Platelet protease-activated receptor 4 genotype and response to aspirin in pregnancy
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...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-08-01
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| Series: | Blood Vessels, Thrombosis & Hemostasis |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2950327225000427 |
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| author | Rupsa C. Boelig James V. Michael Antonios Tawk Tingting Zhan Joanna S. Y. Chan Walter K. Kraft Steven E. McKenzie |
| author_facet | Rupsa C. Boelig James V. Michael Antonios Tawk Tingting Zhan Joanna S. Y. Chan Walter K. Kraft Steven E. McKenzie |
| author_sort | Rupsa C. Boelig |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-b03bb087519f451db6cef46978e2d27c |
| institution | Kabale University |
| issn | 2950-3272 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Blood Vessels, Thrombosis & Hemostasis |
| spelling | doaj-art-b03bb087519f451db6cef46978e2d27c2025-08-20T05:08:36ZengElsevierBlood Vessels, Thrombosis & Hemostasis2950-32722025-08-012310008510.1016/j.bvth.2025.100085Platelet protease-activated receptor 4 genotype and response to aspirin in pregnancyRupsa C. Boelig0James V. Michael1Antonios Tawk2Tingting Zhan3Joanna S. Y. Chan4Walter K. Kraft5Steven E. McKenzie6Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA; Department of Pharmacology, Physiology, and Cancer Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA; Correspondence: Rupsa C. Boelig, Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Thomas Jefferson University, 833 Chestnut St, Philadelphia, PA 19107;Cardeza Foundation for Hematologic Research, Department of Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PACardeza Foundation for Hematologic Research, Department of Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PADivision of Biostatistics, Department of Pharmacology, Physiology, and Cancer Biology, Thomas Jefferson University, Philadelphia, PADepartment of Pathology and Genomic Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PADepartment of Pharmacology, Physiology, and Cancer Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PACardeza Foundation for Hematologic Research, Department of Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PAAbstract: 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.http://www.sciencedirect.com/science/article/pii/S2950327225000427 |
| spellingShingle | Rupsa C. Boelig James V. Michael Antonios Tawk Tingting Zhan Joanna S. Y. Chan Walter K. Kraft Steven E. McKenzie Platelet protease-activated receptor 4 genotype and response to aspirin in pregnancy Blood Vessels, Thrombosis & Hemostasis |
| title | Platelet protease-activated receptor 4 genotype and response to aspirin in pregnancy |
| title_full | Platelet protease-activated receptor 4 genotype and response to aspirin in pregnancy |
| title_fullStr | Platelet protease-activated receptor 4 genotype and response to aspirin in pregnancy |
| title_full_unstemmed | Platelet protease-activated receptor 4 genotype and response to aspirin in pregnancy |
| title_short | Platelet protease-activated receptor 4 genotype and response to aspirin in pregnancy |
| title_sort | platelet protease activated receptor 4 genotype and response to aspirin in pregnancy |
| url | http://www.sciencedirect.com/science/article/pii/S2950327225000427 |
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