A Patient Centered Approach to Restarting Oral Anticoagulant Therapy After Major Hemorrhage

描述(申请人提供)：抗凝剂的大出血是一种戏剧性的表现，由于担心引发另一次出血，导致了对重新启动抗凝剂的偏见。在这种片面的风险评估中，经常忽略的是血栓栓塞病的潜在威胁，患者一开始就接受了抗凝治疗。在出血和中风的风险和作为其基础的前瞻性随机数据之间更平衡的方法是迫切需要的。这项建议与NHLBI的使命有关，因为它涉及心脏病，因为口服抗凝最常见的适应症是心房颤动。它处理血液疾病，尽管是由抗凝治疗引起的医源性凝血障碍。它涉及出血的临床环境，包括胃肠道出血和颅内出血。它的目的是通过研究在大出血后重新启动抗凝的风险/好处来提高这些疾病患者的健康。它的目标是立即转化为临床实践。它促进了对 该中心面向新兴科学家和内科医生，并与私人非营利性组织Seton Healthcare Family和位于奥斯汀的新成立的德克萨斯大学戴尔医学院合作，创建并支持强大的协作研究基础设施。在大出血后何时重新开始使用华法林没有循证指南，更不用说越来越多地使用的新型口服抗凝剂(NOAC)了。这项申请的总体目标是阐明一项研究计划，为临床决定在大出血后重新启动抗凝提供信息，这将使米林博士成为该领域的独立有影响力的研究人员。米林博士将在圣安东尼奥的德克萨斯大学健康科学中心注册一个正式的硕士学位项目：临床研究理学硕士。他还将接受止血和凝血、多中心临床试验的设计和实施、适应性试验设计领域的概念培训和卫生经济学方面的广泛和沉浸式培训。米林博士将得到史蒂文·沃拉赫、斯科特·贝里·托德·奥姆斯特德和杰罗尔德·利维博士的精心指导，他们利用正式培训课程和非正式会议框架，汲取他们丰富而多样的经验和指导。米林博士将进行一个分三个阶段的研究设计，包括开发临床试验的国家实践调查工具(对患者、PCP和心脏病专家的调查)，为更大的多中心、适应性的“时间剂量”临床试验和未来的R01提交奠定基础，以找到重新开始的理想时间 在大出血后口服抗凝剂，以平衡复发出血的风险和血栓栓塞病的风险。

DESCRIPTION (provided by applicant): Major hemorrhage on anticoagulants is a dramatic presentation that creates a bias against restarting the anticoagulant for fear of precipitating another hemorrhage. What often gets lost in this one-sided assessment of risk is the underlying threat of thromboembolic disease, for which the patient was anticoagulated to begin with. A more balanced approach between the risk of hemorrhage and stroke and prospective randomized data on which to base it is direly needed. This proposal is relevant to the mission of NHLBI as it deals with heart disease, since the most common indication for oral anticoagulation is atrial fibrillation. It deals with blood disease, albeit an iatrogenic coagulopathy caused by anticoagulation therapy. It deals with the clinical setting of bleeding, both in gastrointestinal bleeding and intracranial hemorrhage. It aims to enhance the health of patients with these diseases by studying the risk/benefit of restarting anticoagulation after major hemorrhage. Its goals are immediately translational into clinical practice. It fosters training and mentoring of an emerging scientist and physician, and it creates and supports a robust, collaborative research infrastructure in partnership with the private non-profit Seton Healthcare Family and the new University of Texas Dell Medical School in Austin. There are no evidence-based guidelines on when to restart warfarin after major hemorrhage, much less the Novel Oral Anticoagulants (NOACs) increasingly being used. The overall goal of this application is to elucidate a research plan to inform the clinical decision to restart anticoagulation after major hemorrhage that will establish Dr. Milling as an independent impactful researcher in this field. Dr. Milling will enrollin a formal master's degree program: Masters of Science in Clinical Investigations at the University of Texas Health Science Center - San Antonio. He will also undergo extensive and immersive training in hemostasis and coagulation, the design and conduct of multicenter clinical trials, conceptual training in the field of adaptive trial design, and health economics. Dr. Milling will receive careful mentorship from Drs. Steven Warach, Scott Berry Todd Olmstead and Jerrold Levy utilizing both formal training curriculum and informal meeting frameworks to draw from their extensive and diverse experience and guidance. Dr. Milling will conduct a three-phased research design, including the development of a National Practice Survey Tool for Clinical Trials (survey of patients, PCPs, and Cardiologists), laying the ground work for a larger multicenter, adaptive, "time dose" clinical trial and a future R01 submission, to find the ideal time to restart oral anticoagulants after a major hemorrhage that balances the risk of recurrent hemorrhage with the risk of thromboembolic disease.