Rare bleeding disorders are a group of inherited conditions caused by a deficiency of blood coagulation factors. Due to the low prevalence of these conditions in the general population, there is a scarcity of data to make informed, evidence-based clinical decisions. In this population who are highly susceptible to excessive bleeding, surgeries and invasive procedures pose an additional level of risk for bleeding-related and non-bleeding-related complications, especially in the perioperative period. The data scarcity in patients with rare bleeding disorders is further compounded by an infrequent rate of invasive procedures, sometimes attributed to the hemostatic challenges faced by such interventions among other factors. To address the problem of insufficient data for healthcare decision-making, as well as the assessment of perioperative outcomes in this population, this thesis explores the use of routinely collected data for the creation of a novel surgical database used for the assessment of perioperative hemostasis, complications, and initial surgical plan deviations in patients with rare bleeding disorders. Across five chapters, this thesis provides the methodology for the creation of the Indiana Hemostasis and Thrombosis Center (IHTC) Surgical Database, a descriptive analysis of the population and procedures, and assessment of perioperative outcomes. Approaches to ensure the validity of study results including confounder adjustment by variable selection methods, data quality improvement, missing data description, and imputation methods, were explored. Evidence from randomized controlled was also reviewed using Cochrane methodology to summarize the efficacy of clotting factor concentrates for the prevention of bleeds and bleeding-related complications in patients with hemophilia. Based on findings from the different approaches (observational study designs, randomized controlled trials, and systematic review methodology), recommendations were made regarding methodological and analytical considerations required to ensure valid and reliable perioperative outcome assessment in patients with rare bleeding disorders. The following provides a brief outline of each chapter. Chapter 1 is an introduction that outlines each of the studies in this thesis. Chapter 2 is a descriptive overview of the design, structure, and exploratory analysis of data captured in the IHTC-Surgical Database over a 21-year period. Chapter 3 is a retrospective cohort study that assessed the association between inhibitor status and perioperative hemostasis, complications, and initial surgical plan deviations in patients with hemophilia A and B. Chapter 4 is a systematic review that examined the efficacy of clotting factor concentrates for the prevention of bleeds and bleeding-related complications in patients with hemophilia. Chapter 5 outlines key findings, limitations, implications of the research in this thesis, and methodological considerations for the assessment of perioperative outcomes in patients with bleeding disorders. / Thesis / Doctor of Philosophy (PhD)

京都大学 / 新制・論文博士 / 博士(医学) / 乙第13585号 / 論医博第2305号 / 新制||医||1070(附属図書館) / (主査)教授 石見 拓, 教授 古川 壽亮, 教授 近藤 尚己 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM