Decrease in protein C inhibitor activity and acquired APC resistance during normal pregnancy

Background: Since protein C inhibitor (PCI) inhibits activated protein C (A PC) and a number of proteases, one would expect lower concentrations of PCI in a hypercoagulable state due to increased consumption of the inhibitor. Normal pregnancy is associated with a state of activated hemostasis, where response to APC is depressed. We aimed to study whether PCI function varies during normal pregnancy, and assess the relationship between this inhibito r and acquired APC resistance. Methods: PCI activity in plasma was tested during pregnancy and postpartum in 28 healthy pregnant women without factor V Leiden Arg(506) - Gln mutatio n and in 14 non-pregnant female controls. The PCI levels determined in the present study was compared to the APC ratio (APC-r), we investigated previo usly, in the same samples. Results: The levels of PCI in the pregnant group, as compared to that in th e control group (4.74 +/- 0.48), gradually decreased from the first to the third trimester, i.e., 3.30 +/- 1.31 mu g/mL in week 12 (p < 0.001), 2.66 /- 1.44 mu g/mL in week 20 (p < 0.001), 1.92 +/- 1.18 mu g/mL in week 28 (p < 0.001), 1.30 +/- 0.94 mu g/mL in week 32 (p < 0.001) and 1.49 +/- 1.12 m u g/mL in week 37 (p < 0.001). After delivery, they rose to 5.02 +/- 1.93 m u g/mL, similar to that in the controls (p > 0.05). The values of APC-r sho wed the same tendency during gestation and postpartum. Conclusion: With advance of normal pregnancy, decreasing PCI function corre sponds to increasing APC resistance, probably due to that activated hemosta sis acts as a link connecting the two variables.