Association of placenta-derived extracellular vesicles with pre-eclampsia and associated hypercoagulability: a clinical observational study.

ABSTRACT

OBJECTIVE: Pre-eclampsia (PE) is a pregnancy-associated condition initiated by placental factors. We have demonstrated that placental extracellular vesicles (pcEVs) cause hypertension and proteinuria in pregnant and non-pregnant mice. STUDY DESIGN: An observational study with both case-control and longitudinal designs. SETTING: A single centre at the Department of Obstetrics and Gynaecology, Tianjin Medical University. POPULATION We collected blood samples and clinical information from 54 PE patients, 33 normally pregnant women at 30-36 gestational weeks and on postpartum days 1 and 4 for the cross-sectional study, and at 22-31, 32-35 and 36-40 weeks for the longitudinal study. Non-pregnant women were also recruited. METHODS: Blood samples were analysed using flow cytometry, coagulation tests and ELISA. MAIN OUTCOME MEASURES: The primary outcome was plasma pcEV and other extracellular vesicles (EVs), and their expressions of anionic phospholipids and von Willebrand factor (VWF). Secondary variables included coagulation, ADAMTS-13 and the anionic phospholipid-binding proteins. RESULTS: Plasma pcEVs progressively increased from pregnant women during non-menstrual period (NW) to PE patients (interquartile range [IQR] for NW 206/microlitre [116-255], normal pregnancy [NP] 1108/microlitre [789-1969] and PE 8487/microlitre [4991-16 752]) and predicted PE. EVs from endothelial cells, platelets and erythrocytes accounted for <10% of pcEVs. VWF became hyper-adhesive in PE patients and contributed to the pregnancy-associated hypercoagulability. CONCLUSION: Placental, platelet- and endothelial cell-derived EVs were significantly elevated in PE patients, but only pcEVs predicted PE. These EVs played a causal role in the pregnancy-induced hypercoagulability. TWEETABLE ABSTRACT Placenta-derived extracellular vesicles predict pre-eclampsia and the associated hypercoagulability.