Association of Placenta‐Derived Extracellular Vesicles with Preeclampsia and Associated Hypercoagulability: A clinical observational study

OBJECTIVE Preeclampsia (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 center at the Department of Obstetrics and Gynecology, Tianjin Medical University. POPULATION We collected blood samples and clinical information from 54 PE patients, 33 normally pregnant women with 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 analyzed using flow cytometry, coagulation tests, and ELISA. MAIN OUTCOME MEASURES The primary outcome was plasma pcEVs 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 NW women to PE patients (IQR for NW: 206/µl [116-255], NP: 1,108 [789-1,969], and PE: 8,487 [4,991-16,752]) 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.