Document Type

Article

Publication Date

8-19-2025

Comments

This article is the author's final published version in Blood Vessels, Thrombosis and Hemostasis, Volume 2, Issue 3, August 2025, Article number 100085.

The published version is available at https://doi.org/10.1016/j.bvth.2025.100085. Copyright © 2025 American Society of Hematology.

Abstract

The platelet protease-activated receptor 4 (PAR4) threonine 120 (Thr120) allele is an activating allele associated with reduced aspirin response in vitro. Aspirin is recommended in high-risk pregnancies to prevent preeclampsia and preterm birth. We evaluated the impact of PAR4 genotype on aspirin response in pregnancy, as measured by platelet function assay 100 (PFA-100) epinephrine closure time, and perinatal outcomes. We conducted a prospective cohort study of high-risk pregnant patients who took 81-mg aspirin daily. PFA-100 was assessed at baseline, 2 to 4 weeks after aspirin initiation (follow-up 1), and 28 to 32 weeks’ gestation (follow-up 2). Primary outcome was difference in PFA-100 by genotype. Exposure was defined as PAR4-Thr120 homozygous vs not. Of the 122 participants were included, 24 (19.6%) were PAR4-Thr120 homozygous, and 106 completed follow-up 1 with >75% adherence. Participants homozygous for PAR4-Thr120 had a significantly higher rate of prior preterm birth (50.0% vs 16.1%; P = .004). Genotype was not significantly associated with PFA-100 response in multivariable regression. In the subset with urinary thromboxane data available (n = 18), thromboxane levels were higher in those who were homozygous vs not (geometric mean ratio, 208 [95% confidence interval, 1.66-2.61]; P < .001) in multivariable regression. There was a higher rate of placental intervillous thrombosis, although not statistically significant (16.7% vs 3.9%; P = .08). Patients homozygous for PAR4-Thr120 had a higher incidence of prior preterm birth, a risk factor for poor perinatal outcome. Aspirin response, measured by PFA-100, was similar across genotypes, although Thr120 homozygosity may be associated with reduced thromboxane suppression and a higher rate of placental vasculopathy even with 81-mg aspirin daily.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

PubMed ID

40918740

Language

English

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