Isolation of a new specific plasminogen activator inhibitor from pregnancy plasma.

A specific plasminogen activator inhibitor was isolated from the plasma of pregnant women by matrix-bound, cross reacting monoclonal antibodies against placental plasminogen activator inhibitor. The pregnancy plasma plasminogen activator inhibitor (PP-PA-I) was found to be immunologically different from the inhibitor produced by endothelial cells. Its molecular weight was 70 000 daltons. It formed complexes with urokinase (u-PA) and with plasminogen activator of the tissue type (t-PA), similar to those formed by the placental plasminogen activator inhibitor (PI-PA-I). It did not inhibit plasmin. For measuring PP-PA-I, an enzyme-linked immunosorbent assay (ELISA) was designed using monoclonal and polyclonal antibodies against the placental inhibitor. Concentrations of PP-PA-I increased successively during pregnancy, and fell sharply after delivery. This inhibitor could not be detected in normal non-pregnancy plasma. The results indicate that the inhibitor isolated from pregnancy plasma is responsible for the depressed fibrinolytic activity during pregnancy, and that the placenta is the source of the inhibitor.