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Grand Rounds

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

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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

METHODS:

  • 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)

RESULTS:

  • 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

CONCLUSION:

  • 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

Learn More – Primary Sources:

Optimal use of intravenous tranexamic acid for hemorrhage prevention in pregnant women

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Related ObG Topics:

Results From the Landmark Trial on Tranexamic Acid for Postpartum Hemorrhage
Cost-Effectiveness of Routine TXA Treatment for PPH in the US
Meta-Analysis: Is There an Association Between TXA and Increased Risk for Thromboembolic Events?
Does Prophylactic TXA Reduce Postpartum Hemorrhage?
Cochrane Review: TXA for Postpartum Hemorrhage – Safe and Effective?

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