No effect of tranexamic acid on platelet function and thrombin generation (ETAPlaT) in postpartum haemorrhage: A randomised placebo-controlled trial.

Abstract

Background: Postpartum hemorrhage (PPH) is a leading cause of maternal mortality and morbidity. The WOMAN trial showed that tranexamic acid (TXA) reduces death due to bleeding in women with PPH. To determine whether TXA has pro-thrombotic effects in women with PPH, we measured endogenous thrombin potential (ETP), coagulation factors V, VIII, von Willebrand (vW), fibrinogen, D-Dimers and platelet function. Methods: We conducted a sub-study within the WOMAN trial, an international randomized, parallel-group, double blind, placebo-controlled trial. Women with primary PPH were randomly allocated to receive 1 gram of tranexamic acid or matching placebo. Baseline blood samples were collected just prior to the first dose and a follow up sample was collected 30±15 minutes afterwards. We compared before and after changes in coagulation parameters between treatment groups using repeated measurement ANOVA. Change in ETP was the primary outcome. We did an intention-to-treat analysis using ANCOVA with adjustment for baseline and the time interval between the blood samples. Findings: A total of 187 patients were randomized to receive TXA (n=93) or matching placebo (n=94). Six patients were excluded due to incomplete data. The reduction in ETP from baseline to follow up was 43.2 nM*min (95%CI,-16.6 to 103.1) in the TXA group and 4.6 nM*min (95%CI,-51.4 to 60.6) in the placebo group. The difference was not statistically significant (95%CI,-42.9 to 120). There were no significant effects of TXA treatment on any other parameters (ADPtest, TRAPtest, coagulation factors activity, fibrinogen levels, D-Dimer level). Conclusion: We found no evidence that tranexamic acid treatment for PPH has substantial pro-coagulant effects. However, larger studies are needed has substantial pro-coagulant effects. However, larger studies are needed to confirm or refute more modest effects. Trial registration: ISRCTN76912190 (initially registered 10/12/2008, WOMAN-ETAPlat included on 28/10/2013) and NCT00872469 (initially registered 31/03/2009, WOMAN-ETAPlat included on 28/10/2013).