Grand Rounds

What is the Optimal Dosage of TXA for Postpartum Hemorrhage Prevention?

BACKGROUND AND PURPOSE:

Ahmadzia et al. (AJOG, 2021) performed a dose-finding study to determine the optimal tranexamic acid dose needed to prevent postpartum hemorrhage

Open-label, dose ranging study
Participants
- ≥34 week’s gestation
- Normal renal function
- Udergoing scheduled cesarean delivery
Interventions
- IV TXA at umbilical cord clamping (max dose 1000 mg)
  - 5 mg/kg
  - 10 mg/kg
  - 15 mg/kg
Study design
- Pharmacodynamic profiles done at time points up to 24 hours after TXA administration | TXA inhibits the degradation (lysis) of fibrin to byproducts (e.g., D-dimer)
- Safety was assessed by plasma thrombin generation, D-dimer, and TXA concentrations in breast milk
Primary outcomes
- Pharmacokinetic and pharmacodynamic profiles
- TXA plasma concentration of >10 μg/mL and maximum lysis of <17% (defined as therapeutic targets)

30 women
Plasma concentrations of TXA increased in a dose-proportional manner
- The lowest dose cohort received an average of 448±87 mg TXA
- The range of doses in this cohort was 448 mg to 632 mg
Plasma TXA exceeded 10 μg/mL and maximum lysis was <17% at >1 hour after administration for all tranexamic acid doses tested
Median estimated blood loss
- 5 mg/kg: 750 mL
- 10 mg/kg: 750 mL
- 15 mg/kg: 700 mL
Safety assessment
- Plasma thrombin generation were not increased with higher TXA concentrations
- D-dimer changes from baseline were not different among the cohorts
- Breast milk TXA concentrations were 1% or less than maternal plasma concentrations
There were no serious adverse events including venous thromboembolism

A prophylactic, low dose (5 mg/kg) of TXA effectively achieved pharmacokinetic and pharmacodynamic targets for at least an hour after administration
Safety profile was reassuring
The authors propose a dosage of 600 mg of TXA be investigated further in future trials and in addition state

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