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PubMed · 10728028

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

H Shu·M Wramsby·M Bokarewa·M Blombäck·K Bremme
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Abstract

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. CONCLUSION: 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.

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Activated Protein C ResistanceAdultFemaleHumansPostpartum PeriodPregnancyProtein C InhibitorTime FactorsComparative StudyJournal ArticleResearch Support, Non-U.S. Gov't

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H Shu, M Wramsby, M Bokarewa, M Blombäck, K Bremme. 2000. Decrease in protein C inhibitor activity and acquired APC resistance during normal pregnancy.. https://doi.org/10.1023/a%3A1018726930407

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PubMed2000

Frequency of polymorphisms in the B-domain of factor V gene in APC-resistant patients.

In this study we investigated a group of patients in whom a resistance to APC (activated protein C) was found but no Leiden mutation existed in the presence of missense mutations in the first 1200 bp of the Exon 13 (B-domain) in the factor V (FV) gene. The determination of the APC response was performed using the Immunochrom(R) APC response Test Kit. The mutations were determined by temperature gradient gel electrophoresis and DNA sequencing. In the APC-resistant patients without the FV Leiden, we found 4 silent mutations (2298C>T, 2325T>C, 2379A>G, 2391A>G) and 4 missense mutations (2540A>C, 2663A>G, 2684A>G, 2863A>G), which code for the amino acids N789T (GenBank Accession # AF119360), K830R, H837R, and K897E. In all of the patients and controls, the polymorphisms at nucleotide positions 2391, 2663, 2684, and 2863 appeared to be associated. In the major allele all bases are A (A allele) and in the minor allele are G (G allele). A significantly lower G allele frequency was observable in the patient group than in the control group (0.14 vs. 0.31; p<0.05). The frequency of the 2540C allele, which is associated with the 2379G and the 4070G allele (non-Leiden!), did not differ significantly between the patient and the control groups. We suggest that the G allele, which is not associated with the FV Leiden mutation, as well as the [2379G; 2540C; 4070G] allele have no influence on the APC cofactor function itself, or only subtly as determined in the test systems used.

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