Individual predictors of platelet response to aspirin therapy in pregnancy

Abstract

Aspirin (81mg daily) reduces the risk of preeclampsia in high-risk individuals, however, up to 30% of treated high-risk individuals still develop preeclampsia. Aspirin response in non-pregnant adults can vary widely. The objective of this study is to identify individual factors predictive of response to aspirin therapy in pregnancy. PFA-100 closure time is a measure of platelet response to epinephrine and is a quantitative measure of aspirin induced platelet inhibition. We conducted a prospective cohort study at Thomas Jefferson University Hospital of 130 patients with a singleton pregnancy at risk for preeclampsia and recommended aspirin therapy, 81mg daily initiated ≤16 weeks. PFA-100 closure time was analyzed at baseline and then 2-4 weeks after aspirin initiation. The primary outcome was PFA-100 closure time at follow-up #1. Predictors were evaluated with multivariable least squares model with stepwise variable selection using R package. 114 participants completed follow-up visit #1 with complete data for all variables. Average gestational age at baseline was 12.6±1.5 and at follow-up#1 was 16.0 ±2.3 weeks’ (p< 0.001). There was a significant increase in mean PFA-100 from baseline to follow-up #1 (131±39 vs 170±61, p< 0.001). In multivariable logistic regression, obesity and pre-gestational diabetes were associated with reduced aspirin response (lower PFA-100). Those with diabetes or obesity had lower mean PFA-100 at follow up in unadjusted and adjusted analyses (Figure). In contrast, Black race was associated with increased platelet response to aspirin therapy (MD 29 (95% CI 7-51), p=0.01) (Table). Baseline PFA-100 was also positively associated with follow-up PFA-100 (Table). Individuals with pre-gestational diabetes or obesity have a reduced platelet response to aspirin therapy. This is consistent with findings in non-pregnant adults. Aspirin dosing in pregnancy may need to be adjusted based on individual characteristics.View Large Image Figure ViewerDownload Hi-res image Download (PPT)