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Tranexamic Acid

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Professor Stephen Bernard: Tranexamic Acid.
From CICM ASM PROGRAM 2019

Published in: Health & Medicine
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Tranexamic Acid

  1. 1. TXA in Trauma Stephen Bernard ASM MB BS MD FACEM FCICM FCCM
  2. 2. Myles PS, et al. Tranexamic Acid in Patients Undergoing Coronary-Artery Surgery. N Engl J Med 2017; 376:136-148 • 4631 patients undergoing coronary artery surgery • 100mg/kg IV during first 30 minutes, dose decreased to 50mg/kg after 1526 patients had been enrolled • The POM was a composite of death and thrombotic complications (nonfatal MI, stroke, PE, renal failure, or bowel infarction) within 30 days after surgery. • The POM occurred in 16.7% in the TXA group and 18.1% in the placebo group (p=0.22) • Major haemorrhage or cardiac tamponade leading to reoperation occurred in 1.4% of the patients in the TXA group vs 2.8% of the patients in the placebo group (P=0.001) • Seizures occurred in 0.7% (TXA) vs 0.1% placebo (p=0.002)
  3. 3. WOMAN Trial Collaborators. 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. Lancet 2017; 389:2105-2116. • 2060 women with a clinical diagnosis of post-partum haemorrhage after a vaginal birth (>500mL) or caesarean section (>1L) or CVS instability from 193 hospitals in 21 countries • Given 1 g intravenous TXA or 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 TXA or placebo could be given • Death due to bleeding was significantly reduced in women given tranexamic acid: 1·5% vs 1·9%, (risk ratio 0·81, 95% CI 0·65-1·00; p=0·045)
  4. 4. WOMAN-2 Trial: Clinicaltrials.gov • A randomised, double blind, placebo controlled trial • 10,000 women with moderate or severe anaemia having given birth vaginally • TXA 1gm IV or placebo after cord clamped • Planned to start April 2019 and finish March 2022
  5. 5. Sprigg N, et al. Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage (TICH-2): an international randomised, placebo-controlled, phase 3 superiority trial. Lancet 2018; 391:2107-2115 • 2325 patients with ICH at 124 hospitals in 12 countries. • Participants were randomly assigned (1:1) to receive 1 g intravenous TXA bolus followed by an 8 h infusion of 1 g TXA or a matching placebo, within 8 h of symptom onset. • POM= functional status at day 90, did not differ significantly between the groups • Mortality at 90 days 22% vs 21% (p=0.37)
  6. 6. Sprigg N, et al. Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage (TICH-2): an international randomised, placebo-controlled, phase 3 superiority trial. Lancet 2018; 391:2107-2115 • 2325 patients with ICH at 124 hospitals in 12 countries. • Participants were randomly assigned (1:1) to receive 1 g intravenous TXA bolus followed by an 8 h infusion of 1 g TXA or a matching placebo, within 8 h of symptom onset. • POM= functional status at day 90, did not differ significantly between the groups • Mortality at 90 days 22% vs 21% (p=0.37) • “Larger randomised trials are needed to confirm or refute a clinically significant treatment effect.”
  7. 7. Lancet 2010; 376:23-32
  8. 8. • 20,211 trauma patients within 8 hours of injury and SBP<90 or HR>110 or “at risk of significant haemorrhage” in ED given loading dose 1g TXA IV over 10 mins then IV infusion 1g over 8 hours in • 274 hospitals in 40 countries • POM was death in hospital within 4 weeks • TXA significantly reduced all-cause mortality (14.5% TXA vs 16.0% placebo: p=0.0035) • TXA reduced risk of death due to bleeding (4.9% TXA vs 5.7% placebo: p=0.0077)
