Aspirin for preeclampsia prevention: Pharmacodynamics and pharmacogenomics of platelet response and pregnancy outcomes

阿司匹林预防子痫前期：血小板反应和妊娠结局的药效学和药物基因组学

• 批准号: 9907567
• 负责人: Rupsa Chaudhury Boelig
• 金额: $ 19.5万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9907567
• 关键词: Address; Adult; Adverse effects; African American; Aspirin; Bioinformatics; Biological Assay; Blood; Blood Platelets; Blood Vessels; Cardiovascular system; Clinical; Clinical Pharmacology; Clinical Research; Data; Development; Disease; Dose; Effectiveness; Enrollment; Equipment; Event; First Pregnancy Trimester; Future; Genetic; Genotype; Hematology; High Risk Woman; High-Risk Pregnancy; Human Resources; Incidence; Individual; Institution; Maternal and Child Health; Maternal-fetal medicine; Measures; Medicine; Methods; MicroRNAs; Modification; Neonatal; Neonatal Mortality; Observational Study; Outcome; PAWR gene; Participant; Pathogenesis; Pathway interactions; Patients; Pharmacodynamics; Pharmacogenetics; Pharmacogenomics; Pharmacology; Phase; Physiology; Pilot Projects; Platelet Activation; Platelet Function Tests; Platelet Inhibitors; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Pregnant Women; Premature Birth; Prevention; Prospective Studies; Prospective cohort study; Protocols documentation; Reporting; Research; Resources; Retrospective Studies; Risk; Scientist; Thrombin Receptor; Time; United States; Universities; Urine; Variant; base; circulating microRNA; clinical care; cohort; cost estimate; dose individualization; experience; follow-up; high risk; improved; individual response; individual variation; insight; investigator training; laboratory experience; maternal morbidity; maternal outcome; microRNA biomarkers; neonatal morbidity; neonatal outcome; novel; personalized care; pharmacodynamic biomarker; platelet function; pregnancy disorder; pregnancy hypertension; pregnancy prevention; pregnant; prospective; randomized trial; receptor; research study; response; response biomarker; risk minimization; sample collection; therapy development; urinary

PROJECT SUMMARY Background: Hypertensive disorders of pregnancy (HDP), preeclampsia and gestational hypertension, are significant drivers of preterm birth and both neonatal and maternal morbidity. Platelet activation is associated with the pathogenesis of preeclampsia. Aspirin is an inhibitor of platelets and has been shown to reduce the risk of preeclampsia in high risk pregnant patients, however, the response is dose dependent, as are the risks of adverse effects, and the optimal dose is not known. Aspirin is well documented to have a variable individual response in platelet inhibition, however there is currently no method for determining the optimal dose for preeclampsia prevention for each individual. Objective: This proposal has three aims to characterize the relationship between aspirin therapy, platelet function response, and prevention of HDP through a prospective observational study of pregnant women taking daily aspirin for prevention of preeclampsia. The results of this proposal will enable a future study on a protocol for individualized aspirin dose modification for HDP prevention in order to maximize benefit and minimize risks. Methods: This is a prospective observational cohort pilot study over 24 months of pregnant women at high risk for preeclampsia who are recommended aspirin therapy. Participants will be enrolled in the first trimester and have baseline labwork done prior to the initiation of aspirin, follow up labwork done 1-2 weeks after initiation of aspirin, and pregnancies followed for outcomes. Aim 1 will evaluate how the PFA-100 closure time and urinary dehydrothromboxane B2 levels, both markers of platelet function, are correlated with the development of preeclampsia HDP. Aim 2 will evaluate the pharmacogenomics of a platelet receptor variant and its association with response to aspirin therapy and development of HDP. Aim 3 will evaluate select microRNAs as biomarkers for response to aspirin therapy and risk of preeclampsia in pregnant women.

项目摘要 背景：怀孕的高血压疾病（HDP），先兆子痫和妊娠 高血压是早产的重要驱动因素以及新生儿和母体发病率。 血小板激活与先兆子痫的发病机理有关。阿司匹林是 血小板已被证明可降低高风险孕妇的先兆子痫的风险， 但是，反应是剂量依赖的，不良影响的风险也是如此，最佳 剂量不知道。阿司匹林有充分的文献记载，可以在血小板中具有可变的个体反应 但是，抑制作用，目前尚无确定最佳剂量的方法 每个人预防先兆子痫。 目的：该提议的三个旨在表征阿司匹林之间的关系 通过前瞻性治疗，血小板功能反应和预防HDP 对孕妇每天预防先兆子痫的观察性研究。这 该提案的结果将使以后的关于个性化阿司匹林剂量方案的研究 预防HDP的修改，以最大程度地提高利益并最大程度地降低风险。 方法：这是一项超过24个月怀孕的前瞻性观察队列试点研究 建议接受阿司匹林治疗的先兆子痫的高风险。参与者会 入学前三个月，并在阿司匹林启动之前完成了基线实验室。 启动阿司匹林后1-2周进行的后续实验室工作，然后怀孕 结果。 AIM 1将评估PFA-100的闭合时间和尿路脱水液盒如何 B2水平是血小板功能的两个标记，都与 子痫前期HDP。 AIM 2将评估血小板受体变体的药物基因组学和 它与对阿司匹林疗法的反应和HDP的发展有关。 AIM 3将评估 选择microRNA作为对阿司匹林治疗的反应和子痫风险的生物标志物 孕妇。