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.