Abstract Number: PB2573
Meeting: ISTH 2020 Congress
Background: International trials support the efficacy of tranexamic acid (TXA) for early treatment of severe hemorrhage. However, the optimal dose of TXA for hemorrhage prevention at delivery is unknown and often extrapolated from non-pregnant populations.
Aims: Since pregnant women and newborns are particularly vulnerable populations, our objective was to determine the minimum TXA dose that effectively inhibits clot lysis.
Methods: We enrolled 30 pregnant women undergoing scheduled cesarean delivery in an open-label, nonrandomized, dose escalation study. Subjects were divided into 3 cohorts receiving 5, 10 or 15 mg/kg (max 1g) of intravenous TXA at time of umbilical cord clamping. Inclusion criteria were >34 wks gestation and normal renal function. Primary end points were pharmacokinetic and pharmacodynamic profiles. Rotational thromboelastometry (ROTEM) of tissue plasminogen activator-spiked samples was used to evaluate pharmacodynamic profiles 10 min, 30-60 min, 1.5-4 hr, 4-6 hr, 7-8 hr and 24 hr after TXA administration. Safety was assessed by plasma thrombin generation, D-dimer, and TXA levels in breast milk.
Results: There were no serious adverse events including hemorrhage or venous thromboembolism. Plasma concentrations of TXA increased in a dose-proportional manner (Figure 1). Plasma TXA exceeded 10 µg/mL more than 1 hr after administration for all TXA doses tested. Maximum lysis was less than 17% for a majority of women, including all women receiving 5 mg/kg (Figure 2). Median estimated blood loss for cohorts receiving 5, 10, or 15 mg/kg TXA was 750, 750 and 700 mL, respectively. Plasma thrombin generation and D-dimer were not significantly different in any cohort. Breast milk concentrations of TXA were 1% or less than maternal plasma concentrations.
Conclusions: TPA-modified ROTEM enables assessment of TXA pharmacodynamic responses in real time. A single dose of approximately 0.5 g of intravenous TXA is sufficient to safely inhibit fibrinolysis for more than 1 hr after administration.
To cite this abstract in AMA style:Ahmadzia H, Luban N, Li S, Guo D, Mistza A, Gobburu J, Berger J, James A, Wolberg A, van den Anker J. Optimizing Tranexamic Acid Dosing for Hemorrhage Prevention in Pregnant Women [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/optimizing-tranexamic-acid-dosing-for-hemorrhage-prevention-in-pregnant-women/. Accessed October 19, 2021.
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