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

HEPATO-PROTECTIVE ROLE OF THE AQUEOUS AND N-HEXANE EXTRACTS OF NIGELLA SATIVA LINN. IN EXPERIMENTAL LIVER DAMAGE IN RATS

Objective: Liver disease is associated with the formation of oxygen derived free radicals. Reactive oxygen species (ROS) as well as nitrogen species are responsible for nuclear DNA fragmentation and cell death. Active principle of thymoquinone (TQ) of Nigella sativa acts as a scavenger of superoxide anion. Current study was conducted to evaluate the hepatoprotective effect of Nigella sativa on rats. Methods: The study was carried out at prime postgraduate medical University of Bangladesh. Liver damage and oxidative stress were evaluated by measuring serum alanine amino transferase (ALT), hepatic malondialdehyde (MDA) and hepatic Glutathione (GSH) levels. Aqueous extract of Nigella sativa and n-hexane extract of Nigella sativa were administered orally into two groups' of rats through intra-gastric tube for 28 days. Both the groups received paracetamol intraperitoneally on day 28th and were sacrificed on day 30th. Subsequently, the following parameters were studied: Serum ALT, hepatic MDA, and hepatic GSH. Results: Hepatic damage was evaluated by significant increases in serum ALT (p<0.001) and hepatic MDA (p<0.001) concentration with depleted hepatic GSH (p<0.001) in paracetamol treated group. Pre-treated with aqueous extract of Nigella sativa significantly reduced serum ALT (p<0.001) and hepatic MDA (p<0.001) levels and also significantly associated with the increase in hepatic GSH (p<0.01). Pretreatment with n-hexane extracts of Nigella sativa decreased serum ALT (p<0.001), hepatic MDA (p<0.001) and increased hepatic GSH (p<0.001). Conclusion: Hepatoprotective properties of Nigella sativa in liver damage of experimental rats by reducing oxidative stress is evident. Protection afforded by the n-hexane extract of Nigella Sativa in pre-treated group has also been validated. KEY WORDS: Hepatoprotective, Liver-damage, Nigella sativa Linn