Fibrinolysis during normal human pregnancy: complex inter-relationships between plasma levels of tissue plasminogen activator and inhibitors and the euglobulin clot lysis time.

Although it has been previously considered that blood fibrinolytic capacity is reduced during pregnancy, this has been disputed. Also the mechanisms underlying any change in fibrinolysis in pregnancy require clarification. We have therefore measured the plasma activity of tissue plasminogen activator (t-PA) and inhibitors (t-PAi) and the concentration of the pregnancy specific inhibitor (PA12) antigen, as well as the euglobulin clot lysis time (ECLT) during normal pregnancy. Plasma concentrations of fibrinogen, plasminogen, fibrin(ogen) degradation products (FDP) and cross-linked products (D-dimer) were also monitored. We confirm a marked reduction of the fibrinolytic activity of the plasma euglobulin fraction from the second trimester, and a parallel reduction in t-PA and increase in t-PAi activities, with rapid return to non-pregnant levels post-partum. In contrast, PAI2, whilst undetectable in non-pregnant control plasma, was already measurable in the first trimester, increased through pregnancy, and remained at a high concentration up to at least 48 h post-partum. Fibrinogen and plasminogen concentrations rose progressively through pregnancy and FDP and D-dimer were frequently detectable in late pregnancy plasma. Changes in the ECLT and plasma t-PA and t-PAi activities in pregnancy cannot therefore be directly related to the concentration of PAI2 antigen. Also, despite the apparent marked reduction in fibrinolytic capacity fibrin(ogen) breakdown products are frequently present in increased plasma concentrations in late pregnancy.