Haleema Shakur-Still, Ian Roberts, Stanislas Grassin-Delyle, Rizwana Chaudhri, Amber Geer, Monica Arribas, Elodie Lamy, Raoul Mansukhani, Mwansa Ketty Lubeya, Kiran Javaid, Aasia Kayani, Naila Israr, Syeda Batool Mazhar, Saïk Urien, Naïm Bouazza, Frantz Foissac, Danielle Prowse, Laura Carrington, Collette Barrow, Julio Gil Onandia, Eni Balogun
Haleema Shakur-Still and Ian Roberts and Bukola Fawole and Modupe Kuti and Oladapo O Olayemi and Adenike Bello and Sumaya Huque and Olayinka Ogunbode and Taiwo Kotila and Chris Aimakhu and Olujide A Okunade and Tolulase Olutogun and Cecilia O Adetayo and Kastriot Dallaku and Ulrich Mansmann and Beverley J Hunt and Tracey Pepple and Eni Balogun
Background: Postpartum haemorrhage (PPH) is a leading cause of maternal death. The WOMAN trial showed that tranexamic acid (TXA) reduces death due to bleeding in women with PPH. We evaluated the effect of TXA on fibrinolysis and coagulation in a sample of WOMAN trial participants.
Methods: Adult women with a clinical diagnosis of PPH were randomised to receive 1 g TXA or matching placebo in the WOMAN trial. Participants in the WOMAN trial at University College Hospital (Ibadan, Nigeria) also had venous blood taken just before administration of the first dose of trial treatment and again 30 (±15) min after the first dose (the ETAC study). We aimed to determine the effects of TXA on fibrinolysis (D-dimer and rotational thromboelastometry maximum clot lysis (ML)) and coagulation (international normalized ratio and clot amplitude at 5 min). We compared outcomes in women receiving TXA and placebo using linear regression, adjusting for baseline measurements.
Results: Women (n=167) were randomised to receive TXA (n=83) or matching placebo (n=84). Due to missing data, seven women were excluded from analysis. The mean (SD) D-dimer concentration was 7.1 (7.0) mg/l in TXA-treated women and 9.6 (8.6) mg/l in placebo-treated women (p=0.09). After adjusting for baseline, the D-dimer concentration was 2.16 mg/l lower in TXA-treated women (-2.16, 95% CI -4.31 to 0.00, p=0.05). There was no significant difference in ML between TXA- and placebo-treated women (12.3% (18.4) and 10.7% (12.6), respectively; p=0.52) and no significant difference after adjusting for baseline ML (1.02, 95% CI -3.72 to 5.77, p=0.67). There were no significant effects of TXA on any other parameters.
Conclusion: TXA treatment was associated with reduced D-dimer levels but had no apparent effects on thromboelastometry parameters or coagulation tests.
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 15000 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 15000 to 20000 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.
Katharine Ker, Ian Roberts, Rizwana Chaudhri, Bukola Fawole, Danielle Beaumont, Eni Balogun, Danielle Prowse, Tracey Pepple, Kiran Javaid, Aasia Kayani, Sabaratnam Arulkumaran, Imelda Bates & Haleema Shakur-Still on behalf of the WOMAN-2 trial collaborators
Angèle Gayet-Ageron, David Prieto-Merino, Katharine Ker, Haleema Shakur, François-Xavier Ageron, Ian Roberts, for the Antifibrinolytic
Amy Brenner, Ian Roberts, Eni Balogun, Folasade Adenike Bello, Rizwana Chaudhri, Charlotte Fleming, Kiran Javaid, Aasia Kayani, Mwansa Ketty Lubeya, Raoul Mansukhani, Oladapo Olayemi, Danielle Prowse, Bellington Vwalika & Haleema Shakur-Still
Roberto Picetti, Lori Miller , Haleema Shakur-Still , Tracey Pepple , Danielle Beaumont , Eni Balogun, Etienne Asonganyi , Rizwana Chaudhri , Mohamed El-Sheikh , Bellington Vwalika, Sabaratnam Arulkumaran, Ian Roberts and on behalf of the WOMAN trial collaborators
David A. KolinID, Haleema Shakur-Still , Adenike Bello, Rizwana Chaudhri , Imelda Bates, Ian Roberts
Amy Brenner1* , Haleema Shakur-Still1 , Rizwana Chaudhri2 , Bukola Fawole3 , Sabaratnam Arulkumaran4 , Ian Roberts1 and on behalf of the WOMAN Trial Collaborators