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

Editorial: Trends in gynaecologic endoscopy in Nigeria

No Abstrac

Displaced intra-uterine contraceptive device causing severe menorrhagia

The intrauterine contraceptive device (IUCD) is a common method of contraception in developing countries. Expulsion/displacement is a common complication of its use, occurring in 2-8 % of users per 100 women years. Two cases of menorrhagia resulting from displacement of Copper-T-380 IUCD to the cervical canal were presented. The diagnosis was made by simple gentle speculum examination of the vagina and confirmed in one case with ultrasonography. The IUCD was pulled out with an artery or sponge forceps and the bleeding stopped. Awareness of this possible complication and simple speculum examination in any woman wearing an IUCD and presenting with vaginal bleeding or menorrhagia is advocated to avert undue morbidity. Keywords: IUCD, displacement, expulsion, menorrhagia Tropical Journal of Obstetrics and Gynaecology Vol. 23(1) 2006: 70-7

Endometriosis presenting as pleural effusion and haemoperitoneum: case report and a review of the literature

A case of endometriosis presenting as haemorrhagic pleural effusion and ascites in a 40 year old multiparous woman is described. Her main clinical features were left groin swelling 12 years prior to this presentation which was confirmed at histology (after excision) to be endometriosis; secondary infertility, peri-umbilical nodule with cyclic pain especially during the menstrual flow; secondary dysmenorrhoea, dyspareunia, irregular menses, inter-menstrual bleeding, dyspnoea and abdominal swelling. Investigations revealed pleural effusion on chest X-ray and a complex pelvic-abdominal mass with ascites on ultrasonography. She was managed with danazol, thoracotomy and, eventually, laparotomy. Subtotal hysterectomy with bilateral salpingoophorectomy was performed and histological examination of the tissues confirmed endometriosis and adenomyosis. Keywords: endometriosis, pleural effusion, ascites Tropical Journal of Obstetrics and Gynaecology Vol. 23(1) 2006: 77-7

Intravenous versus intramuscular oxytocin injection for preventing uterine atonic primary postpartum haemorrhage in third stage of labour: A double-blind randomised controlled trial

Objectives: To compare the efficacy and safety of intravenous and intramuscular oxytocin in preventing atonic primary postpartum haemorrhage in the third stage of labour. Methods: A double-blind randomised clinical study on consenting women without risk factors for primary postpartum haemorrhage in labour at term. Two hundred and thirty-two women were randomly allotted into intravenous ( n  = 115) and intramuscular ( n  = 117) oxytocin groups in the active management of the third stage of labour. All participants received 10 IU of oxytocin, either IV or IM, and 1 ml of water for injection as a placebo via a route alternate to that of administration of oxytocin within 1 min of the baby’s delivery. The primary outcome measures were mean postpartum blood loss and haematocrit change. Trial Registration No.: PACTR201902721929705. Results: The baseline socio-demographic and clinical characteristics were similar between the two groups ( p  > 0.05). There was no statistically significant difference between the two groups with regards to the mean postpartum blood loss (254.17 ± 34.85 ml versus 249.4 ± 39.88 ml; p  = 0.210), haematocrit change (2.4 (0.8%) versus 2.1 (0.6%); p  = 0.412) or adverse effects ( p  > 0.05). However, the use of additional uterotonics was significantly higher in the intravenous group (25 (21.73%) versus 17 (14.53%); p  = 0.032). Conclusion: Although oxytocin in both study groups showed similar efficacy in terms of preventing atonic primary postpartum haemorrhage, participants who received intravenous oxytocin were more likely to require additional uterotonics to reduce their likelihood of having an atonic primary postpartum haemorrhage. However, both routes have similar side effect profiles