BACKGROUND AND PURPOSE:

• This current Cochrane review (Shakur et al., Cochrane Database of Systematic Reviews, 2018) focused specifically at antifibrinolytic drugs for the treatment of primary PPH

METHODS:

• Systematic review and meta-analysis
• Search methods
  • Searches included: Cochrane Pregnancy and Childbirth’s Trials Register | ClinicalTrials.gov | WHO International Clinical Trials Registry Platform (ICTRP) | Reference lists of retrieved studies
• Inclusion criteria
  • RCTs
  • Studies that included antifibrinolytic drugs
    • Aprotinin | TXA | epsilon-aminocaproic acid (EACA) | Aminomethylbenzoic acid
  • Any route of administration
  • Indication: Primary PPH
• Exclusion criteria
  • Quasi-randomized trials or cross-over studies
  • Abstracts with insufficient information to assess biases
• Participants
  • Women after birth following a pregnancy of at least 24 weeks’ gestation with a diagnosis of PPH
  • Mode of birth (vaginal or cesarean), and other aspects of third stage management were not examined
• Primary outcomes
  • Mortality due to bleeding
  • All-cause mortality*
  • Serious maternal morbidity
• Secondary outcomes included mortality from other causes, shock, amount of blood loss, transfusion etc.
• Data collection and analysis
  • Two review authors independently extracted data from each study using an agreed form and checked for accuracy
  • Quality of evidence was rated as ‘high’, ‘moderate’, ‘low’ or ‘very low’ according to the GRADE criteria

RESULTS:

• 3 trials |20,412 women
  • No trials assessed EACA, aprotinin or aminomethylbenzoic acid
  • For the remaining 3 studies, standard care plus IV TXA for the treatment of primary PPH was compared to placebo or standard of care alone
• The WOMAN trial contributed over 99% of the data and was assessed as low risk of bias (for more on this study, see ‘Related ObG Topics’ below)
  • The quality of evidence varied for different outcomes
• Overall, evidence was moderate to high quality
• IV TXA reduces the risk of maternal death due to bleeding
  • Risk ratio (RR) 0.81 (95% CI, 0.65 to 1.00; two trials, 20,172 women; quality of evidence: moderate)
  • Result not impacted by mode of birth
• Timing of TXA treatment was critical for effect size
  • <1 hr: RR 0.80 (95% CI,0.55 to 1.16)
  • 1 to 3 hrs: RR 0.60 (95% CI, 0.41 to 0.88)
  • >3 hrs: RR 1.07 (95% CI, 0.76 to 1.51)
• There was no heterogeneity in the effect by mode of birth
• Fewer all cause deaths but not statistically significant
• TXA did not reduce the risk of
  • Serious maternal morbidity: RR 0.99 (95% CI, 0.83 to 1.19; one trial, 20,015 women; quality of evidence: high)
  • Hysterectomy to control bleeding: RR 0.95 (95% CI, 0.81 to 1.12; one trial, 20,017 women; quality of evidence: high)
  • Blood transfusion: RR 1.00 (95% CIm 0.97 to 1.03; two trials, 20,167 women; quality of evidence: moderate)
  • Maternal vascular occlusive events: RR 0.88 (95% CI, 0.54 to 1.43; one trial, 20,018 women; quality of evidence: moderate)
• There was an increase in the use of brace sutures (B-Lynch)  in the TXA group
  • RR 1.19 (95% CI, 1.01 to 1.41)
• There was a reduction in the need for laparotomy in the TXA group
  • RR 0.64 (95% CI 0.49 to 0.85)

CONCLUSION:

• When IV TXA was used to treat PPH
  • There as reduced mortality risk related to bleeding, regardless of mode of birth
  • No increase in risk for thromboembolic events
• Findings in obstetrics are consistent with that of trauma settings
• Authors recommend exploring other routes of administration for out-of-hospital settings where IV may not be readily accessible

Learn More – Primary Sources:

Antifibrinolytic drugs for treating primary postpartum haemorrhage

Related ObG Topics:

How Effective is Intrauterine Balloon Tamponade for Severe Postpartum Hemorrhage

Postpartum Hemorrhage Prophylaxis: The World Health Organization Recommendations

Postpartum Hemorrhage – Medications to Treat Uterine Atony 

Results From the Landmark Trial on Tranexamic Acid for Postpartum Hemorrhage

Does Prophylactic TXA Reduce Postpartum Hemorrhage?