This proposal has three aims to characterize the relationship between aspirin therapy, platelet function response, and prevention of hypertensive disorders of pregnancy (HDP) through a prospective, cohort study using pharmacokinetics, pharmacodynamics, pharmacogenomics and bioinformatics. The results of this proposal will provide necessary data for prospective study on individualized aspirin dose adjustment for prevention of HDP.
This proposal has four aims to characterize the relationship between aspirin therapy, platelet function response, and prevention of HDP through a prospective, cohort study using pharmacodynamics, pharmacogenomics and bioinformatics. The results of this proposal will provide necessary data for prospective study on individualized aspirin dose adjustment for prevention of HDP. Aim 1: Establish pharmacodynamic endpoints for aspirin in prevention of HDP Hypothesis: PFA-100 closure time and serum thromboxane/urinary dehydrothromboxane-B2 (dTX-B2) are pharmacodynamic markers of aspirin response and are predictive of HDP high risk pregnant patients. Aim 2: Explore aspirin pharmacogenetics by assessing the relationship between platelet receptor genotype, aspirin response, and prevention of HDP Hypothesis: Platelet receptor genotype is associated with race and may result in reduced platelet response to aspirin therapy, and increased incidence of HDP. Aim 3: Assess the utility of circulating microRNA as a marker of aspirin response in pregnancy and risk of HDP Hypothesis: Quantitative expression of selected miRNAs are biomarkers for response to aspirin therapy and risk of HDP. Aim 4: Evaluate aspirin pharmacokinetics/pharmacodynamics Hypothesis: Individual factors influence aspirin pharmacokinetics/pharmacodynamics and may impact individual dosing of aspirin
Study Type
OBSERVATIONAL
Enrollment
130
Aspirin 81mg daily PO
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, United States
Aim 1: PFA-100 closure time and risk of hypertensive disorder of pregnancy (HDP)
Difference in first trimester PFA-100 closure time between patients started on aspirin who do and do not develop HDP
Time frame: 8 months (delivery)
Aim 2: Pharmacogenomics of aspirin
Difference in PFA-100 closure time with aspirin therapy based on platelet receptor genotype
Time frame: 2 weeks
Aim 3: MicroRNAs and HDP
Regression analysis to evaluate how miRNAs 223, 126, 155, 181a, 18a, 16 levels in first trimester are associated with risk of HDP
Time frame: 8 months (delivery)
Aim 4: Aspirin pharmacokinetics in pregnancy
Define population based pharmacokinetic model of aspirin in first trimester of pregnancy taking into consideration individual factors (gestational age, race, BMI, genotype)
Time frame: 2 weeks
Aim 1: Aspirin response
Multiple logisitic regression analysis to evaluate factors (BMI, race, gestational age, genotype) associated with rate of nonresponse to aspirin therapy defined as (PFA-100\>150s)
Time frame: 2 weeks
Aim 1: Prediction of HDP
ROCC curve to determine threshold PFA-100 closure time after 1 week of aspirin therapy that is predictive of HDP
Time frame: 8 months (delivery)
Aim 1: First trimester serum thromboxane and risk of HDP
Comparison between first trimester serum thromboxane in those with and without hypertensive disorder of pregnancy
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Time frame: 8 months (delivery)
Aim 1: Third trimester serum thromboxane and risk of HDP
Comparison between third trimester serum thromboxane in those with and without hypertensive disorder of pregnancy
Time frame: 8 months (delivery)
Aim 2: Pharmacogenomics and Pregnancy outcome
Multiple regression analysis taking into consideration platelet receptor genotype, race, BMI, and other clinical characteristics and prediction of HDP
Time frame: 8 months (delivery)
Aim 3: MicroRNA profile and aspirin therapy
Paired comparison to evaluate how miRNAs 223, 126, 155, 181a, 18a, 16 levels change before and after aspirin therapy
Time frame: 2 weeks
Aim 4: Salicylic acid level and Serum Thromboxane
Association between serum salicylic acid with aspirin therapy and serum thromboxane with aspirin therapy
Time frame: 2 weeks
Predictors of preterm birth
Multivariable logistic regression to evaluate markers predictive of preterm birth
Time frame: 8 months (delivery)
Predictors of preeclampsia
Multivariable logistic regression to evaluate markers predictive of preeclampsia and preterm preeclampsia
Time frame: 8 months (delivery)