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

Pattern of Ureteric Pathology Presenting to a Fistula Centre in Western Kenya

Background. Ureteric pathology arises from surgical misadventures, trauma, and congenital anomalies. Early detection and treatment is of the essence. Objectives. To determine the types/etiology and outcome of ureteric pathology presenting to Gynocare Fistula Centre, Eldoret, Kenya. Methods. Descriptive retrospective study that evaluated patients presenting with ureteric pathology at Gynocare between 1st January 2012 and 31st December 2016. We pulled out patient charts and extracted and analyzed relevant data using STATA 13E statistical software. Results. We analyzed 33 charts, and their age ranged from 10 to 58 years. Annual proportion for 2012, 2013, 2014, 2015, and 2016 was 2.5%, 2.8%, 1.2%, 1.4%, and 3.0% respectively among all the fistula patients treated in the hospital. All the patients presented with urinary incontinence, and 7 (21.2%) had flank pain. Iatrogenic injuries contributed 84.8% (28), and 3 (9.1%) were congenital while trauma and infection had 1 each. Of those resulting from surgical misadventures, 17 (60.7%) were from obstetric while 11 (39.2%) were from gynecological surgery. All the injuries were in the distal third of the ureter; 5 were bilateral; and 11 were left sided while 17 were right-sided. Repair and/or reimplantation was successful in 31 (93.93%) of the patients. Conclusion. Highest proportion of ureteric pathologies was accounted for by iatrogenic causes and surgical repair and/or reimplantation has a high success rate