Decrease in protein C inhibitor activity and acquired APC resistance during normal pregnancy.
BACKGROUND
Since protein C inhibitor (PCI) inhibits activated protein C (APC) 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 inhibitor 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 mutation 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 previously, in the same samples.


RESULTS
The levels of PCI in the pregnant group, as compared to that in the control group (4.74 +/- 0.48), gradually decreased from the first to the third trimester, i.e., 3.30 +/- 1.31 microg/mL in week 12 (p < 0.001), 2.66 +/- 1.44 microg/mL in week 20 (p < 0.001), 1.92 +/- 1.18 microg/mL in week 28 (p < 0.001), 1.30 +/- 0.94 microg/mL in week 32 (p < 0.001) and 1.49 +/- 1.12 microg/mL in week 37 (p < 0.001). After delivery, they rose to 5.02 +/- 1.93 microg/mL, similar to that in the controls (p > 0.05). The values of APC-r showed the same tendency during gestation and postpartum.


CONCLUSIONS
With advance of normal pregnancy, decreasing PCI function corresponds to increasing APC resistance, probably due to that activated hemostasis acts as a link connecting the two variables.
Shu
H
H
Department of Laboratory Medicine/Coagulation Research, Karolinska Institutet, Stockholm, Sweden.
Wramsby
M
M
Bokarewa
M
M
Blombäck
M
M
Bremme
K
K
D020016:Activated Protein C Resistance / Q000097:blood*; D000328:Adult; D005260:Female; D006801:Humans; D049590:Postpartum Period / Q000097:blood; D011247:Pregnancy / Q000097:blood*; D018046:Protein C Inhibitor / Q000097:blood / Q000378:metabolism*; D013997:Time Factors
D018046:Protein C Inhibitor