Differential platelet activation and thrombo-inflammatory mechanisms in early onset and late onset preeclampsia

Introduction: Preeclampsia (PE) is characterized by de novo onset of hypertension after 20 weeks of gestation with subtypes of early (delivered before 34 weeks) and late onset (delivered after 34 weeks) diagnosis. Early-onset PE (EOPE) is commonly associated with placental pathology and adverse maternal and neonatal outcomes. In contrast, late-onset PE (LOPE) is mostly associated with maternal factors and relatively more favorable perinatal outcomes. However, biomarkers and mechanistic differences between EOPE and LOPE remain unknown. Thrombo-inflammatory pathways play an important role in pregnancy complications. We have shown that maternal platelet activation causes inflammasome activation in trophoblast cells, resulting in a PE-like phenotype. However, whether maternal platelet activation and the associated inflammasome activation play mechanistic roles in EOPE versus LOPE remain unknown.

Method: We collected whole blood, platelets, plasma and placenta from patients with EOPE, LOPE and gestationally age matched healthy pregnancies. Clinical parameters including maternal age, gestational age, sFlt-1 and blood pressure was recorded. Platelet activation was evaluated in whole blood using flow cytometry for CD41, CD62P (P-selectin) and αIIbβIII integrin expression in unactivated state and upon ADP activation. IL-1β was measured in plasma using ELISA as a marker for inflammation. Furthermore, VCAM-1 was evaluated using ELISA as a marker of endothelial dysfunction.

Results: The patients in EOPE and LOPE groups had similar age, hypertension and proteinuria. However, plasma sFlt-1 was higher and offspring birth weight was lower in EOPE pregnancies compared to LOPE. Basal platelet activation was increased in both EOPE and LOPE compared to respective controls and was higher in LOPE pregnancies compared to EOPE pregnancies. Platelet activation was correlated with sFlt-1 levels only in LOPE. However, the tendency of agonist (ADP) mediated platelet activation was similar in both groups. IL-1β and VCAM-1 levels were increased in both EOPE and LOPE pregnancies. However, while IL-1β correlated with platelet activation and endothelial dysfunction in LOPE, no correlation was found in EOPE. No correlation was found between VCAM-1 and other parameters.

Conclusion: These findings identify that platelet activation and thrombo-inflammation is differentially regulated in LOPE vs EOPE. Furthermore, platelet activation, inflammation (IL-1β), endothelial dysfunction (VCAM-1) and disease severity (sFlt-1) correlated only in LOPE. This supports the role of maternal factors (e.g. platelets) involved in LOPE which ultimately results in placental dysfunction and increased sFlt-1. On the other hand, EOPE pregnancies are suggestive to be of placental origin eventually resulting in deficits in maternal health.

Conflict of Interest:

None

Publikationsverlauf

Artikel online veröffentlicht:
13. Februar 2025