Tissue plasminogen activator levels change with plasma fibrinogen concentrations during pregnancy

Abstract

To investigate the relationship between coagulation activities and the fibrinolytic system during normal pregnancy, we measured the plasma concentrations of coagulation factors, antithrombin III (AT III), D-dimer, tissue plasminogen activator (tPA), total protein S (TPS), and plasminogen activator inhibitor type 1 (PAI-1) in 436 apparently healthy pregnant, postpartum, and nonpregnant women. There were no significant changes in AT III, TPS, and factor XI concentrations during pregnancy and puerperium. However, factor VII, VIII, IX, and XII activities increased gradually as pregnancy progressed, reached maximum values in the third trimester, and returned to nonpregnant levels by 5-8 weeks postpartum. Plasma D-dimer levels in the third trimester of pregnancy were 1.23+/-0.42 micro g/ml, significantly higher than for the first trimester (0.34+/-0.16 micro g/ml, P<0.01). The tPA antigen levels averaged 1.8-fold higher in the late third trimester than in the first trimester; the plasma fibrinogen concentrations averaged 1.6-fold higher in the late third trimester than in the first trimester. Compared to the peak values during pregnancy, tPA levels averaged 39.8% lower and plasma fibrinogen concentrations averaged 40.0% lower at 5-8 weeks postpartum. The tPA levels correlated strongly with the plasma fibrinogen concentrations ( r=0.52, P<0.01). In short, this study shows that tPA levels change in parallel with plasma fibrinogen concentrations during and after normal pregnancy.

Coagulation and fibrinolytic system protein profiles in women with normal pregnancies and pregnancies complicated by hypertension

“…In our group of longitudinally studied women, fibrinogen increased significantly in early pregnancy compared with prepregnancy and remained high during late pregnancy. Others have found very similar increases in fibrinogen from first to third trimester [8], though reports evaluating fibrinogen longitudinally, beginning before pregnancy and longitudinally through pregnancy are lacking. We did not detect any difference in fibrinogen in women who later developed CH, though preeclampsia is known to be a hypercoagulable state, primarily due to increases in thrombin and markers of thrombin activity, [9, 19, 20].…”

“…Indeed, clot stability is favored during pregnancy because concentrations of PAI-1 increase during pregnancy [8, 24, 25]. Reported increases in PAI-1 during pregnancy begin as early as the second trimester to the third trimester [8, 25].…”

“…T-PA is produced by endothelial cells, secreted locally in response to endothelial injury, and in the presence of fibrin, is a potent activator of plasminogen, a crucial step in fibrin degradation [5]. T-PA increases during pregnancy; however, increases in PAI-1 supersede those in T-PA thereby maintaining a procoagulable environment [8]. Though coagulation processes are predominant over fibrinolysis during pregnancy, D-Dimer, a product of fibrin degradation, increases with progressing pregnancy indicating a functionally active fibrinolytic system [8].…”

“…T-PA increases during pregnancy; however, increases in PAI-1 supersede those in T-PA thereby maintaining a procoagulable environment [8]. Though coagulation processes are predominant over fibrinolysis during pregnancy, D-Dimer, a product of fibrin degradation, increases with progressing pregnancy indicating a functionally active fibrinolytic system [8]. …”

Transfusion and coagulation management in major obstetric hemorrhage

“…[39, 40] Of note, fibrinogen levels increase with advancing gestation and in the third-trimester are higher than those in non-pregnant women (Table 2). [41–47]…”