Plasminogen activator inhibitors (PAI‐1 and PAI‐2) in normal pregnancies, pre‐eclampsia and hydatidiform mole

Abstract

Objective To examine the behaviour of the major inhibitors of fibrinolysis (PAI‐1 and PAI‐2) in normal pregnancy and pregnancy complicated by either pre‐eclampsia or hydatidiform mole. Design Prospective study. Setting Antenatal Clinic and Maternity Hospital. Subjects Eleven women with established pre‐eclampsia and eleven women, matched by age, parity, and duration of pregnancy who were undergoing uncomplicated pregnancy. Two women having surgery for hydatidiform mole. Main outcome measure Plasma levels of PAI‐1 and PAI‐2 antigens determined by sensitive specific ELISA. Functional identification of PAI‐2 by nondenaturing gel electrophoresis with overlay zymography. Results In pre‐eclampsia PAI‐2 antigen was significantly lower than in normal pregnancy (105.3 ± 34.9 versues 187.1 ± 67.9 ng/ml; P<0.001). In contrast PAI‐1 antigen was significantly higher in pre‐eclampsia than in normal pregnancy (170.7 ± 71.2 versus 113.8 ± 35.6 ng/ml; P<0.05). In consequence the ratio of PAI‐1/PAI‐2 increased markedly in pre‐eclampsia (2.5 versus 0.6). No PAI‐2 was detected in plasma of women with hydatidiform moles. Conclusions PAI‐2 levels fell significantly in pre‐eclampsia probably as a result of decreased placental mass or function. The raised PAI‐1 level in pre‐eclampsia may reflect a response to hypertension or renal damage that is not specific to pregnancy or may reflect altered placental function. The use of the ratio of PAI‐1/PAI‐2 assists in separating normal from abnormal pregnancies.

Preeclampsia and Extracellular Vesicles

“…Alternatively, changes in the phenotype of EVs could also cause increased coagulation. Certain pro-coagulatory molecules (e.g., PAI-1) also have important roles in EEV generation [90, 91]. Studies exploring the link between pro-coagulant factors and EV generation in preeclampsia may elucidate the mechanism that links endothelial dysfunction with widespread coagulation.…”

The Diabetes and Pre-eclampsia Intervention Trial

“…Plasminogen activator inhibitor‐1 (PAI‐1) is synthesised predominantly by endothelial cells and is a marker of endothelial activation, while PAI‐2 is synthesised by the placenta. The PAI‐1/PAI‐2 ratio decreases in normal pregnancy, but is high in pre‐eclampsia owing to endothelial cell activation and placental insufficiency [15] and, as such, the PAI‐1/PAI‐2 ratio may be a useful discriminator between normal and pre‐eclamptic pregnancies [16,17].…”

Tumour cell u‐PA as a cause of fibrinolytic bleeding in metastatic disease

“…Routine haematological studies were performed by standard methods. Tissue plasminogen activator (t-PA) and plasminogen activator inhibitors 1 and 2 (PAI-1 and PAI-2) levels were determined by specific ELISAs (MacGregor et al, 1987;Booth et al, 1988;Reith et al, 1993;respectively). U-PA was quantified using the TintElize:u-PA ELISA (Biolpool, Umea, Sweden).…”