The APC-PCI concentration as an early marker of activation of blood coagulation: a study of women on combined oral contraceptives.

BACKGROUND: The risk of venous tromboembolism (VTE) in women taking combined oral contraceptives (COCs) is attributed to changes in coagulation and fibrinolysis. The impact of the COCs may be greater in women with preexisting thrombophilic defects. Nevertheless most women who suffer from venous thrombosis do not have any of the well known hereditary or acquired risk factors. A simple and sensitive marker of"thrombogenicity" has not been identified. OBJECTIVES: To investigate the effects of two different monophasic combined oral contraceptives (COCs) on the plasma concentrations of activated protein C-inhibitor of protein C ( APC-PCI) and on comparable hemostatic factors in fertile women. METHOD: Forty four healthy nulliparous women with regular menstrual periods were included and randomly assigned to start with a monophasic preparation containing 30µg ethinylestradiol and 150µg levonogestrel (LNG/EE) or a preparation containing 30µg ethinylestradiol and 150 ug desogestrel (DG/EE). After a wash out period of two months, treatment with the alternate preparation was initiated and continued for two more cycles. RESULTS: The plasma concentration of the APC-PCI complex and thrombin-antithrombin complex (TAT) increased during treatment with the two COCs. During DG/EE treatment the APC-PCI complex increased significantly more than during LNG/EE (p<0,01).The plasma concentration of D-dimer did not increase during OC treatment. CONCLUSION: The APC-PCI complex concentration, which serves as a marker for thrombin generation and indicates hypercoagulability, was increased during COC treatment compared to baseline. The method is a sufficiently sensitive marker to detect even small differences in the activation of coagulation.

Increased levels of an apoptotic product in the sera from women with pre-eclampsia.

Pre-eclampsia is associated with both maternal and foetal complications. Several studies have shown increased trophoblast apoptosis in the placenta of women with this condition. The aim of this study was to investigate whether increased apoptosis can be detected as elevated levels of an apoptotic product in serum samples from women with pre-eclampsia. For this purpose, we used the M30-Apoptosense ELISA assay, which measures a neo-epitope of cytokeratin 18 that is exposed after cleavage by caspases during apoptosis of epithelial cells (M30 antigen). The M30-antigen concentrations were measured in the sera of 15 healthy pregnant women and 15 patients with pre-eclampsia (gestation weeks 24-34). Patients with pre-eclampsia had significantly higher serum M30-antigen concentrations, median 120 U/L, compared to 15 healthy pregnant women matched for pregnancy length, median 104 U/L (p = 0.01). This is consistent with previous findings of increased trophoblast apoptosis in women with pre-eclampsia and raises the possibility that M30-antigen can be used as a serum marker for the severeness of this condition for the mother and child.

Different secretion patterns of matrix metalloproteinases and IL-8 and effect of corticotropin-releasing hormone in preterm and term cervical fibroblasts.

The aims of the present study were to compare the levels of mRNA and protein expression of matrix metalloproteinase (MMP)-1, -3, -8 and -9 in human cervical tissue in preterm and term labor as well as not in labor and to determine if corticotropin-releasing hormone (CRH) has an effect on MMP-1, -3 and interleukin (IL)-8 secretion in both preterm and term cervical fibroblasts. Cervical biopsies were taken from 60 women: 18 at preterm labor, 7 at preterm not in labor, 18 at term labor and 17 at term not in labor. ELISA and Immulite were used for protein and real-time RT-PCR for mRNA analysis. Cervical fibroblast cultures were incubated for 18 h with different CRH concentrations (10(-13)-10(-6) M). The mRNA expression of MMP-1, -3 and -9 was higher in laboring groups compared with term not in labor. Protein levels of MMP-8 and -9 were higher in term in labor group compared with non-laboring groups. There were no significant differences in mRNA and protein expression between the preterm and respective term control groups. CRH significantly increased secretion of IL-8 in preterm and term cervical fibroblasts compared with controls. The secretion of IL-8 and MMP-1 was significantly higher and MMP-3 secretion lower in preterm cervical fibroblasts. In conclusion, cervical ripening at preterm seems to be a similar inflammatory process as at term with CRH involved. However, preterm and term cervical fibroblasts might have different phenotypes based on different secretion patterns of IL-8, MMP-1 and MMP-3.