Concentration-effect relationship for tranexamic acid inhibition of tissue plasminogen activator-induced fibrinolysis in vitro using the viscoelastic ClotPro® TPA-test.

BACKGROUND: Tranexamic acid is an antifibrinolytic drug that is commonly administered for obstetric haemorrhage. Conventional viscoelastic tests are not sensitive to tranexamic acid, but the novel ClotPro® TPA-test can measure tranexamic acid-induced inhibition of fibrinolysis. We aimed to evaluate the TPA-test in pregnant and non-pregnant women. METHODS: We performed an in vitro study of whole blood samples spiked with tranexamic acid from pregnant women in the first, second, and third trimester (n=20 per group) and from non-pregnant women (n=20). We performed ClotPro TPA-tests of whole blood sample and ClotPro EX-tests, FIB-tests, and TPA-tests. RESULTS: Clot lysis was inhibited in a concentration-dependent manner up to a tranexamic acid concentration of 6.25 mg L-1. At tranexamic acid concentrations of 12.5 mg L-1 and above, clot lysis was completely inhibited. The concentration-effect relationship of tranexamic acid did not differ in a clinically important manner in blood from pregnant women across all three trimesters or from non-pregnant controls. A median maximum lysis cut-off value of at9 least 16% (25-75th percentiles 15-18), a median clot lysis time of 3600 s (25-75th percentiles 3600-3600), or both was associated with a tranexamic acid concentration of least 12.5 mg L-1. CONCLUSIONS: The ClotPro® TPA-test is sensitive in detecting inhibition of fibrinolysis by tranexamic acid in whole blood samples of pregnant and non-pregnant women. The concentration-effect relationship of tranexamic acid to inhibit fibrinolysis in whole blood did not differ for women in the first, second, and third trimester or for non-pregnant women.

Periodontitis, a marker of risk in pregnancy for preterm birth.

BACKGROUND: Why chronic periodontitis may induce an inflammatory response with premature pregnancy termination is unclear. AIMS: (1) To assess if periodontitis predicts premature gestation; (2) to study amniotic fluid cytokines and periodontitis variables in early-stage pregnancy. MATERIAL AND METHODS: A periodontal examination and collection of amniotic fluid was performed (weeks 15-20) of pregnancy in 36 women at risk for pregnancy complications. Amniotic fluid (bacteria), vaginal smears and intra-oral plaque samples were studied. Cytokine levels in amniotic fluid were studied in relation to other study variables. RESULTS: Periodontitis was diagnosed in 20% of normal and in 83% of preterm birth cases (p<0.01). Bacteria were never found in the amniotic fluids studied. Sub-gingival plaque samples including bacteria in the orange and red complexes were found in 18% of full-term 100% of preterm cases (p<0.001) and total colony-forming units (CFUs) were higher in preterm birth (p<0.01). Amniotic levels of interleukin (IL)-6 and prostaglandin-E2 (PGE2) were higher in preterm cases (p<0.001). Amniotic IL-6 (r=0.56, p<0.01) and PGE2 (r=0.50, p<0.01) cytokine levels were correlated with CFU from sub-gingival plaque samples (r2=0.44). The odds ratio of preterm delivery and having periodontitis was 20.0 (95% confidence interval (CI): 2.0-201.7, p<0.01). The odds of >60 CFU in sub-gingival plaque and preterm birth was 32.5:1 (95% CI: 3.0-335.1, p<01). CONCLUSIONS: Pregnant women with findings of elevated amniotic fluid levels of PGE2, IL-6 and IL-8 in the 15-20 weeks of pregnancy and with periodontitis are at high risk for premature birth. The implication of this is that periodontitis can induce a primary host response in the chorioamnion leading to preterm birth.