This review concluded that tranexamic acid appeared to reduce blood loss and the need for blood transfusions after delivery during caesarean sections and vaginal deliveries and appeared safe and effective for prevention and management of bleeding during pregnancy. Methodological limitations of the included studies and discrepancies in the analyses mean that the findings of this review may not be reliable.

To evaluate the use, safety and efficacy of tranexamic acid for management of haemorrhage during pregnancy and for prevention and treatment of postpartum haemorrhage.

MEDLINE, EMBASE, CINAHL, SCOPUS, The Cochrane Library and DARE were searched up to June 2010 for studies in any language. Search terms were reported. Additional searches were carried out to identify published and unpublished studies from relevant conferences, scientific meetings and reference lists of retrieved studies.

Randomised controlled trials (RCTs), non-randomised observational studies, case series and case reports that reported on tranexamic acid for the management of obstetric haemorrhage during pregnancy and post-partum (up to six months) were included in the review. Relevant outcomes were platelet count, quantity of blood loss, adverse effects, response-outcome measures and need for additional treatments.

Included studies assessed doses of tranexamic acid that ranged from 500mg to 6g. Treatment duration ranged from over five minutes to 64 days. Treatment was administered from five weeks to 40 weeks gestation (where reported). Half of the included RCTs were multicentre studies and half were single centre. Comparisons included alternative doses of tranexamic acid and placebo. Participants ranged in age from 24.3 to 32.1 years (where reported). RCTs were published between 2001 to 2010. Non-randomised observational studies were published between 1980 to 2009 and included participants who ranged in age from 25 to 30 years (where reported). Most studies were of antepartum bleeding. Case reports were published between 1976 and 2010 and included participants who ranged in age from 16 to 39 years. Most reports were of management of postpartum haemorrhage; other causes included haematological disorders. Studies were published in English, Chinese, Russian, Danish and Polish. Most studies were carried out in Europe; others were in Asia and one was in Oceania.

Two reviewers assessed the studies for inclusion. Any disagreements were resolved through consensus or by the involvement of a third reviewer.

The methodological quality of included RCTs was assessed according to criteria on allocation concealment (as described by Schulz; graded A to C), adequacy of randomisation, use of blinding, use of placebo and intention-to-treat analyses. The methodological quality of the observational studies, case series and case reports was not assessed formally, but study design was graded using Scottish Intercollegiate Guidelines Network (SIGN) evidence levels.

The authors did not state how many reviewers performed the validity assessment.

The mean and standard deviation of continuous outcomes such as blood loss were extracted. Differences in means were calculated with 95% confidence intervals (CIs); p-values were reported where available. Dichotomous data were reported as odds ratios (ORs) and 95% CIs.

The authors did not state how many reviewers performed the data extraction.

The studies were grouped according to aim and patient population and pooled according to outcome using a random-effects or fixed-effect model (dependent on the level of statistical heterogeneity detected). Statistical heterogeneity was assessed using the I² statistic. Pooled mean differences with 95% CIs were reported.

The review included total of 3,271 patients enrolled in: six RCTs (994 patients), seven non-randomised observational studies (409 patients) and 22 case reports (numbers differed between the text and data tables). None of the RCTs reported adequate allocation concealment; all reported adequate randomisation, but none were blinded or reported intention-to-treat data. One of the seven non-RCT observational studies was awarded an evidence grade of 3, three were awarded a 2+, and two studies a 2-. One study was not awarded an evidence level.

Three RCTs that assessed the effects of tranexamic acid administration prior to caesarean section all reported that blood loss was significantly reduced for tranexamic acid in comparison with placebo. Studies of the early management of postpartum haemorrhage after vaginal delivery reported a lower blood loss (two RCTs) associated with tranexamic acid and a shorter duration of bleeding (one RCT) in comparison with placebo. One RCT to arrest bleeding in women with a history of miscarriage reported a significant reduction in the duration of bleeding episodes (p<0.001) in comparison with placebo. There was no significant reduction in pooled postpartum blood loss compared with placebo when tranexamic acid was given prior to caesarean section (three RCTs). This meta-analysis was associated with a significant degree of statistical heterogeneity (I²=98.7%). Adverse events reported in the RCTs included transient visual and digestive effects (one RCT), transient mild adverse events (one RCT) and nausea (one RCT). Three RCTs reported no significant maternal or neonatal adverse effects.

The review reported data for the included non-randomised observational studies and case reports. In these studies tranexamic acid was found to show beneficial effects in preventing and treating bleeding. Adverse events reported in the studies included two cases of pulmonary embolism; however, the possible involvement of tranexamic acid was not proven.

Tranexamic acid appeared to reduce blood loss after delivery during caesarean sections and vaginal deliveries and reduce the need for blood transfusions. Tranexamic acid appeared safe and effective for the prevention and management of bleeding during pregnancy.

This review answered a clearly defined research question using a broad range of study designs. Several relevant resources were searched for published and unpublished studies without language restrictions, which reduced risks of publication and language biases. Attempts were made to reduce reviewer error and bias when selecting studies for inclusion; it was unclear whether similar precautions were taken when extracting the study data and assessing the methodological quality of the studies.

The methodological quality of the studies was assessed using relevant criteria for the assessment of RCTs; other observational studies were awarded a level of evidence grade dependent on their design type rather than a formal assessment of their methodological quality. The quality of the included studies (including RCTs) showed risks of bias within the studies that suggested the data may not have been reliable in some cases. Clinical variations between studies limited the statistical pooling of the RCTs. Where pooling was possible, this involved only a small number of the studies and was subject to a significant level of statistical heterogeneity. There appeared to be discrepancies between data reported in the text and those reported in the tables and figures.

Given the methodological limitations of the included studies and the pooled analysis, the findings of this review may not be reliable and the authors are justified in recommending the need for further research.

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

Research: The authors stated a need for further large well-designed high-quality clinical trials of tranexamic acid for obstetric haemorrhage during pregnancy and the post-partum period.

None 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.