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Persistent Thromboxane Biosynthesis Despite Aspirin Therapy Predicts Preeclampsia

Year: 2026

Type: article

Abstract: Preeclampsia (PE) is associated with enhanced platelet activation, with thromboxane A₂ playing a key pathogenic role. Urinary 11-dehydro-thromboxane B₂ (TXM) reflects in vivo platelet activation. Although low-dose aspirin (ASA) is recommended for PE prevention in high-risk pregnancies, variable thromboxane suppression may lead to persistent platelet activation. This study aimed at identifying platelet-derived predictors of PE in high-risk women receiving ASA and assessing biomarkers improving risk stratification. This observational study included 25 high-risk pregnant women on ASA and 12 with physiological pregnancies. Clinical evaluation and blood/urine sampling were performed at baseline (T0), and at 21 (T4) and 27 (T5) weeks. Urinary TXM and percentage inhibition (<75% = reduced inhibition) were assessed. Platelet biomarkers included thrombopoietin (TPO), glycocalicin (GC), P-selectin, and CD40L. Late-onset PE occurred in 6/25 (24%) high-risk women and in none of the controls. TXM levels were higher in high-risk versus physiological pregnancies (p=0.009), especially at T4-T5 (p<0.0001). Women developing PE had higher TXM at T4 (adjusted p=0.014) and lower TXM inhibition (51% vs 81%; p=0.020). Reduced inhibition (<75%) was associated with increased PE risk (44.4% vs 14.3%; OR 4.8). TPO showed a different longitudinal pattern according to PE occurrence (time-by-outcome interaction p=0.036). Glycocalicin showed higher estimated values at baseline in women who developed PE (p=0.048), but the time-specific contrast was attenuated after Holm adjustment (adjusted p=0.19). Incomplete thromboxane suppression during ASA therapy is associated with PE. TXM, together with opposite trends of TPO and GC, identifies a profile consistent with altered platelet homeostasis and possible changes in platelet turnover, potentially enhancing risk prediction in high-risk pregnancies.

Source: Blood Advances

DOI: 10.1182/bloodadvances.2026021230