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

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 versus 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.