Increased platelet activation and thrombo-inflammation in early and late-onset preeclampsia

Background

Preeclampsia is a vascular complication of pregnancy with limited therapeutic options. It is associated with hypertension and an increase in angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor. Based on its onset, preclampsia can be categorized into early-onset (E-PE) or late-onset (L-PE) preeclampsia. Thrombo-inflammation, hallmarked by maternal platelet activation and sterile inflammation, is associated with pathophysiology of preeclampsia. However, whether these mechanisms are differentially regulated in E-PE vs L-PE remains unknown.

Objectives

We aim to study the role of maternal platelet activation, inflammation and endothelial dysfunction in E-PE vs L-PE.

Methods

Flow-cytometry analysis of platelet activation (P-selectin and active αIIbβ3) was conducted in whole blood from pregnant women with E-PE, L-PE and gestational age-matched patients. Plasma was evaluated for interleukin (IL)-1β and soluble vascular cell adhesion molecule 1 (sVCAM-1).

Results

An increase in P-selectin and active αIIbβ3 expressing platelets in both forms of preeclampsia (n = 22) was observed compared with their gestational age-matched controls (n = 18). Similarly, an increase in plasma IL-1β and sVCAM-1 was observed in both forms of preeclampsia, suggesting inflammation and endothelial dysfunction, respectively. Maternal platelet activation (P-selectin positive platelets) was linked with disease severity (sFlt-1/placental growth factor) and maternal plasma IL-1β and sVCAM-1 only in late-onset preeclampsia. A statistically significant correlation with αIIbβ3 expressing platelets and sFlt-1, IL-1β, and sVCAM-1 was not observed.

Conclusions

These findings identify that thrombo-inflammation is regulated in L-PE and E-PE through likely disjunct mechanisms supporting a role of maternal factors (eg, maternal platelet activation) involved in L-PE. Further studies with a larger cohort of patients are required to fully elucidate the mechanistic relevance of these findings.