Clinical Question

Does tranexamic acid (Cyklokapron) decrease the rate of death and hysterectomy in women with postpartum hemorrhage?

Bottom Line

In this really large study, tranexamic acid did not decrease the frequency of the primary outcome of death or hysterectomy in women with postpartum hemorrhage. However, there was a very small reduction in the rate of death from bleeding in the women treated with tranexamic acid. (Level of Evidence = 1b)

Synopsis

In this multicenter international study, the research teams recruited 20,060 women, 16 years or older, with a clinical diagnosis of postpartum hemorrhage following a vaginal delivery or a cesarean delivery (clinically estimated blood loss of more than 500 mL after vaginal birth or 1,000 mL after cesarean delivery, or any blood loss associated with hemodynamic instability). With other routine interventions for bleeding, the researchers administered 1 g of tranexamic acid or placebo by slow intravenous injection (100 mg per mL intravenously at an approximate rate of 1 mL per minute). If bleeding continued after 30 minutes, or stopped and restarted within 24 hours of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given.

The authors reported no difference in the rate of the primary outcome, a composite of death from all causes or hysterectomy within 42 days of randomization. However, the authors reported there was a very small, barely statistically significant reduction in death due to hemorrhage (1.5% vs. 1.9%; P = .045) in patients who received tranexamic acid. If it takes 20,000 patients to barely achieve statistical significance, the impact cannot be all that great (number needed to treat [NNT] = 274; 95% confidence interval, 137 to 18,923). This is fairly typical of intervention trials: Ignore that the primary outcome was the same in both groups and focus on a secondary end point, which then becomes the tail wagging the dog. In the group of women given tranexamic acid one to three hours after delivery, there was more significant decrease in death from bleeding (NNT = 100).

Study design: Randomized controlled trial (double-blinded)

Funding source: Industry plus foundation

Allocation: Concealed

Setting: Other

Reference:WOMAN Trial CollaboratorsEffect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial. Lancet2017;389(10084):2105–2116.