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

项目总结/摘要 血友病是一种遗传性凝血因子VIII或IX缺乏症，会导致关节出血和致残 关节病，沿着肌肉出血。静脉注射预防因子药物， 每周出血次数减少，但不能消除出血。消除突破性出血的最大努力 预防改变药物治疗方案，以增加因子水平;然而，这通常不成功， 增加了经济负担和/或更频繁的注射。努力消除突破性出血 由于对出血生物力学的不完全理解而受到限制。这种知识差距也限制了 选择安全有效的体力活动，这对血友病（PwH）患者预防 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， 客观测量PwH中与下肢关节和肌肉出血相关的力， 降低出血风险的长期目标。这一长期目标将在未来的研究中实现， 将收集数据，以建立出血风险的时间依赖性统计模型，包括止血、关节脆弱性， 和生物力学出血风险成分。本研究的目的是确定过去 关节出血影响下肢关节负荷的不对称性，在运动实验室中使用运动测量 捕获和测力板技术（目标1）;确定运动实验室不对称性对未来低 肢体关节和肌肉出血（目标2）;以及开发工具，在运动实验室外收集运动数据 使用惯性测量单元（伊穆斯）（目标3）。 K23奖候选人Beth Warren博士的近期目标是为她增加新技能 生物工程和血液学背景。其中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;血友病关节的测量结果和意义; 并为今后的研究规划了统计模型。实现这些目标将支持她的长期职业目标， 成为血友病关节结局和活动相关出血风险方面的领先专家。 沃伦博士将在她的导师玛丽莲博士的支持下完成她的研究和培训目标 Manco-Johnson（血友病临床研究）和James Alberlo博士（生物力学，运动分析）。的 科罗拉多大学血友病和血栓中心（UC-HTC）将提供世界一流的基础设施， 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的丰富经验和专业知识。科罗拉多大学提供初级 教师有许多机会，以促进过渡到研究职业独立。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， 出血生物力学，同时也获得必要的经验和培训，开始她的职业生涯， 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.