(December 2022)

The antifibrinolytic agent tranexamic acid (TXA) is a synthetic lysin derivative that binds plasminogen and plasmin, blocking their interaction with fibrin (4). It is indicated extensively in the ED for a variety of bleeding scenarios. 

• The most validated usage is in patients with acute trauma with a suspected severe hemorrhage (1, 3, 5, 7, 12). Currently it is an established component of “damage control resuscitation” (3, 5, 9). 

• All-cause mortality reduction was proven by the game-changer CRASH-2 trial –a strong double-blind RCT that compared TXA versus a placebo in trauma, based on the uncertainty principle (attending physician not being sure if TXA was beneficial or not)(1)–. Afterwards other studies have documented improved survival rates (3, 7, 11).

• Later on TXA was studied in acute traumatic brain injury (TBI). It was found to have a limited potential benefit in reducing head injury associated deaths in mild to moderate TBI (6). Nonetheless TXA was recently indicated and included for TBI in combat medical guidelines (8, 9).

Adult dose for trauma with risk of significant hemorrhage (1)

1gr in 10 min + 1gr in 8 hrs IV.

Adult dose for trauma with risk of significant haemorrhage (1)

• 1gr in 10 min + 1gr in 8 hrs IV.

• Undifferentiated Trauma; based on CRASH-2 criteria: “adult trauma patients with significant hemorrhage (systolic blood pressure <90 mm Hg or heart rate >110 beats per min, or both), or who were considered to be at risk of significant hemorrhage” (1).

• Traumatic Brain Injury; based on CRASH-3 criteria: "adults with TBI who were within 3 h of injury, had a Glasgow Coma Scale (GCS) score of 12 or lower or any intracranial bleeding on CT scan" (6). Potential benefit in mild to moderate TBI (Glasgow Coma Scale 9 to 15).

• Some experts initiate TXA if the ABC score is ≥2 (ABC Score for Massive Transfusion - MDCalc), when massive transfusion is likely required. 

• Best time is early: <1 hour of injury.

• TXA should be administered early within 3 hours from injury, with the most beneficial results when administered in the first hour (2).

From a physiopathological point of view, TXA should be administered when fibrinolytic activity is augmented, which can objectively be measured with viscoelastic assays like thromboelastography (TEG)(10). Interestingly, recent studies show that an early administration of TXA prevents development of a hyperfibrinolytic state which supports its usage not only in severely injured patients (7, 12, 13). 

Remarkable compendiums and analyses of the trial can be found at The Bottom Line and at The NNT. 

1. CRASH-2 trial collaborators, Shakur H, Roberts I, et al. 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(9734):23-32. doi:10.1016/S0140-6736(10)60835-5
   The Lancet (Open Access)

2. CRASH-2 collaborators, Roberts I, Shakur H, et al. 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(9771):1096-1101.e11012. doi:10.1016/S0140-6736(11)60278-X
   Pubmed

3. Morrison JJ, Dubose JJ, Rasmussen TE, Midwinter MJ. Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study. Arch Surg. 2012;147(2):113-119. doi:10.1001/archsurg.2011.287
   Pubmed

4. Brunton LL, Hilal-Dandan R, Knollmann BC. Goodman & Gilman's: The Pharmacological Basis of Therapeutics. 13th edition. McGraw Hill; 2017.
   McGraw-Hill

5. Cap AP, Pidcoke HF, Spinella P, et al. Damage Control Resuscitation. Mil Med. 2018;183(suppl_2):36-43. doi:10.1093/milmed/usy112
   Pubmed

6. CRASH-3 trial collaborators. Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): a randomised, placebo-controlled trial [published correction appears in Lancet. 2019 Nov 9;394(10210):1712]. Lancet. 2019;394(10210):1713-1723. doi:10.1016/S0140-6736(19)32233-0
   Pubmed

7. Ageron FX, Gayet-Ageron A, Ker K, et al. Effect of tranexamic acid by baseline risk of death in acute bleeding patients: a meta-analysis of individual patient-level data from 28 333 patients. Br J Anaesth. 2020;124(6):676-683. doi:10.1016/j.bja.2020.01.020
   Pubmed

8. Drew B, Auten JD, Cap AP, et al. The Use of Tranexamic Acid in Tactical Combat Casualty Care: TCCC Proposed Change 20-02. J Spec Oper Med. 2020;20(3):36-43. doi:10.55460/ZWV3-5CBW
   Pubmed

9. Tactical Combat Casualty Care (TCCC) Guidelines for Medical Personnel 15 December 2021. J Spec Oper Med. 2022;22(1):11-17. doi:10.55460/ETZI-SI9T
   Pubmed

10. Moore EE, Moore HB, Kornblith LZ, et al. Trauma-induced coagulopathy [published correction appears in Nat Rev Dis Primers. 2022 Apr 22;8(1):25]. Nat Rev Dis Primers. 2021;7(1):30. Published 2021 Apr 29. doi:10.1038/s41572-021-00264-3
    Pubmed

11. Imach S, Wafaisade A, Lefering R, et al. The impact of prehospital tranexamic acid on mortality and transfusion requirements: match-pair analysis from the nationwide German TraumaRegister DGU®. Crit Care. 2021;25(1):277. Published 2021 Aug 4. doi:10.1186/s13054-021-03701-7
    Pubmed

12. Roberts I, Ageron FX. The role of tranexamic acid in trauma - a life-saving drug with proven benefit. Nat Rev Dis Primers. 2022;8(1):34. Published 2022 May 26. doi:10.1038/s41572-022-00367-5
    Pubmed

13. Rossetto A, Vulliamy P, Lee KM, Brohi K, Davenport R. Temporal Transitions in Fibrinolysis after Trauma: Adverse Outcome Is Principally Related to Late Hypofibrinolysis. Anesthesiology. 2022;136(1):148-161. doi:10.1097/ALN.0000000000004036

Pubmed