Abstract
Background: Pre-eclampsia (P-EC) is associated with systemic inflammation, endothelial dysfunction and hypercoagulability. The role of extracellular vesicles (EVs) in coagulation disturbances affecting the development and severity of P-EC remains elusive. We aimed to evaluate the concentration of EVs expressing phosphatidylserine (PS) and specific markers in relation to the thrombin and fibrin formation as well as fibrin clot properties, in pregnant women with P-EC in comparison to healthy pregnant women of similar gestational age.Methods: Blood samples of 30 pregnant women diagnosed with P-EC were collected on the morning following admission to hospital and after delivery (mean duration 5 days). The concentration of the PS-exposing EVs (PS+ EVs) from platelets (CD42a+, endothelial cells (CD62E+), and PS+ EVs expressing tissue factor (TF) and vascular cell adhesion molecule 1 (VCAM-1) were measured by flow cytometry. Further phenotyping of EVs also included expression of PlGF. Markers of maternal haemostasis were correlated with EVs concentration in plasma.Results: Preeclamptic pregnancy was associated with significantly higher plasma levels of PS+ CD42a+ EVs and PS+ VCAM-1+ EVs in comparison with normotensive pregnancy. P-EC patients after delivery had markedly elevated concentration of PS+ CD42a+ EVs, CD62E+ EVs, TF+ EVs, and VCAM-1+ EVs compared to those before delivery. Inverse correlation was observed between EVs concentrations (PS+, PS+ TF+, and PlGF+) and parameters of overall haemostatic potential (OHP) and fibrin formation, while PS+ VCAM-1+ EVs directly correlated with FVIII activity in plasma.Conclusion: Increased levels of PS+ EVs subpopulations in P-EC and their association with global haemostatic parameters, as well as with fibrin clot properties may suggest EVs involvement in intravascular fibrin deposition leading to subsequent microcirculation disorders.
Highlights
Pre-eclampsia (P-EC) is a pregnancy-specific multisystem disorder associated with high perinatal and maternal morbidity and mortality rates, and at the same time linked to longterm health consequences for mothers and their offspring [1,2,3]
There were no significant differences in smoking status or family history of cardiovascular diseases (CVD)
Rates of previous pregnancy complications and reported positive family history of pregnancy complications were higher in the P-EC group
Summary
Pre-eclampsia (P-EC) is a pregnancy-specific multisystem disorder associated with high perinatal and maternal morbidity and mortality rates, and at the same time linked to longterm health consequences for mothers and their offspring [1,2,3]. The root cause of P-EC is considered to be a defect in early placental development, followed by generalized inflammation and progressive endothelial damage predisposing to coagulation activation. Haemostatic equilibrium shifted toward a procoagulable state in normal pregnancy is even more pronounced in P-EC, resulting in enhanced thrombin generation, increased platelet activation and deposition of microthrombi in renal and placental vasculature [4, 5]. Likewise, disseminated endothelial cell dysfunction and injury occurring in P-EC have been related to the release of placentaderived factors and their effects on the maternal vasculature. We aimed to evaluate the concentration of EVs expressing phosphatidylserine (PS) and specific markers in relation to the thrombin and fibrin formation as well as fibrin clot properties, in pregnant women with P-EC in comparison to healthy pregnant women of similar gestational age
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