# Tailoring low-dose aspirin to prevent preeclampsia: translational and biomarker insights

**Authors:** Hira Sohail, Xiao Lin Hua

PMC · DOI: 10.3389/fmed.2026.1754660 · Frontiers in Medicine · 2026-02-18

## TL;DR

This paper reviews biomarkers that could help tailor low-dose aspirin use to prevent preeclampsia, but notes most are not yet ready for clinical use.

## Contribution

The paper synthesizes current evidence on genetic, platelet, and angiogenic biomarkers for aspirin response in preeclampsia prevention.

## Key findings

- Genetic variants, platelet assays, and angiogenic biomarkers show potential for understanding aspirin response variability.
- Most biomarker evidence comes from observational studies and lacks validation in pregnant populations.
- Angiogenic biomarkers are useful later in pregnancy but not for guiding early aspirin use.

## Abstract

Low-dose aspirin is the only pharmacological intervention with consistent evidence for reducing the risk of preeclampsia in high-risk pregnancies. However, substantial interindividual variability in response has prompted interest in biomarkers that may improve understanding of aspirin responsiveness and disease heterogeneity.

This narrative review synthesizes translational, observational, and clinical literature examining genetic, platelet, and angiogenic biomarkers in the context of aspirin prophylaxis for preeclampsia. Relevant studies were identified through targeted searches of major biomedical databases to provide a conceptual overview of current evidence.

Genetic variants related to aspirin metabolism and platelet function, platelet indices and aggregation assays, and angiogenic biomarkers such as soluble fms-like tyrosine kinase-1 and placental growth factor have been investigated as potential tools to refine risk stratification and elucidate variability in aspirin response. While these biomarkers offer important mechanistic insight, most evidence derives from association studies and observational cohorts. Genetic testing and platelet function assays lack validation in pregnant populations, standardized thresholds, and randomized evidence, supporting their use to guide aspirin initiation, dosing, or monitoring. Angiogenic biomarkers have an established diagnostic and prognostic role later in pregnancy but remain investigational for first-trimester risk stratification and are not used to modify aspirin therapy.

Biomarkers provide valuable insight into the biological heterogeneity underlying preeclampsia and aspirin response; however, biomarker-guided aspirin strategies remain investigational. In the absence of randomized trials, aspirin prophylaxis should continue to follow established guideline-based risk assessment, with biomarker-informed approaches reserved for future research.

## Linked entities

- **Chemicals:** aspirin (PubChem CID 2244)
- **Diseases:** preeclampsia (MONDO:0005081)

## Full-text entities

- **Genes:** ITGA2 (integrin subunit alpha 2) [NCBI Gene 3673] {aka BR, CD49B, FMAIT3, GPIa, HPA-5, VLA-2}, REN (renin) [NCBI Gene 5972] {aka ADTKD4, HNFJ2, RTD}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, ACVR2A (activin A receptor type 2A) [NCBI Gene 92] {aka ACTRII, ACVR2}, TFPI (tissue factor pathway inhibitor) [NCBI Gene 7035] {aka EPI, LACI, TFI, TFPI1}, CES1 (carboxylesterase 1) [NCBI Gene 1066] {aka ACAT, CE-1, CEH, CES2, HMSE, HMSE1}, FLT1 (fms related receptor tyrosine kinase 1) [NCBI Gene 2321] {aka FLT, FLT-1, VEGFR-1, VEGFR1}, PGF (placental growth factor) [NCBI Gene 5228] {aka D12S1900, PGFL, PIGF, PLGF, PlGF-2, SHGC-10760}, GP1BA (glycoprotein Ib platelet subunit alpha) [NCBI Gene 2811] {aka BDPLT1, BDPLT3, BSS, CD42B, CD42b-alpha, DBPLT3}, ENG (endoglin) [NCBI Gene 2022] {aka END, HHT1, ORW1}, NOS3 (nitric oxide synthase 3) [NCBI Gene 4846] {aka EC-NOS, ECNOS, MYMY8, NOSIII, cNOS, eNOS}, COX1 (cytochrome c oxidase subunit I) [NCBI Gene 4512] {aka COI, MTCO1}, HLA-G (major histocompatibility complex, class I, G) [NCBI Gene 3135] {aka MHC-G}, PLAT (plasminogen activator, tissue type) [NCBI Gene 5327] {aka T-PA, TPA}, PON1 (paraoxonase 1) [NCBI Gene 5444] {aka ESA, MVCD5, PON}, FGG (fibrinogen gamma chain) [NCBI Gene 2266], PTGS1 (prostaglandin-endoperoxide synthase 1) [NCBI Gene 5742] {aka COX1, COX3, PCOX1, PES-1, PGG/HS, PGHS-1}
- **Diseases:** proteinuria (MESH:D011507), hypoxia (MESH:D000860), maternal organ dysfunction (MESH:D009102), obesity (MESH:D009765), endothelial dysfunction (MESH:D014652), diabetes (MESH:D003920), PE (MESH:D011225), inflammation (MESH:D007249), platelet aggregation (MESH:D001791), fetal growth restriction (MESH:D005317), maternal death (MESH:D063130), LDA (MESH:D009800), cardiovascular diseases (MESH:D002318), impaired placental vascularization (MESH:D010922), gastrointestinal discomfort (MESH:D005767), hypertension (MESH:D006973), venous thromboembolism (MESH:D054556)
- **Chemicals:** PGI2 (MESH:D011464), nitric oxide (MESH:D009569), Aspirin (MESH:D001241), metformin (MESH:D008687), TXA2 (MESH:D013928), salicylic acid (MESH:D020156), 11-dehydro-thromboxane B2 (MESH:C049235), heparin (MESH:D006493), LMWH (MESH:D006495), Thromboxane (MESH:D013931), pravastatin (MESH:D017035), LDA (-), NO (MESH:D009614)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC12956531/full.md

## References

66 references — full list in the complete paper: https://tomesphere.com/paper/PMC12956531/full.md

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Source: https://tomesphere.com/paper/PMC12956531