Don’t Forget TXA in the Trauma Bay

Author: Michael  A. Schwarz, Pharm.D., R.Ph.

Tranexamic Acid (TXA)

• Tranexamic Acid (TXA) is a competitive inhibitor of plasminogen activation to plasmin and a noncompetitive inhibitor of plasmin, which produces antifibrinolytic effects and stabilizes clot structure.

• Mayo Clinic TXA protocol for Trauma : TXA is indicated for any acutely injured adult presenting within 3 hours of trauma who is meeting criteria for mass transfusion (2 of the following: Single SBP ≤ 90 mmHg, Single HR ≥ 120 bpm, Lactate ≥ 5 mmol/L, INR ≥ 1.5)
  • Tranexamic Acid (TXA) 1 gram IV Loading Dose over 10 minutes, immediately followed by an infusion of 1 gram over 8 hours.
  • TXA Exclusion Criteria:
    • < 18 years old
    • > 3 hours from injury
    • Current Anticoagulation (warfarin, heparin, LMWH, dabigatran, rivaroxaban, apixaban, etc.)
    • Known Thromboembolic Disease History (DVT, PE, ACS)
    • Evidence of clotting (DVT, PE, embolic stroke)
    • History of retinal vein or artery occlusion
    • Administration of PCCs, Factor VIIa

Studies Supporting Mayo TXA Protocol in Trauma:

• CRASH-2 (Lancet 2010): Prospective, randomized control trial with 20,211 patients in 40 different countries. Patients presenting within 8 hours of injury who were determined by their provider to be at significant risk of bleeding were randomized to receive TXA (n= 10,096) or placebo (n= 10,115). TXA dosing 1 gram over 10 minutes, then 1 gram over 8 hours infusion
  • RESULTS:
    • TXA significantly reduced all-cause mortality from 16% to 14.5% (RR 0.91, 95% CI 0.85-0.97; p = 0.0035)
    • TXA significantly reduced death due to bleeding from 5.7% to 4.9% (RR 0.85, CI 0.76-0.96; p = 0.0077)
  • CONCLUSION:
    • TXA shows reduces all-cause mortality in trauma patients at significant risk of bleeding

• CRASH-2: Timing of TXA Dosing (Lancet 2011): Retrospective analysis of CRASH-2 trial to determine if early timing of TXA from injury improves outcomes
  • RESULTS:
    • TXA ≤ 1 hour from injury reduced risk of death due to bleeding from 7.7% to 5.3%
    • TXA between 1-3 hours from injury reduced risk of death due to bleeding from 6.1% to 4.8%
    • TXA > 3 hours from injury increased risk of death due to bleeding 3.1% to 4.4%
  • CONCLUSION:
    • TXA is beneficial at reducing all-cause mortality in patients with significant risk of bleeding if given within the first 3 hours of a traumatic injury

• MATTERs (JAMA – 2012): Retrospective observational study of military combat injuries in Afghanistan presenting to a surgical center at Camp Bastion. Included were injuries requiring ≥1 unit PRBC and a subset group that received ≥ 10 units PRBC. 896 combat injuries qualified and 293 received TXA (1 gram IV bolus, with discretional repeat)
  • RESULTS:
    • Main Group (≥ 1 PRBC) Mortality: non-TXA 23.9% vs TXA 17.4% (P=0.03)
    • Subset Group (≥ 10 PRBC) Mortality: non-TXA 28.1% vs TXA 14.4% (P <.003)
  •  CONCLUSION:
    • The largest benefit with TXA was seen in the most severe combat injuries which required massive transfusion

 References:

• Effects of Tranexamic Acid on Death, Vascular Occlusive Events, and Blood Transfusion in Trauma Patients with Significant Haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet 2010; 376:23-32
• The Importance of Early Treatment with Tranexamic Acid in Bleeding Trauma Patients: an exploratory analysis of the CRASH-2 Randomised Controlled Trial Lancet 2011; 377:1096-101
• Morrison J et al. Military Application of Tranexamic Acid in Trauma Emergency Resuscitation Study. JAMA 2012; 113-119
• http://mayoweb.mayo.edu/traumacenter/documents/TranexamicAcidUse.pdf
• Photo from: http://www.lshtm.ac.uk/newsevents/news/2011/tran_man.html