  9. 9. BUT • 98% of patients in CRASH-2 were treated in “developing” countries (India 4768, Columbia 2940, Egypt 2234, Georgia 1783, Ecuador 1198, Indonesia 706, Cuba 575, Malaysia 216) compared with UK 135, Australia 17, Canada 2 • Inclusion was SBP<90 or HR>110 or “at risk of significant haemorrhage” and only 50% received a blood transfusion with median 3 units • Prehospital TXA and likely bleeding would be better ?
  10. 10. Morrison JJ et al. Association of Cryoprecipitate and Tranexamic Acid With Improved Survival Following Wartime Injury: Findings From the MATTERs II Study. JAMA Surg 2013; 148:218-225 • 1332 patients who required 1 U or more PRBC and who received tranexamic acid (n = 148), cryoprecipitate (n = 168), tranexamic acid/cryoprecipitate (n = 258), and no tranexamic acid/cryoprecipitate (n = 758).
  11. 11. Boudreau RM, et al: Prehospital Tranexamic Acid Administration During Aeromedical Transport After Injury. J Surg Res 2019; 233:132-138 • 116 patients (62 prehospital versus 54 ED) observational . • Prehospital TXA patients were more likely to have sustained blunt injury (76% prehospital versus 46% ED, P = 0.002). • There were no differences between groups in injury severity score or initial vital signs. There were no differences in complication rates or mortality. • Patients receiving TXA had higher rates of venous thromboembolic events (8.1% in prehospital and 18.5% given TXA in ED) than the overall trauma population (2.1%, P < 0.001)
  12. 12. • CRASH-3 RCT of TXA in TBI  12,735 patients  Sites in Europe, Asia, South America  GCS < 12 or traumatic ICH  In ED: Ig TXA bolus and 1gm over 8 hours  Recruiting closed January 31st 2019  Results late 2019
  13. 13. Clinicaltrials.gov: 31 Phase 3 studies of TXA – actively recruiting: • PATCH • Non-trauma  Bariatric surgery  AAA rupture  Chronic subdural  Orthopedic surgery  Liver surgery  Face surgery  Spine surgery
  14. 14. Pre-hospital Anti-fibrinolytics for Traumatic Coagulopathy and Haemorrhage (PATCH) Study Lead Investigators: Russell Gruen, Stephen Bernard, Colin McArthur, Michael Reade, Dev Mitra, Dashiell Gantner, Brian Burns, Stephen Rashford, Tony Smith, Stefan Mazur Coordinating Centre: ANZICS-RC, Monash University Melbourne, Australia Website: www.patchtrauma.org Email: info@patchtrauma.org
  15. 15. • 1186 patients >18 years with suspected traumatic bleeding pre-hospital within 3 hours of injury using COAST score >2 • Double blind RCT • Allocated to TXA 1gm IV bolus or placebo and then in ED, commence matching TXA 1gm or placebo in 1L normal saline over 8 hours • POM is good functional recovery (GOSe 5-8) at 6 months • Secondary outcome measures are PE, DVT , blood products, surgery, mortality at discharge • Funded by NHMRC ($2M), ICF (TXA levels), NZ MRC
  16. 16. COAST SCORE - VARIABLE VALUE SCORE Entrapment (i.e., in a vehicle) ☐ YES ☐ 1 Systolic Blood Pressure (mmHg) ☐ 90 – 100 ☐ <90 ☐ 1 ☐ 2 Temperature (°C) ☐ 32 – 35 ☐ <32 ☐ 1 ☐ 2 Major chest injury likely to require intervention (e.g. decompression, chest tube) ☐ YES ☐ 1 Likely intra-abdominal or pelvic injury ☐ YES ☐ 1 Total score:
  17. 17. 0.00 296.00 592.00 888.00 1184.00 PATCH Recruitment Recruitment Average Projection
  18. 18. Challenges • Establishing research by trauma services in some Australian major trauma hospitals • Prehospital enrolment in challenging trauma cases • Completing the 8 hour infusion in OT and ICU • Bloods as per trial protocol (initial and 8 hour) • Delayed consent • Open label TXA +/- ROTEMS/ TEGs • 6 month follow-up
  19. 19. SUMMARY- SHOULD I GIVE TXA? YES! • CAGS • PPH • Joint replacement • Trauma in a remote setting MAYBE? • Major Trauma Service with massive transfusion protocol • Cardiac Valve surgery NO! • Spontaneous Intracranial bleed
  20. 20. Thank you! s.bernard@alfred.org.au @AmbVicMedic

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