Exploring the Biomechanics of Joint Bleeding in Persons with Hemophilia to Better

项目摘要/摘要 血友病是一种遗传性凝血因子或IX的缺陷，会导致关节出血和残疾 关节病，并伴有肌肉出血。预防因子静脉给药几次 每周出血次数减少，但并不能消除出血。最大的努力是消除突破性出血 预防改变药物治疗方案以提高因子水平；然而，这通常不成功，而且 随着财政负担的增加和/或更频繁的注射。努力消除突破性出血 受限于对出血生物力学的不完全理解。这种知识差距也制约了 选择安全有效的体力活动，这对血友病患者(PwH)预防很重要 肥胖，改善社会功能，减少心理健康问题。这项研究开发了一些方法来 客观测量PwH中与下肢关节和肌肉出血相关的力量，以满足 降低出血风险的长期目标。这一长期目标将在未来的一项研究中实现 将收集数据以建立出血风险的随时间变化的统计模型，其中包括止血、关节脆弱性、 和生物力学出血风险组件。当前研究的目标是确定过去 关节出血影响在运动实验室中使用运动测量的下肢关节负荷的不对称性 捕捉和力板技术(目标1)；确定运动实验室不对称性对未来Low的影响 四肢关节和肌肉出血(目标2)；并开发工具以在运动实验室之外收集运动数据 使用惯性测量单元(IMU)(目标3)。 这个K23奖项的候选人贝丝·沃伦博士的直接目标是为她增加新的技能 生物工程和血液学背景。这些技术包括内部和外部的运动测量技术 运动实验室，包括信号处理技术；血友病联合结果测量和意义； 以及未来研究的统计模型规划。实现这些目标将支持她的长期职业目标 成为血友病联合结局和活动相关出血风险方面的领先专家。 Warren博士将在她的导师Marilyn博士的支持下实现她的研究和培训目标 Manco-Johnson(血友病临床研究)和James Carollo博士(生物力学、运动分析)。这个 科罗拉多大学血友病和血栓形成中心(UC-HTC)将为 支持沃伦博士的职业发展和研究目标，包括设施和研究人员 在血友病临床研究方面有丰富的经验和专业知识。科罗拉多大学为青少年提供 教职员工有许多机会促进向研究职业独立的过渡。通过 完成她的研究和培训目标，沃伦博士将推进客观测量的科学 流血的生物力学，同时也获得了开始她职业生涯所需的经验和培训 独立调查员。

PROJECT SUMMARY/ABSTRACT Hemophilia is an inherited deficiency of clotting factor VIII or IX, which causes joint bleeding and crippling arthropathy, along with muscle bleeding. Prophylactic factor medication administered intravenously several times per week decreases but does not eliminate bleeding. Most efforts to eliminate breakthrough bleeding on prophylaxis alter medication regimens to increase factor levels; however, this is often not successful and comes with increased financial burden and/or more frequent injections. The effort to eliminate breakthrough bleeding is limited by an incomplete understanding of bleeding biomechanics. This knowledge gap also constrains choices for safe and effective physical activity, which is important in persons with hemophilia (PwH) to prevent obesity, improve social functioning, and decrease mental health concerns. This study develops methods to objectively measure forces related to lower extremity joint and muscle bleeding in PwH, in order to fulfill the long-term goal of decreasing bleeding risk. This long-term goal will be accomplished in a future study that will collect data to build a time-dependent statistical model of bleeding risk that includes hemostatic, joint fragility, and biomechanical bleeding risk components. The objectives of the current study are to determine how past joint bleeding influences asymmetry in lower extremity joint loading, measured in a Motion Lab using motion capture and force plate technology (aim 1); to determine the influence of motion lab asymmetry on future lower extremity joint and muscle bleeding (aim 2); and to develop tools to collect motion data outside the Motion Lab using inertial measurement units (IMUs) (aim 3). The immediate goals of the candidate for this K23 award, Dr. Beth Warren, are to add new skills to her bioengineering and hematology background. These include motion measurement techniques inside and outside the Motion Lab, including signal processing techniques; hemophilia joint outcome measurement and meaning; and statistical model planning for future studies. Achieving these goals will support her long-term career goal to become a leading expert in hemophilia joint outcomes and activity-associated bleeding risk. Dr. Warren will accomplish her research and training aims with the support of her mentors, Dr. Marilyn Manco-Johnson (hemophilia clinical research) and Dr. James Carollo (biomechanics, movement analysis). The University of Colorado Hemophilia and Thrombosis Center (UC-HTC) will provide world-class infrastructure to support Dr. Warren’s career development and research objectives, including facilities and research staff with extensive experience and expertise in hemophilia clinical research. The University of Colorado provides junior faculty members with numerous opportunities to facilitate the transition to research career independence. By completing her research and training aims, Dr. Warren will advance the science of objective measurement of bleeding biomechanics, while also obtaining experience and training necessary to begin her career as an independent investigator.