Coagulation status and complications of pregnancy.

INTRODUCTION: There is much interest in the relationship between coagulation status and complications of pregnancy. The thrombelastograph (TEG) has been proposed as a useful, inexpensive tool to screen for patients with hypercoagulable states. MATERIALS AND METHODS: We investigated 588 unselected pregnant women at booking, obtaining blood samples for TEG and thrombophilia investigation. Pregnancy outcome data was recorded. RESULTS: We found significant correlations between TEG parameters and the Prothrombin time (PT) and Activated Partial Thromboplastin time (APTT) (p<0.01) and with plasma Antithrombin level (p<0.01). There was no correlation between TEG and other thrombophilic defects (protein C, protein S, Factor V Leiden mutation, Prothrombin G20210A mutation, MTHFR C677T mutation and Lupus Anticoagulant). There was a significant association of TEG parameters with mid-trimester loss (MTL) but not with other adverse pregnancy outcomes. CONCLUSIONS: The correlation between TEG and PT, APTT and antithrombin level supports its value in providing a global measure of haemostasis. Coagulation status at booking is associated with increased risk of MTL but not with complications occurring later in pregnancy.

N- and C-terminal modifications of nociceptin/orphanin FQ generate highly potent NOP receptor ligands.

Previous structure-activity studies on nociceptin/orphanin FQ (N/OFQ) identified [Phe(1)Psi(CH(2)NH)Gly(2)]N/OFQ(1-13)-NH(2) and [Nphe(1)]N/OFQ(1-13)-NH(2) as a N/OFQ peptide receptor (NOP) partial agonist and pure antagonist, respectively. The addition of fluorine to the Phe(4) or the insertion of a further pair of basic amino acids Arg(14)-Lys(15) generate potent agonists. On the basis of these findings, we combined in the N/OFQ-NH(2) template the chemical modifications Arg(14)-Lys(15) and (pF)Phe(4) that increase the agonist potency with those conferring partial agonist (Phe(1)Psi(CH(2)NH)Gly(2)) or pure antagonist (Nphe(1)) properties. Twelve peptides were synthesized and pharmacologically evaluated in Chinese hamster ovary cells expressing the human recombinant NOP and in electrically stimulated mouse vas deferens and guinea pig ileum assays. All peptides behaved as NOP ligands; the chemical modifications Arg(14)-Lys(15) and (pF)Phe(4) increased ligand affinity/potency. Peptides with the normal Phe(1)-Gly(2) peptide bond behaved as full agonists, and those with the Phe(1)Psi(CH(2)NH)Gly(2) modification behaved as partial agonists, while those with the Nphe(1) modification behaved as partial agonists or pure antagonists depending on the presence or absence of the (pF)Phe(4) modification, respectively. The full agonist [(pF)Phe(4),Arg(14),Lys(15)]N/OFQ-NH(2), the partial agonist [Phe(1)Psi(CH(2)NH)Gly(2),(pF)Phe(4),Arg(14),Lys(15)]N/OFQ-NH(2), and the pure antagonist [Nphe(1),Arg(14),Lys(15)]N/OFQ-NH(2) represent the most potent peptide ligands for NOP.

The effects of folic acid supplements on coagulation status in pregnancy.

Thromboembolic disease remains the leading cause of maternal death in the UK. Recent literature has proposed that folate status is a strong predictor for venous thrombosis. Using thrombelastography (TEG((R))), we tested the hypothesis that folic acid supplementation is associated with a reduction in whole blood coagulability. Blood samples and questionnaire data were obtained at a mean gestation of 13.6 weeks (SD: 3.8, range: 6-38 weeks) from unselected consecutive women attending for their antenatal booking scan. Of 588 patients, 439 (74.7%) took folic acid. All TEG((R)) parameters were less hypercoagulable in women that had taken folic acid compared with those that had not: mean maximum amplitude (MA) 60.3 versus 62.1; mean difference 1.8; 95% confidence interval 0.8, 2.8; P = 0.0001; mean coagulation index (CI) 0.54 versus 0.85; mean difference 0.31; 95% confidence interval 0.11, 0.5; P = 0.002. There was no difference in the incidence of the homozygous MTHFR mutation in patients taking folic acid (5.53%) compared with those that were not (4.08%). This study suggests that benefit may be derived from longer-term treatment, although large multicentre studies are required to determine whether the relative hypocoagulability is associated with a reduction in risk of venous thrombosis.