Acute endothelial tissue plasminogen activator release in pregnancy

Abstract

Objective: Pregnancy is associated with marked changes in vascular physiology and an increased risk of thrombosis. The aim of the study was to assess the effect of pregnancy on the acute release of tissue plasminogen activator (t-PA) from the endothelium.

Methods and results: Ten primigravida pregnant women were recruited in the third trimester of pregnancy (week 36 +/- 1) and compared with 20 age-matched non-pregnant women (day 9.8 +/- 0.3 of menstrual cycle). Blood flow and plasma fibrinolytic factors were measured in both forearms by venous occlusion plethysmography and blood sampling, respectively, during unilateral brachial artery infusions of bradykinin (100-1000 pmol min(-1)). Pregnant women had higher plasma plasminogen activator inhibitor type 1 (PAI-1) antigen concentrations (77.1 +/- 12.4 vs. 21.5 +/- 9.8 ng mL(-1); P = 0.004) that resulted in lower basal t-PA/PAI-1 ratios (0.2 +/- 0.1 vs. 0.6 +/- 0.1; P = 0.02) and plasma t-PA activity concentrations (0.17 +/- 0.02 vs. 0.58 +/- 0.06 IU mL(-1); P < 0.0004). In both groups, bradykinin caused dose-dependent increases in blood flow and local release of plasma t-PA antigen and activity (P < 0.005 for all). Both the plasma t-PA/PAI-1 ratios and the net release of active t-PA were markedly reduced in pregnant women (P < 0.05 for both). Area under the curve for net active t-PA release was reduced by 36%.

Conclusions: Pregnancy is associated with major perturbations of endogenous fibrinolytic capacity with an overwhelming increase in plasma PAI-1 concentrations and an inadequate release of active t-PA. These prothrombotic effects may, in part, explain the increased risk of arterial and venous thrombosis in pregnant women.