Platelet protease-activated receptor 4 genotype and response to aspirin in pregnancy

Blood Vessels, Thrombosis & Hemostasis Pub Date : 2025-08-01 DOI:10.1016/j.bvth.2025.100085

Rupsa C. Boelig , James V. Michael , Antonios Tawk , Tingting Zhan , Joanna S. Y. Chan , Walter K. Kraft , Steven E. McKenzie

{"title":"Platelet protease-activated receptor 4 genotype and response to aspirin in pregnancy","authors":"Rupsa C. Boelig , James V. Michael , Antonios Tawk , Tingting Zhan , Joanna S. Y. Chan , Walter K. Kraft , Steven E. McKenzie","doi":"10.1016/j.bvth.2025.100085","DOIUrl":null,"url":null,"abstract":"<div><h3>Abstract</h3><div>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%; <em>P</em> = .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]; <em>P</em> < .001) in multivariable regression. There was a higher rate of placental intervillous thrombosis, although not statistically significant (16.7% vs 3.9%; <em>P</em> = .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.</div></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 3","pages":"Article 100085"},"PeriodicalIF":0.0000,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Blood Vessels, Thrombosis & Hemostasis","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2950327225000427","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}

引用次数: 0

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.

查看原文本刊更多论文

妊娠期血小板蛋白酶激活受体4基因型及对阿司匹林的反应

血小板蛋白酶激活受体4 （PAR4）苏氨酸120 （Thr120）等位基因是与体外阿司匹林反应降低相关的激活等位基因。阿司匹林被推荐用于高危妊娠，以预防先兆子痫和早产。我们通过血小板功能测定100 （PFA-100）、肾上腺素闭合时间和围产期结局来评估PAR4基因型对妊娠期阿司匹林反应的影响。我们对每日服用81毫克阿司匹林的高危孕妇进行了前瞻性队列研究。PFA-100在基线、阿司匹林起始后2 - 4周（随访1）和妊娠28 - 32周（随访2）进行评估。主要终点为基因型PFA-100的差异。暴露定义为PAR4-Thr120纯合与非纯合。在纳入的122名参与者中，24名（19.6%）为PAR4-Thr120纯合子，106名完成随访1，依从性为75%。PAR4-Thr120纯合子的参与者有更高的早产率（50.0% vs 16.1%; P = 0.004）。在多变量回归中，基因型与PFA-100反应无显著相关。在可获得尿血栓素数据的子集中（n = 18），在多变量回归中，纯合子组的血栓素水平高于非纯合子组（几何平均比，208[95%置信区间，1.66-2.61];P < .001）。胎盘绒毛间血栓发生率较高，但无统计学意义（16.7% vs 3.9%; P = 0.08）。PAR4-Thr120纯合子的患者先前早产的发生率更高，这是围产期预后不良的一个危险因素。PFA-100测量的阿司匹林反应在不同基因型中相似，尽管Thr120纯合性可能与血栓素抑制降低和胎盘血管病变发生率升高有关，即使每天服用81mg阿司匹林。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Blood Vessels, Thrombosis & Hemostasis

自引率

0.00%

发文量