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Evidence summaries

Tranexamic Acid for Preventing Postpartum Haemorrhage

Tranexamic acid appears to decrease postpartum blood loss after vaginal birth or caesarean section compared with placebo or no treatment, without increasing thromboembolic events. Level of evidence: "B"

A meta-analysis 3 included 18 RCTs with 3846 subjects, with 1935 patients receiving tranexamic acid (TXA). The studies were of poor to moderate quality. Prophylactic TXA administration was associated with a decreased incidence of postpartum haemorrhge (PPH) after delivery (odds ratio [OR], 0.32; 95% CI, 0.17 to 0.59; P = .0006), a reduction in mean blood loss by 149.1mL (95% CI, 112.9 to 185.2; P < .00001), and a reduction in red blood cell transfusions (OR, 0.28; 95% CI, 0.15 to 0.49; P < .00001) while also being associated with a reduction in the use of additional uterotonics (OR, 0.45; 95% CI, 0.30 to 0.66; P < .00001). Minor side effects were more common in those who received TXA (OR, 2.51; 95% CI, 1.69-3.74; P < .00001). There appeared to be no increased risk of venous thromboembolism and no difference in length of hospital stay associated with TXA use.

Another meta-analysis 2 included 25 RCTs with 4747 subjects. TXA resulted in a reduced intra-, postoperative, and total blood loss by a mean volume of 141.25 mL (95% CI -186.72 to -95.79, P < 0.00001), 36.42 mL (95% CI -46.50 to -26.34, P < 0.00001), and 154.25 mL (95% CI -182.04 to -126.47, P < 0.00001) in caesarean section. TXA administration in vaginal delivery was associated with a reduced intra-, postoperative, and total blood loss by a mean volume of 22.88 mL (95% CI -50.54 to 4.77, P = 0.10), 41.24 mL (95% CI -55.50 to -26.98, P < 0.00001), and 84.79 mL (95% CI -109.93 to -59.65, P < 0.00001). In addition, TXA could lower the occurrence rate of PPH and severe PPH, and reduce the risk of blood transfusions. No increased risk of deep vein thrombosis was associated with TXA usage.

A multicenter, double-blind, randomized, controlled trial 4 included 3891 subjects. The primary outcome off PPH occurred in 156/1921 women (8.1%) in the TXA group and in 188/1918 (9.8%) in the placebo group (RR 0.83; 95% CI, 0.68 to 1.01; P=0.07). TXA group had a lower rate of provider-assessed clinically significant PPH than those in the placebo group (7.8% vs. 10.4%; RR 0.74; 95% CI, 0.61 to 0.91; P=0.004; P=0.04 after adjustment for multiple comparisons post hoc) and also received additional uterotonic agents less often (7.2% vs. 9.7%; RR 0.75; 95% CI, 0.61 to 0.92; P=0.006; adjusted P=0.04). Other secondary outcomes did not differ significantly between the two groups. The incidence of thromboembolic events in the 3 months after delivery did not differ significantly between the TXA and the placebo (0.1% and 0.2%, respectively; relative risk, 0.25; 95% CI, 0.03 to 2.24).

A Cochrane review [Abstract] 1 included 12 studies with a total of 3 285 subjects at low risk of excessive bleeding undergoing elective caesarean section (n=2453) or spontaneous birth (n=832). Blood loss greater than 400 ml or 500 ml was less common in women who received tranexamic acid compared with placebo or no intervention (RR 0.52, 95% CI 0.42 to 0.63; 6 trials, n=1398) as well as loss more than 1000 ml (RR 0.40, 95% CI 0.23 to 0.71; 6 trials, n=2093). Tranexamic acid decreased the incidence of blood loss greater than 1000 mL in women with caesarean seciton (RR 0.43, 95% CI 0.23, 0.78; 4 trials, n=1534). Mean blood loss (from delivery until two hours postpartum) was lower in the group of women who received intravenous tranexamic acid postpartum (mean difference (MD) 77.79 mL, 95% CI -97.95, -57.64; 5 trials, n=1186). All women in both studies received routine uterotonics. Additional medical interventions and blood transfusions were less frequent in the tranwxamic acid group. No serious side effects were reported with tranexamic acid, though no data were available of thromboembolic episodes.

Comment: The quality of evidence is downgraded by study quality (unclear allocation concealment and blinding in half of the trials).

    References

    • Novikova N, Hofmeyr GJ, Cluver C. Tranexamic acid for preventing postpartum haemorrhage. Cochrane Database Syst Rev 2015;(6):CD007872. [PubMed]
    • Li C, Gong Y, Dong L et al. Is prophylactic tranexamic acid administration effective and safe for postpartum hemorrhage prevention?: A systematic review and meta-analysis. Medicine (Baltimore) 2017;96(1):e5653. [PubMed]
    • Alam A, Choi S. Prophylactic Use of Tranexamic Acid for Postpartum Bleeding Outcomes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Transfus Med Rev 2015;29(4):231-41.[PubMed]
    • Sentilhes L, Winer N, Azria E et al. Tranexamic Acid for the Prevention of Blood Loss after Vaginal Delivery. N Engl J Med 2018;379(8):731-742. [PubMed]

Primary/Secondary Keywords