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.
Joint bleeding in hemophilia leads to arthropathy and is not fully prevented by standard prophylactic treatments. Joint and muscle bleeding likely cause changes in movement strategies and lower limb biomechanics, which we hypothesize leads to subsequent increased risk of lower extremity bleeding. This proposal seeks to better understand the biomechanics of joint and muscle bleeding, with a goal of quantifying bleeding risk at any given time in future studies.
