Elevated tissue plasminogen activator as a potential marker of endothelial dysfunction in pre-eclampsia: Correlation with proteinuria

Abstract

Objective: To clarify the role played by endothelial cell production of fibrinolytic factors in normal pregnancy and pre-eclampsia. Design: A longitudinal study performed during normal pregnancy and a cross sectional study performed in healthy and pre-eclamptic pregnant women in the third trimester of pregnancy. Setting: Department of Obstetrics and Gynaecology, University Hospital of S. João, Porto, Portugal. Population: Fourteen normal pregnant women followed through the three trimesters of gestation. Two groups of women (normal, n = 56; pre-eclamptic, n = 37) evaluated at the third trimester of gestation. Methods: Measurement of platelet number, plasma levels of fibrinogen, tissue plasminogen activator (t-PA) antigen, plasminogen activator inhibitor-1 (PAI-1) activity, and fibrin fragment D-dimer. Main outcome measures: Pre-eclampsia, proteinuria. Results: All the substances, except platelet count, increased significantly throughout normal pregnancy. Comparison of the values in the third trimesters of normal and pre-eclamptic pregnancies showed similar values for the fibrinogen and platelet counts, and higher values of t-PA (almost twice normal median value; P < 0.0001), PAI-1 and D-dimer in the pre-eclamptic women. t-PA correlated positively and significantly with the degree of proteinuria in pre-eclamptic women (r = 0.575, P = 0.0002). Conclusion: These findings suggest that elevated t-PA antigen may reflect endothelial disturbance in pre-eclampsia, and may be a potential biomarker of risk.