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 riskof 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