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.

Classification of Preeclamptic Placental Extracellular Vesicles Using Femtosecond Laser-fabricated Nanoplasmonic Sensors and Machine Learning

“…67 Confirming the importance of differences in the lipid content of EVs from preeclampsia, Chen et al, have recently published that placental EVs that have vesicle-surface exposed phospatidyl serine (identified by annexin V binding) are increased in preeclamptic pregnancies. 68 However, the exact role of placental EV-lipid content and its role in normotensive and preeclamptic pregnancies have not been fully elucidated to date.…”

Molecular Advances in Preeclampsia and HELLP Syndrome

“…In the study conducted by Molvarec et al, preeclamptic women had a higher concentration of vWF: Ag but a normal level of multimers compared to a healthy control group [ 22 ]. Chen et al stated that the increased levels of vWF persist during the first week after delivery in preeclamptic women [ 24 ].…”

“…It is also important to identify fluctuations in ADAMTS13 and vWF levels or modification of their function during normal pregnancy. According to Chen et al, in normal pregnancy, vWF is characterized by an enhanced adhesion ability, resulting in a pregnancy-related hypercoagulable state [ 24 ]. Moreover, in the study of Drury Stewart et al, a statistically significant increase in vWF: Ag (vWF antigen) was described in normal pregnancy, while vWFpp (vWF propeptide) also increased at a later stage of gestation [ 23 ].…”

“…The question is whether ADAMTS13 could be considered a reliable biomarker for the diagnosis of TTP, since there are several studies supporting a statistically significant decrease in ADAMTS13 in other TMAs, such as HELLP syndrome/preeclampsia [ 2 , 17 , 18 , 19 , 20 , 21 , 22 , 24 ]. ADAMTS13 activity values can vary from 12% to 43% in HELLP syndrome.…”

Viscoelastic Hemostatic Assays for Postpartum Hemorrhage

“…Preeclampsia and related hypertensive disorders (e.g., hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome, eclampsia, etc.) cause hemostatic aberrancies which most often manifest as hypercoagulability [136]. Although the pathophysiology of preeclampsia is not agreed upon and may involve a genetic predisposition to thrombophilia [137], evidence suggests the etiology relates to abnormal placentation, lack of spiral artery remodeling, and subsequent uteroplacental insufficiency and trophoblast ischemia [138].…”