Effect 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

Background Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage. Methods In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283. Findings Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group. Interpretation Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset. Funding London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation

GENITO-URINARY FISTULA: A MAJOR MORBIDITY IN DEVELOPING COUNTRIES

Background: Uro-genital fistulas, majority of which are vesico-vaginal fistulas (VVF), are a great challenge for women in developing countries. It is commonly caused by prolong obstructed labour and is one of the worst complications of child birth and poor obstetric care. The objective of this descriptive study was to review the cases of genitourinary fistulae so as to understand the magnitude of the problem and its aetiology and to share our experience of surgical repair with other specialists in this field. The study was conducted at Gynaecological Unit-II, Liaquat University Hospital Hyderabad, Pakistan from June 1996 to December 2007. Methods: The case records of all patients admitted and managed during study period were reviewed. The information regarding characteristics, risk factors and surgical management was collected. The data was analysed by SPSS and mean, range, standard deviation and percentage were calculated. Results: During the study period, 278 patients with genitourinary fistulae were admitted and managed. The mean age of patients with urinary fistulae was 31.5±7.5 years, parity was 4.2±2.8, and duration of labour was 38.4±6.5 hours. The duration of fistulae ranged from 1 day to 25 years. Obstructed labour 246 (88.4%) was the most common cause of urinary fistulae, followed by gynaecological surgeries mainly hysterectomies 26 (9.35%). The most common type of urinary fistula was vesico-vaginal fistula (VVF) 250 (89.9%). A total of 268 underwent surgery. Almost all 261 (97.3%) urinary fistulae were repaired transvaginally except patients with ureterovaginal and vesico-uterine fistulae. The most common surgical procedure used was layered closure. Martius graft was used in 3 (1.1%) patients, who required creation of new urethra. The success rate following first, second and third attempt was 85%, 91% and 96% respectively. Conclusion: Urogenital fistulae are rarity in developed world, but are frequently encountered problem in developing countries like Pakistan, often resulting from prolonged obstructed labour due to poor obstetric care. Utilising basic principles of surgery, all types of urinary fistulae can be repaired