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

项目总结 背景：妊娠期高血压疾病、子痫前期和妊娠 高血压是早产以及新生儿和产妇发病率的重要驱动因素。 血小板活化与子痫前期的发病机制有关。阿司匹林是一种抗癌药物 它能降低高危孕妇患先兆子痫的风险， 然而，这种反应是剂量依赖的，不良反应的风险也是如此，最佳的 剂量尚不清楚。阿司匹林在血小板中有不同的个体反应是有充分证据的。 抑制，但目前还没有方法来确定最佳剂量 针对每个个体的子痫前期预防。 目的：这项提议有三个目的来描述阿司匹林和阿司匹林 前瞻性研究HDP的治疗、血小板功能反应和预防 孕妇每日服用阿司匹林预防子痫前期的观察研究。这个 这项提案的结果将使未来对阿司匹林个体化剂量方案的研究成为可能 对HDP预防进行修改，以最大限度地提高收益并最大限度地降低风险。 方法：这是一项怀孕24个月的前瞻性观察队列先导研究。 推荐使用阿司匹林治疗的先兆子痫高危妇女。参与者将是 在怀孕的前三个月登记，并在开始服用阿司匹林之前完成基线实验室工作， 在服用阿司匹林后1-2周进行跟踪实验室工作，并对 结果。目的1将评估PFA-100关闭时间和尿脱氢血栓素 B2水平是血小板功能的两个标志，与高血压的发生有关。 先兆子痫HDP。目的2将评估一种血小板受体变异体和 它与阿司匹林治疗反应和HDP发生的关系。AIM 3将评估 选择microRNAs作为阿司匹林治疗反应和先兆子痫风险的生物标志物 怀孕的女人。

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.