Prevention of postpartum hemorrhage: identifying pregnant women at risk and determining the safe and effective use of tranexamic acid using state-of-the-art pharmacokinetic/pharmacodynamics modeling

项目总结/摘要 这个建议的主要目标是帮助我进一步发展成为该领域的独立调查员 转化和临床围产期止血研究。以我在母婴方面的临床背景 医学和流行病学和转化研究方法的研究经验，我是理想的定位 通过NIH K23职业指导发展奖机制取得成功。拟定研究 重点是改进方法，以确定妇女在产后出血的风险，并评估最佳的 氨甲环酸（TXA）的剂量用于预防高危妇女。具体目标如下：（1） 改进需要输血的分娩的统计风险预测模型，2）进行 在分娩时使用TXA进行前瞻性临床药代动力学研究，以及3）确定 TXA在围产期的药效学（PD），并探索产前标志物，以预测 围产期输血总的来说，这些目标将更好地确定妇女在最大的风险， 产后出血，并确定最佳剂量和止血效果时， 防止出血。我在她的研究团队中找到了优秀的导师和合作者/顾问 帮助实现既定目标。该项目的多学科性质证明有必要扩大指导范围 团队，让我成功。主要导师是约翰货车登安克博士，一个国际 他是药代动力学研究和转化研究领域公认的专家，并得到NIH的充分资助。我的三 其他共同导师包括马德琳赖斯博士，在GW生物统计中心的高级流行病学家，博士。 理查德·阿姆杜尔是GW医学学院协会的高级生物统计学家，纳奥米·鲁班博士是一名 国际公认的和NIH资助的儿科输血医学专家。对我的成功很重要 目标2的完成是与GW产科麻醉师Jeffrey Berger博士合作。最后，两个 其他高级研究员和国际公认的专家是Alisa Wolberg博士和Andra博士 James.他们的合作和职业指导将有助于确保我在工作中取得成功，尤其是在工作结束后 这个奖。我将参加课程作业和重点研讨会以及旨在 促进调查员的独立性。我将受益于一个理想的工作环境，植根于临床和 转化科学研究所与GW和儿童国家医疗中心合作， 通过GW生物统计中心的补充培训和Wolberg博士的止血和血栓形成 实验室总之，这一建议提出了重要、创新和可行的目标，将为我提供 有了工具和指导，发展成为一个独立的调查员，以更好地了解如何 使用氨甲环酸可以优化围产期止血。

Project Summary/Abstract The primary goal of this proposal is to help further my development into an independent investigator in the area translational and clinical peripartum hemostasis research. With my clinical background in Maternal-Fetal Medicine and research experiences in epidemiologic and translational study methods, I am ideally positioned to succeed through the NIH K23 Career Mentored Development Award mechanism. The proposed study focuses on improving methods to identify women at risk for postpartum hemorrhage and evaluate the optimal dosing of tranexamic acid (TXA) for prevention in at risk women. The specific aims are as follows: 1) To improve the statistical risk prediction model for deliveries requiring blood transfusion, 2) To conduct a prospective clinical pharmacokinetic study using TXA prophylactically at time of delivery, and 3) To determine the pharmacodynamics (PD) of TXA in peripartum period and explore pre-delivery markers to predict peripartum blood transfusion. Collectively, these aims will better identify women at greatest risk for severe postpartum hemorrhage and determine the optimal dosing and effects of TXA on hemostasis when used for prevention of hemorrhage. I have identified excellent mentors and collaborators/advisors on her research team to help accomplish the outlined aims. The multidisciplinary nature of the project justifies a larger mentorship team in order for me to be successful. The primary mentor is Dr. John van den Anker, an internationally recognized expert in pharmacokinetic research and translational studies who is well-funded by NIH. My three other co-mentors include Dr. Madeline Rice, a senior epidemiologist at the GW Biostatistics Center, Dr. Richard Amdur, a senior biostatistician at GW Medical Faculty Associates and Dr. Naomi Luban, an internationally recognized and NIH-funded pediatric transfusion medicine expert. Important to my successful completion of Aim 2 is collaboration with GW obstetric anesthesiologist Dr. Jeffrey Berger. Finally, two additional senior investigators and internationally recognized experts are Dr. Alisa Wolberg and Dr. Andra James. Their collaboration and career mentorship will help ensure my success during and especially beyond this award. I will participate in coursework and focused workshops as well as hands-on training designed to promote investigator independence. I will benefit from an ideal working environment, rooted in the Clinical and Translational Science Institute partnering GW and Children’s National Medical Center but also extended through supplemental training at the GW Biostatistics Center and Dr. Wolberg’s hemostasis and thrombosis lab. In summary, this proposal sets forth aims that are significant, innovative and feasible, and will provide me with the tools and mentorship to develop into an independent investigator working to better understand how peripartum hemostasis can be optimized using tranexamic acid.