Effective tranexamic acid concentration for 95% inhibition of tissue-type plasminogen activator-induced hyperfibrinolysis in full-term pregnant women: a prospective interventional study.

Abstract

Postpartum haemorrhage is the leading cause of maternal mortality and morbidity worldwide. Tranexamic acid (TXA) has been shown to reduce blood loss and blood product transfusion requirements. Despite clinical evidence, further studies are needed to better define the pharmacokinetic and pharmacodynamic characteristics of TXA in pregnant women. The objective of our prospective observational ex-vivo study was to define the effective TXA concentration required to inhibit 95% (EC95) of tissue-type plasminogen activator (t-PA)-induced fibrinolysis in full-term pregnant women. Hyperfibrinolysis was induced by adding supraphysiologic concentration of t-PA to blood samples obtained from 30 full-term pregnant women and 10 healthy nonpregnant female volunteers. Increasing TXA concentrations (0--40 μg/ml) were then spiked into the blood samples and inhibition of fibrinolysis was assessed using the lysis index at 30 min of the ROTEM measured on EXTEM and NATEM tests. Effective TXA concentrations required to achieve EC95 were extrapolated using nonlinear regression. EC95 were compared between groups using an extra sum-of-squares F test. EC95 in pregnant women was 14.7 μg/ml (95% CI 12.4--17.5 μg/ml) on EXTEM and 11.2 μg/ml (95% CI 8.3--15.1 μg/ml) on NATEM tests. These values were significantly higher than those obtained in volunteers: 8.7 μg/ml (95% CI 5.5--13.9 μg/ml) and 6.8 μg/ml (95% CI 5.3--8.8 μg/ml), respectively (both P < 0.001). Our results suggest a higher fibrinolytic potential in pregnant women compared with nonpregnant women.