Injuries are a major cause of death worldwide. Millions of people die every year from traffic injuries. In fact, they are the 9th leading cause of death around the world. Additionally, another 1.5 million people die every year from interpersonal violence. Hemorrhage accounts for about 1/3 of all trauma deaths and as such, it should be our goal to find treatments to decrease death from hemorrhage.
Our bodies have a finely tuned system that allows blood to flow freely and not clot too easily while also allowing the body to form clots when needed. This balance is upset in trauma by loss of blood and factors, acidosis, hypothermia and the inflammatory cascade. Hyperfibrinolysis often occurs making hemostasis extremely challenging.
Tranexamic Acid (TXA) is a synthetic derivative of lysine that inhibits fibrinolysis and thus stabilizing clots that are formed. TXA has been widely used in elective surgical cases and has shown decreased need for blood transfusion and reduction in mortality. It makes sense, then to apply TXA to the trauma patient to see if we can get similar effects.
Does the early administration of TXA decreased mortality in patients with major trauma?
Adult trauma patients within 8-hours of injury with or at risk of significant bleeding, from 274 hospitals in 40 countries. N=20, 211). Significant haemorrhage was defined as systolic blood pressure < 90mm Hg or heart rate > 110 beats per minute or both.
Loading dose of 1 g of tranexamic acid infused over 10 minutes, followed by an intravenous infusion of 1 g over 8 h (n=10,060).
0.9% Normal Saline (n=10,067).
Primary: Death in hospital within 4 weeks of injury.
Secondary: Receipt of a blood-products transfusion, number of units of blood products transfused, surgical intervention, occurrence of thromboembolic episodes (stroke, myocardial infarction, pulmonary embolism, clinical evidence of DVT).
Multicenter, randomized, double-blind controlled trial
Patients for whom the responsible doctor considered that there was a clear indication for tranexamic acid were not randomly assigned. Similarly, patients for whom there was considered to be a clear contraindication to TXA treatment were not randomly assigned.
- 20,211 patients randomized within 8 hours of injury
- All cause mortality: 16% (placebo group) vs 14.5% (TXA group) (RR 0.91, 95% CI 0.85-0.97) p = 0.0035
- Absolute risk reduction: 1.5%
- NNT = 68 (95% CI 0-206) for death
There was no significant difference between any of the secondary outcomes.
- Receipt of a blood-products transfusion
- Number of units of blood products transfused
- Surgical intervention
- Occurrence of thromboembolic episodes (stroke, myocardial infarction, pulmonary embolism, clinical evidence of DVT)
Tranexamic acid significantly benefited the subset with systolic blood pressure <75mmHg (RR 0.87; 95% CI 0.76- 0.99).
- Large, pragmatic, real-world, multicenter trial
- Follow-up was excellent. Only 80 patients were lost to follow up
- The primary outcome was patient centered
- Patients could be excluded if the treating doctor thought “there was a clear indication for tranexamic acid,” or “a clear contraindication to tranexamic acid.”
- Advanced trauma systems (as seen in countries with developed medical systems) were not represented in this study.
“TXA safely reduced the risk of death in bleeding trauma patients in this study. On the basis of these results, tranexamic acid should be considered for use in bleeding trauma patients.”
We agree with the authors’ conclusions.
Potential Impact To Current Practice
CRASH 2 was a game-changer in trauma care. The majority of trauma centers in the world are employing this drug or considering adding it to their treatment algorithm. TXA is an inexpensive, readily available drug making the results of this study far-reaching.
The use of tranexamic acid in the trauma patient with significant bleeding reduces mortality by 1.5% without increasing thromboembolic events. TXA is a safe and effective treatment in patients with hemorrhagic shock from trauma in reducing mortality. It is an inexpensive therapy, which should be included in the care of these critically injured patients.
St. Emlyn’s JC: Tranexamic Acid for Everyone?
St. Emlyn’s JC: Tranexamic Acid – Does the Evidence Stack Up?
EMCrit Podcast 67 – Tranexamic Acid (TXA), CRASH-2, & Pragmatism with Tim Coats
SGEM#80: CRASH-2 (Classic Paper)