Background and Goal of Study: Postpartum hemorrhage (PPH) is the leading cause of maternal mortality and morbidity worldwide. Tranexamic acid (TXA) has been shown to reduce blood loss and blood products transfusion requirements (1). Despite clinical evidence, further studies are needed to better define the pharmacokinetic and pharmacodynamic characteristics of TXA in pregnant women. The first objective of our prospective ex-vivo study was to define the minimum TXA concentration required to inhibit fibrinolysis in full-term pregnant women. The second was to compare these results to those obtained in healthy non-pregnant
volunteers.
Materials and methods: After IEC approval, maximal fibrinolysis was induced by adding supraphysiologic concentration of
tissue-type plasminogen activator (tPA) to blood samples obtained from 30 fullterm pregnant women and 10 volunteers who gave written informed consent. Increasing TXA concentrations (0 to 40 μg/ml) were then spiked into the blood samples and inhibition of fibrinolysis was assessed using the LI30 of the ROTEM measured on EXTEM and NATEM tests. Effective TXA concentrations required to achieve 95% inhibition of fibrinolysis (EC95) were extrapolated using nonlinear regression. EC95 were compared between groups using the Fisher test. Results and discussion: EC95 in pregnant women was 14.7 μg/ml (CI 95%: 12.417.5 μg/ml) on EXTEM and 11.2 μg/ml (CI 95%: 8.315.1 μg/ml) on NATEM tests. These values were significantly higher than those obtained in volunteers (8.7 μg/ml (CI 95%: 5.513.9 μg/ml) and 6.8 μg/ml (CI 95%: 5.38.8 μg/ml) respectively; both p< 0.001 (fig 1)).
Conclusions: Despite a decreased fibrinolytic activity associated with a prothrombotic state in the 3rd trimester of
pregnancy (2), our results suggest a higher fibrinolytic potential in pregnant compared to non-pregnant
women. Further studies are required to define the optimal TXA dose in PPH. A first step might be to determine if the TXA dose used actually is able to fully inhibit tPA-induced fibrinolysis in our ex-vivo model.
References:
1. Novikova N, et al. Cochrane Database Syst Rev. 2015 CD007872
2. Hellgren M. Semin Thromb Hemost. 2003 29(2):12530

Effective tranexamic acid concentration for 95% inhibition of tissue-type plasminogen activator-induced fibrinolysis in full-term pregnant women