PREECLAMPSIA IS ASSOCIATED WITH DEPRESSED FIBRINOLYSIS IN PLACENTA

Objective: To measure the molecular markers of the coagulation-fibrino lytic system, plasminogen activator inhibitor 1 (PAI-1), thrombin-anti thrombin III complex (TAT), and D-dimer, in amniotic fluid (AF), mater nal plasma, and placenta, as well as the effect of thrombin on PAI-1 p roduction by term decidual cells and to evaluate the regulatory mechan isms of the fibrinolysis system in the local state of the placenta. Me thods: AF was obtained by amniocentesis done for genetic indication an d during the elective cesarean section. Blood samples were collected b y venipuncture at 17-20 weeks and at term. Placental tissue was homoge nized in Tri-HCl buffer with Tween-80. The term decidual cells were cu ltured by the gradient percoll method. PAI-1 and D-dimer were measured by an enzyme-linked immunoassay. TAT was measured by an enzyme immuno assay method. Results: PAI-1 and TAT levels in AF (809 +/- 79 and 113 +/- 30 ng/ml [mean +/- SE], respectively) are extremely higher than in maternal plasma (P < 0.001) during normal pregnancy at term. A three- to four-fold higher PAI-1 level was found in the homogenates of decid ua as compared with that in villi and amniotic membrane (P < 0.01). As to the preeclampsia, significantly higher levels of PAI-1, TAT, and D -dimer (1,474.5 +/- 254.7, 5,000 +/- 2,531, and 132 +/- 28 ng/ml, resp ectively) were found in AF and placental decidua (1,164 +/- 132 ng/mg of protein), as compared with normal values (P < 0.01). Thrombin induc ed PAI-1 production by decidual cells in a time/dose-dependent manner. Conclusion: The increased decidual PAI-1 level, resulting in the alte rnation of the hypercoagulation and depressed fibrinolysis in placenta , might be involved in the pathogenesis of preeclampsia.