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

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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.