Tranexamic Acid Primer

Tranexamic Acid (TXA)

What is it?

• TXA is an antifibrinolytic drug → TXA is synthetic analog of lysine that competitively binds to the lysine sites on plasminogen that prevents conversion of plasminogen to plasmin. This action prevents fibrinolysis (the breakdown of fibrin) and promotes clot stability.
• Easy way to look at it → TXA is (in essence) the polar opposite of tPA.

Why should we worry about this in trauma?

• Hyperfibrinolysis is present in 7-20% of all adult trauma patients and is associated with increased mortality; some studies cite it is present in up to 57% of all trauma patients. [1,2]
• If present, hyperfibrinolysis occurs early (<1 hour) and is associated with increased massive transfusion requirements, coagulopathy, and hemorrhage-related death. [3]
• Mortality rate has been reported to be approximately 88% in trauma patients with hyperfibrinolysis on admission detected by TEG/TEM. [3]

Does it work/What are the risks?

CRASH-2 Trial: [4]

• Prospective, double-blind, multinational, randomized, placebo-controlled trial.
• 274 hospitals. 40 countries. 
• 20,211 adult trauma patients (10,060 treatment arm - 10,067 placebo arm) with or at risk of significant bleeding ("all-comers")
• SIGNIFICANT reduction in all-cause mortality if given within 3 hours of injury (RR= 0.91; 95% CI 0.85 to 0.97; P=.004)
• NO INCREASE in fatal vascular occlusive events or in deaths caused by multiple organ failure, head injury, etc.

MATTERS Trial: [5]

• Retrospective, observational, single-center, "before & after" cohort study from Jan 2009 to Dec 2010.
• 896 military combat trauma patients who received at least 1 unit of PRBCs after admission.
• TXA was incorporated into the center's "major hemorrhage protocol" in 2010 - results were compared between the 2 groups. 
• Patients who received > 10 units RBCs within 24 hours were also subdivided into a "Massive Transfusion" cohort.
• SIGNIFICANT reduction in-hospital mortality in TXA group → absolute reduction in-hospital mortality in TXA group was 6.5% and in the TXA "massive transfusion" group was 13.7% → Relative reduction of 49%.
• The authors quote:

"In a separate analysis, none of the clinical parameters had an association with DVT or PTE in either the overall or MT cohort. As such, no parameters, including administration of TXA, were associated with DVT or PTE"

Conclusion

• Early administration of TXA in the severe trauma patient in the prehospital setting is a NO-BRAINER.

1) Kutcher et al. J Trauma 2012; 73:87-93

2) Raza et al. J Thromb Haemost 2013; 11(2):307-14

3) Schochl et al. J Trauma 2009; 67(1):125-31

4) CRASH-2 Collaborators. Lancet 2010; 376:23-32

5) Morrison et al. Arch Surg 2012; 147(2):113–9