Management of Severe Bleeding or Traumatic Injury

Introduction to Tranexamic Acid

• Tranexamic acid (TXA) is a recommended treatment for significant hemorrhage, with a strength of evidence rated as high, as supported by the World Health Organization (WHO) and other guidelines 1, 2

Prophylactic Use of Tranexamic Acid

• The American College of Critical Care strongly recommends prophylactic use of TXA in all cases of severe bleeding or traumatic injury, administered as soon as possible and ideally within 3 hours of injury at a loading dose of 1g infused over 10 minutes, followed by an intravenous infusion of 1g over 8 hours 3
• Early treatment with TXA, ideally within 1 hour from injury, significantly reduces the risk of death due to bleeding (5.3% vs. 7.7%), with a relative risk reduction of 32% when given within the first hour 2, 3
• Treatment administered between 1-3 hours also shows benefit, with a reduced risk of death due to bleeding (4.8% vs. 6.1%) 2
• The benefit of TXA decreases by approximately 10% for every 15-minute delay, with administration within the first hour having the greatest benefit (RR 0.68), and administration after 3 hours potentially increasing the risk of death (RR 1.44) 2

Dosage and Administration

• The recommended dose of TXA is 1g IV administered over 10 minutes, followed by an infusion of 1g over 8 hours, or a second dose of 1g if bleeding continues after 30 minutes or if it recurs within 24 hours, with a Grade 1A recommendation by the European guideline for management of bleeding and coagulopathy following major trauma 1, 2, 3
• A maintenance dose of 1g IV for 8 hours or a second dose of 1g if bleeding continues is recommended by the American College of Obstetricians and Gynecologists (ACOG), with a strength of evidence rated as high 1, 3
• Patients with renal insufficiency require dose adjustment, with the following recommended doses:

Contraindications and Precautions

• TXA is contraindicated in patients with active intravascular clotting, subarachnoid hemorrhage, known thromboembolic disease, or history of thrombosis or intrinsic risk for thrombosis, as stated by US guidelines and the American Heart Association 1, 4
• TXA is not recommended for the treatment of gastrointestinal bleeding, where evidence shows it does not reduce mortality and may increase the risk of deep vein thrombosis, pulmonary embolism, and seizures 6

Efficacy and Outcomes

• The CRASH-2 study demonstrated that TXA reduces all-cause mortality (14.5% vs 16.0%) and the risk of death due to bleeding (4.9% vs 5.7%) 2
• The WOMAN trial and other studies support the use of TXA in postpartum hemorrhage and traumatic hemorrhage, with a strength of evidence rated as high 1, 2, 3
• Patients receiving TXA within 1 hour of injury with a shock index <0.9 had a 65% lower likelihood of 30-day mortality 3
• In patients with mild and moderate head injury, TXA reduced head injury-related death (RR 0.78, 95% CI 0.64–0.95) 3