This review found insufficient evidence from randomised controlled trials to confirm or refute a clinically important treatment effect from tranexamic acid in postpartum bleeding. The authors' cautious conclusions appeared to reflect the evidence, but given the limited number and poor-quality of studies and potential for bias, the reliability of these conclusions is unclear.

To evaluate the effectiveness and safety of antifibrinolytic agents in post-partum bleeding.

MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, meta Register of Controlled Trials, RHL (WHO Reproductive Health Library), LILACS, African HealthLine, CINAHL, POPLINE, MEDCARIB and ClinicalTrials.gov were searched to November 2008 with no language restrictions. Search terms were available online. Reference lists of relevant trials were searched.

Randomised controlled trials (RCTs) in women with any type of bleeding from the genital tract during the postpartum period that compared anti-fibrinolytic agents (aprotinin, tranexamic acid and epsilon-aminocaproic acid) with placebo or no treatment were eligible for inclusion.

Included trials were of women who had caesarean section delivery (two trials) and spontaneous vaginal delivery (one trial) who were term primiparas and multiparas with singleton pregnancy. The intervention in the included studies was tranexamic acid (0.5g or 1g intravenously) or aminomethylbenzoic (0.5g intravenously) administered with oxytocin. The control was oxytocin with or without methylergometrine, or no treatment. Only studies that used 1g tranexamic acid were included in the meta-analysis. The primary outcome was mortality. Various secondary outcomes were reported.

Two reviewers selected studies for inclusion.

Methodological quality was assessed in terms of allocation concealment according to published criteria. Studies were categorised as A (adequate allocation concealment, methods specified); B (no reporting of allocation concealment or methods other than those specified); and C (inadequate allocation concealment). Use of blinding, randomisation, loss to follow-up and use of intention-to-treat analysis were reported.

The authors did not state how many reviewers assessed validity.

Two reviewers extracted means and standard deviations (SDs) for blood loss. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated for postpartum haemorrhage and adverse reactions. Authors were contacted for further information if necessary.

Means or relative risks and their 95% CIs were pooled in a fixed-effect meta-analysis. Heterogeneity was assessed using the I² statistic and Χ².

Three RCTs were included (n=461, range 100 to 181). Two RCTs scored B for allocation concealment and one scored C. Randomisation method was reported in all trials. There was no blinding in one trial and blinding was not reported in two trials. Participants were followed up for two hours after childbirth in all trials.

The primary outcome of mortality was not reported in any study. Tranexamic acid was associated with a significant reduction in mean blood loss by 92mL (95% CI 76 to 109; three RCTs) compared with control. There was no evidence of heterogeneity. One study reported a lower incidence in postpartum haemorrhage in women who received tranexamic acid compared with control (RR 0.44, 95% CI 0.31 to 0.64).

The most frequently reported adverse event with tranexamic acid was nausea; this was not significant.

There was insufficient evidence from RCTs to confirm or refute a clinically important treatment effect from tranexamic acid in postpartum bleeding.

The research question was supported by clear inclusion criteria. A number of relevant databases were searched in all languages, which reduced the possibility of language bias. Unpublished studies were not sought and so publication bias could not be ruled out. Two reviewers performed data extraction and study selection, which reduced the risk of reviewer error and bias; it was not reported whether similar steps were taken for validity assessment. Validity was assessed; a number of methodological aspects were not reported in the primary studies, which suggested that these studies were of limited quality. Few participant details were provided so it was unclear whether the studies were clinically similar and, therefore, whether pooling was appropriate. Statistical heterogeneity was assessed and not found to be present. In the results, most weighting was on one study, there was only a small number of studies and participants, and controls received oxytocin. The authors' cautious conclusions appeared to reflect the evidence, but given a limited number and poor-quality of studies and potential for bias, the reliability of these conclusions is unclear.

Practice: The authors did not state any implications for practice.

Research: The authors stated that a high-quality randomised controlled trial that compared tranexamic acid to placebo was required to determine whether tranexamic acid improved patient outcome in postpartum bleeding.

Not stated.

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.