(1172) Xenobiotic transfer of tranexamic acid through an ex vivo placental perfusion model

Objective: In obstetrics, intravenous tranexamic acid (TXA) is used to treat postpartum hemorrhage via inhibition of fibrinolysis and is effective in reducing mortality from postpartum hemorrhage. TXA is not currently approved for prophylactic use of postpartum blood loss but existing meta-analyses suggest it may reduce the incidence of postpartum hemorrhage and overall blood loss. However, data on use of TXA for antepartum bleeding is limited. 

Study Design: We used an ex vivo placental perfusate model to study the rate of transfer of TXA across the placental interface. Placentas from term uncomplicated singleton pregnancies were obtained immediately after scheduled cesarean deliveries. A fetal vein-artery pair supplying a cotyledon was isolated, cannulated and perfused. Maternal circulation was also established through placental storm. After addition of TXA and antipyrine (positive control) to the system, fetal samples were collected every 15 minutes for 3 hours with two parallel closed circulations (maternal and fetal). Fetal artery pressure and pH of the maternal and fetal reservoir were monitored every 15 minutes to continuously assess the integrity of the model. Fetal vein samples were analyzed via HPLC to quantify TXA and antipyrine concentrations. 

Results: TXA rapidly crosses the placental interface within 15 minutes of administration. TXA levels in the fetal vein rose over 3 hours and was modeled with a logarithmic curve. The predicted final fetal vein concentration was 250 µM. The in vivo fetal concentration would likely be lower due to increased maternal circulating volume and renal clearance. Based on transfer seen in this ex vivo model, we would predict an in vivo fetal vein concentration of 7 µg/mL (clinical effects are seen at 10-15 mg/mL).

Conclusion: Tranexamic acid rapidly crosses the placental interface in an ex vivo model. However, the fetal vein concentration is reduced compared to maternal concentration. This suggests that in vivo use may be ethically safe to test as expected fetal concentrations would be below the clinically effective threshold.