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

项目摘要/摘要 这项建议的主要目标是帮助我进一步发展成为该地区的独立调查员。 围产期止血的转化性和临床研究。以我在母婴科的临床背景 在流行病学和翻译研究方法方面的医学和研究经验，我是理想的位置 通过NIH K23职业指导发展奖励机制取得成功。建议进行的研究 重点是改进方法以识别有产后出血风险的妇女并评估最佳 剂量氨甲环酸(TXA)预防高危妇女。具体目标如下：1) 完善需要输血分娩的统计风险预测模型，2)进行 在分娩时预防性使用TXA的前瞻性临床药代动力学研究，以及3)确定 围产期血栓素A的药效学研究及产前标志物预测 围产期输血。总而言之，这些目标将更好地识别患有严重疾病的风险最高的女性 产后出血及血栓素A的最佳剂量和止血效果 预防出血。我已经在她的研究团队中找到了优秀的导师和合作者/顾问 以帮助实现所概述的目标。该项目的多学科性质证明了更大规模的指导是合理的 为了我的成功，我需要一个团队。主要导师是约翰·范登·安克博士，他是一位国际专家 由美国国立卫生研究院资助的药代动力学研究和翻译研究领域的公认专家。我的三个 其他共同导师包括乔治华盛顿生物统计中心的高级流行病学家马德琳·赖斯博士。 乔治华盛顿医学院协会的高级生物统计师理查德·阿姆杜尔和内奥米·鲁班博士，以及 国际公认的美国国立卫生研究院资助的儿科输血医学专家。对我的成功很重要 目标2的完成是与乔治华盛顿大学产科麻醉师杰弗里·伯杰博士的合作。最后，两个 其他高级调查人员和国际公认的专家是Alisa Wolberg博士和Andra博士 詹姆斯。他们的合作和职业指导将有助于确保我在工作中特别是以后取得成功 这个奖项。我将参加课程作业和重点工作坊，以及旨在 促进调查员独立性。我将受益于一个理想的工作环境，植根于临床和 翻译科学研究所与乔治华盛顿大学和国家儿童医学中心合作，但也延长了 通过在乔治华盛顿生物统计中心的补充培训和沃尔伯格博士的止血和血栓形成 实验室。总之，这项提案提出了重要的、创新的和可行的目标，并将为我提供 有了工具和指导，可以发展成为独立的调查员，更好地了解 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.