Journal Jam 18 The Evidence for TXA – Should Tranexamic Acid Be Routine Therapy in the Bleeding Patient?

TXA has been widely adopted as an effective drug for improving outcomes of patients who are bleeding from a variety of sources, even though many of the trials' conclusions are contentious. One of the major concepts we have discussed on the Journal Jam Podcast is that prior probability matters. When assessing a trial, one's interpretation is often shaped by the science that is already available. So when trying to determine how to interpret a somewhat controversial study like CRASH-3, it is really helpful to take a deep dive into all the available evidence for TXA. This will help us decide when to use TXA in the ED and to gain a broad understanding of this drug. That is our goal here. With the help of a special guest, EBM guru Dr. Ken Milne of the The SGEM, Anton and Justin look at all the various potential indications for TXA and review the available evidence. Should we be using TXA for epistaxis, postpartum hemorrhage, hyphema or hemoptysis? Is it a miracle drug that stops all bleeding? Or has it been drastically overhyped? Was CRASH-2 enough to be definitive, or does the classic EBM mantra of  "we need more studies" remain true?... Podcast production by Justin Morgenstern and Anton Helman. Podcast editing and sound design by Anton Helman. Blog summary by Anton Helman, June 2021. Cite this podcast as: Helman, A. Morgenstern, J. Milne, K. Journal Jam 18 - The Evidence for TXA - Should Tranexamic Acid Be Routine For The Bleeding Patient. Emergency Medicine Cases. June, 2021. https://emergencymedicinecases.com/evidence-txa-tranexamic-acid-bleeding. Accessed [date] Perioperative TXA - tranexamic acid to reduce bleeding, transfusions and mortality associated with surgery Cochrane review 2011 [1] 65 trials with 4800 patients of TXA in the perioperative period TXA reduced the need for blood transfusion by 18% TXA did not reduce the total volume of blood being transfused Post-operative blood loss was reduced by an average of 247 mL There was no difference in mortality, reoperation for bleeding, MI, stroke or thromboembolic phenomena 250 small RCTs, each with only approximately 100 patients, show a consistent signal that perioperative blood loss is reduced, but no patient-oriented outcome benefit and no change in mortality.   TXA for GI bleeds - The HALT-IT trial Cochrane review 2014 [2] 8 low quality small RCTs totalling only 851 patients Statistically significant reduction in mortality and need for surgery with TXA, but no difference in mortality or need for surgery when the large number of lost patients were taken into account No statistically significant reduction in rebleeding or transfusion requirements or thrombotic events HALT-IT trial [3] HALT IT was a pragmatic, international, multi-center, placebo-controlled RCT with 12,009 patients with GI bleeds (90% upper GI). There was no difference in all cause mortality, death due to bleeding, rebleeding, surgery, endoscopy, need for transfusion, or total blood products transfused between the TXA group and placebo group. The only statistically significant difference was an increase in venous thromboembolic events from 0.4% to 0.8%.   TXA for postpartum hemorrhage - WOMAN trial, TRAAP trial and TRAAP-2 trial Two large RCTS looked at TXA for prevention of postpartum hemorrhage, the TRAAP trial [4] and the TRAAP 2 trial [5]. In the TRAAP trial there was no difference in the primary outcome of blood loss of at least 500 mL. In the TRAAP-2 trial there was a statistically significant reduction in postpartum hemorrhage, defined as estimated blood loss > 1L or need for transfusion within 2 days - 27% with TXA versus 36% with placebo. However for single outcomes there was only a 30 mL difference in bleeding, no difference in transfusion, no difference in hemoglobin level,