，我们将通过以下具体目标实现我们的目标：1）建立 10-20岁月经后女性的一般人群中ISTH-BAT的参考范围，2） 比较以下筛查工具（BAT、铁蛋白、BAT+铁蛋白）在识别年轻女性中的有效性， HMB和基础VWD，以及3）评估初级保健VWD筛查算法的可行性，以及 患者、护理人员和临床医生的经验。我们的研究人群将包括约1，800名绝经后女性 在五个初级保健诊所接受治疗。参与者将在他们的研究期间完成BAT和POC铁蛋白。 临床访视符合HMB研究定义的受试者将接受VWD实验室检测。我们将收集 可行性测量（即，参与率、完成筛选算法的时间）。我们将进行半- 与参与者、父母和医疗保健提供者的一部分进行结构化访谈，以探索以下领域， VWD筛查对诊所工作流程的可接受性、适当性和影响。我们的核心假设 BAT +铁蛋白比单独的BAT或POC铁蛋白对VWD具有更高的特异性。我们的项目是创新的 因为它改变了对患有出血性疾病的年轻女性的研究， 中心的初级保健机构，其中年轻妇女与HMB最初存在。建议的研究 这里将作为比较VWD初级保健筛查算法与标准护理的基础 在一项前瞻性临床试验中，以测量其对健康结果的影响，例如开始HMB和缺铁 治疗、专科转诊、基础出血性疾病的实验室筛查和患者生活质量。

PROJECT SUMMARY / ABSTRACT Bleeding disorders in women remain under-recognized and under-treated. Although expert guidelines recommend screening adolescents with heavy menstrual bleeding (HMB) for von Willebrand Disease (VWD), our team has identified that under-screening remains widespread. Recent advances in VWD screening include the validation of bleeding assessment tools (BATs), with the International Society of Thrombosis and Haemostasis BAT (ISTH-BAT) serving as the current standard. However, the reference range of the ISTH-BAT score for young women is unknown, and there is a lack of research examining the accuracy of BATs in primary care settings. Our team has also shown that iron deficiency is common in young women with HMB, and while point-of-care (POC) ferritin technology is newly available, its utility as a screening tool for VWD in women with HMB has not been evaluated. The primary objective of this R01 application is to compare the validity of three screening strategies to identify young women with HMB who have an underlying diagnosis of VWD: 1) BAT, 2) POC ferritin, and 3) combined BAT + POC ferritin. Our rationale for this research is that early diagnosis of VWD in women with HMB can alleviate morbidity and mortality by enabling health care providers to optimally manage HMB and develop care plans for future surgical events and childbirth, thus decreasing the incidence and severity of bleeding events. Building upon our expertise in BATs, VWD, and past success in the recruitment of young women for HMB studies, we will achieve our objectives through the following specific aims: 1) establish the reference range of the ISTH-BAT in a general population of post-menarchal females 10-20 years of age, 2) compare the validity of the following screening tools (BAT, ferritin, BAT+ferritin) in identifying young women with HMB and underlying VWD, and 3) assess the feasibility of a primary care VWD screening algorithm, as well as patient, caregiver, and clinician experience. Our study population will include ~1,800 post-menarchal females presenting for care at five primary care clinics. Participants will complete the BAT and POC ferritin during their clinical visit. Those meeting the study definition of HMB will undergo laboratory testing for VWD. We will collect feasibility measurements (i.e., participation rate, time to complete screening algorithm). We will perform semi- structured interviews with a subset of participants, parents, and health care providers to explore domains such as the acceptability, appropriateness, and impact of VWD screening on clinic workflows. Our central hypothesis is that BAT + ferritin will have higher specificity for VWD than BAT or POC ferritin alone. Our project is innovative because it shifts the study of young women with bleeding disorders from the status quo of specialized hematology centers to the primary care settings in which young women with HMB initially present. The studies proposed here will serve as a foundation for comparing a VWD primary care screening algorithm against standard of care in a prospective clinical trial to measure its effect on health outcomes such as initiation of HMB and iron deficiency treatment, specialty referral, laboratory screening for underlying bleeding disorders, and patient quality of life.