Journal Club Papers
Paper 1: The effect of tranexamic acid on postpartum bleeding in women with moderate and severe anaemia (WOMAN-2): an international, randomised, double-blind, placebo-controlled trial
The WOMAN-2 Trial Collaborators, The Lancet, October 2024. DOI: 10.1016/S0140-6736(24)01749-5
- This randomized, double blinded, placebo-controlled trial recruited women in labour with moderate to severe anaemia (haemoglobin <100g/L) from 4 countries (Pakistan, Nigeria, Tanzania and Zambia).
- 15,068 women were randomized to receive 1g of tranexamic acid (n=7,580) or placebo (n=7,488) within 15 minutes of cord clamping to prevent postpartum haemorrhage.
- The primary outcome was postpartum haemorrhage, defined as an estimated blood loss >500ml or any volume sufficient to compromise haemodynamic stability.
- Tranexamic acid did not alter the risk of postpartum haemorrhage among women with moderate to severe anaemia. Postpartum haemorrhage occurred among 7% (530/7579) in the tranexamic acid group vs 6.6% (497/7478) in the placebo group (risk ratio 1.05 [95%CI 0.94, 1.19]).
- There was also no difference in other bleeding related outcomes; estimated blood loss (309.8 vs 310ml), corrected 24h haemoglobin (82.2 vs 82.1 g/L), maternal death or near miss within 24h (1.6% vs 1.8%) or maternal death in hospital (0.1% vs 0.1%)
- No vascular occlusive events were reported in either group.
Unfortunately, this impressively huge trial did not find tranexamic acid prevents postpartum haemorrhage among women in labour with moderate to severe anaemia.
Paper 2: Tranexamic acid for postpartum bleeding: a systematic review and individual patient data meta-analysis of randomised controlled trials
Ker et al, The Lancet, October 2024. DOI: 10.1016/S0140-6736(24)02102-0
Published in The Lancet on the same day as the WOMAN-2 trial this meta-analysis aimed to investigate whether tranexamic acid is effective and safe for bleeding complications related to postpartum haemorrhage. This meta-analysis included the results from the WOMAN-2 trial.
- The authors only included trials that were prospectively registered, randomized, placebo-controlled and included at least 500 women. Studies also had to be considered at low risk of bias for random sequence generation and allocation concealment (improving the overall quality of the included trials).
- Notably, results for prevention and treatment trials were pooled.
- Five trials were included. Only one treatment trial was included; the original WOMAN trial that reported a 19% reduced risk for maternal death due to bleeding for tranexamic acid vs placebo among women with an established postpartum haemorrhage (RR 0.81 [95%CI 0.65,1.00]). The remaining 4 were prevention trials.
- For the primary outcome of life-threatening bleeding within 24 hours of birth (defined as death or surgical interventions for bleeding), tranexamic acid was associated with a 23% risk reduction (OR 0.77 [95%CI 0.63, 0.96]; 178/27,300 vs 230/27,093).
- However, the significant finding was mainly driven by the positive results of the single treatment trial, the WOMAN trial. An analysis limited to the 4 remaining trials - all assessing tranexamic acid to prevent bleeding - results in a non-significant effect on the primary outcome OR 0.72 (95%CI 0.42, 1.22); 23/17,264 among tranexamic acid exposed vs 32/17,108 placebo; 4 trials).
- Unsurprisingly, the primary outcome occurred far more frequently in the treatment trial (WOMAN trial), compared to the four prevention trials. This likely further explains the fact why the WOMAN trial had a dominant influence in the final results of the meta-analysis.
- The authors also assessed thromboembolic events across the five trials, reassuringly tranexamic acid did not alter the risk of these events (OR 0.96 [95%CI 0.65,1.41]; 50/26,571 vs 52/26,373).
While this meta-analysis reports a benefit of tranexamic acid for life threatening bleeding, the pooling of prevention and treatment trials makes interpretation challenging. Removing the only treatment trial from the meta-analysis revealed no significant effect of tranexamic acid for preventing life threatening bleeding. It is reassuring that across 50,000 pregnancies, they found no increase in thromboembolic events for tranexamic acid when compared with placebo.
When considering the findings of both Lancet publications, a clinically useful interpretation may be that tranexamic acid is useful for treating postpartum bleeding (ie giving the drug when the bleeding is already brisk), but is not useful for preventing postpartum haemorrhage (ie giving the drug before heavy bleeding is sighted, in the hope of avoiding it in the first place).