Pregnancy-induced changes in the fibrinolytic balance: evidence for defective release of tissue plasminogen activator and increased levels of the fast-acting tissue plasminogen activator inhibitor.

Pregnancy is accompanied by an increased risk of thromboembolic disease. One contributing factor to such disease in the nonpregnant patient is disordered fibrinolysis. It has been suggested that defective fibrinolysis may occur in pregnancy, but this defect has been poorly characterized. In the present study of 52 women with normal pregnancies and 56 nonpregnant control women, we found a marked change in levels of releasable tissue plasminogen activator in pregnant women beginning in the first trimester. Whereas nonpregnant women demonstrated releasable levels of tissue plasminogen activator of 0.74 +/- 0.15 IU/ml of plasma, in the pregnant women the amount released was only 0.06 +/- 0.02 IU/ml of plasma (p less than 0.01). These levels were observed beginning in the first trimester. Levels of the recently described fast-acting tissue plasminogen activator inhibitor increased significantly throughout pregnancy. Values ranged from 8.40 +/- 0.27 IU/ml of plasma in the first trimester to 9.92 +/- 0.09 IU/ml of plasma in the third trimester (p less than 0.05) compared with the level of 8.46 +/- 0.19 IU/ml of plasma in nonpregnant subjects. These data suggest that alterations both in releasable tissue plasminogen activator and in the fast-acting tissue plasminogen activator inhibitor contribute to the physiologic hypercoagulable state of pregnancy.