Haemostatic, fibrinolytic and endothelial variables in normal pregnancies and pre‐eclampsia

OBJECTIVE: To determine the behaviour of the coagulation variables antithrombin III (ATIII), protein C, thrombin/antithrombin III (TATIII); fibrinolytic activity, tissue plasminogen activator antigen (t-PA), plasminogen activator inhibitors (PAI) 1 and 2, and endothelial involvement by fibronectin assay in normal and pre-eclamptic pregnancies. DESIGN: Longitudinal and cross-sectional observational study. SETTING: Antenatal clinic and maternity hospital. SUBJECTS: Thirty-six primigravid normotensive caucasian patients, four of whom subsequently developed pre-eclampsia, and 12 patients with established pre-eclampsia. MAIN OUTCOME MEASURES: Plasma levels of PAI-1, PAI-2 and t-PA antigen were determined using an ELISA technique as were TATIII complex levels of fibronectin. ATIII and protein C plasma levels were assayed using chromogenic substrate techniques. RESULTS: PAI-1 and PAI-2 antigen levels rose progressively throughout normal pregnancy. Among the established pre-eclamptic group compared with matched normal pregnancies, the PAI-2 antigen level was significantly lower (48.5 +/- 22.8 versus 183.5 +/- 37.4; P < 0.001), the PAI-1 antigen level was significantly higher (122 +/- 34.4 versus 79.2 +/- 19.7; P < 0.001), ATIII activity was significantly lower (87.8 +/- 27.1 versus 110.9 +/- 19.3; P < 0.001) and TATIII complex levels were significantly higher (16.9 +/- 6.4 versus 10.2 +/- 5.9; P < 0.001). Among the four initially normotensive patients who subsequently developed pre-eclampsia, fibronectin levels were significantly elevated from as early as nine weeks of gestation. CONCLUSION: Significantly elevated levels of PAI-1 and fibronectin occurring early in pregnancies that subsequently develop pre-eclampsia suggest that these variables may have predictive values. PAI-2 would seem to be a marker of placental function in pre-eclampsia while increased t-PA and TATIII complex levels reflect the severity of the condition.