What is the preferred route of administration, intravenous (IV) tranexamic acid (TXA) or topical tranexamic acid (TXA), for a patient at risk of significant bleeding?

Intravenous Tranexamic Acid vs Topical Tranexamic Acid for Significant Bleeding

For patients at risk of significant bleeding, intravenous (IV) tranexamic acid is the only evidence-based and guideline-recommended route of administration. 1, 2

Route of Administration: IV is the Standard of Care

Intravenous administration is the only FDA-approved and evidence-based route for acute hemorrhage. 2, 3

• Current clinical guidelines do not include specific recommendations for topical or intramuscular dosing of TXA in trauma or major bleeding scenarios. 4, 5
• The landmark CRASH-2 trial, which demonstrated mortality reduction in 20,211 trauma patients, exclusively used IV administration. 1
• All major international guidelines (European, American College of Surgeons, American Society of Anesthesiologists) recommend IV administration only. 1, 2

Standard IV Dosing Protocol

The recommended dose is 1 g IV loading dose over 10 minutes, followed by 1 g IV infused over 8 hours. 1, 2

• This regimen reduced all-cause mortality from 16.0% to 14.5% (relative risk 0.91,95% CI 0.85-0.97) and death due to bleeding from 5.7% to 4.9% (relative risk 0.85,95% CI 0.76-0.96) in the CRASH-2 trial. 1
• Infuse no more than 1 mL/minute to avoid hypotension. 3

Critical Timing Considerations

TXA must be administered within 3 hours of injury or bleeding onset—administration after 3 hours may paradoxically increase mortality. 1, 2

• Early treatment (≤1 hour) significantly reduced death due to bleeding (5.3% vs 7.7%; RR 0.68,95% CI 0.57-0.82). 1
• Treatment between 1-3 hours also reduced bleeding deaths (4.8% vs 6.1%; RR 0.79,95% CI 0.64-0.97). 1
• Treatment after 3 hours increased risk of death due to bleeding (4.4% vs 3.1%; RR 1.44,95% CI 1.12-1.84). 1
• Effectiveness decreases by 10% for every 15-minute delay in administration. 4, 2, 5

Pre-Hospital Administration

Protocols should consider administering the first dose of TXA at the site of injury to ensure early treatment. 1

• Pre-hospital administration is recommended to maximize the likelihood of treatment within the critical 3-hour window. 1, 4

Why Topical TXA is Not Recommended for Major Bleeding

The evidence base for TXA in life-threatening hemorrhage is exclusively based on IV administration:

• No guideline recommends topical TXA for trauma or major bleeding scenarios. 1, 4, 2, 5
• The FDA label for TXA injection specifies IV use only for hemorrhage control. 3
• Topical TXA may have a role in localized surgical bleeding (e.g., orthopedic surgery), but this is a fundamentally different clinical context than systemic hemorrhage. 6, 7

Safety Profile of IV TXA

IV TXA does not increase thrombotic risk in major bleeding patients and actually showed lower rates of myocardial infarction in CRASH-2. 1

• No adverse events were described with standard dosing in CRASH-2. 1
• Higher doses (>100 mg/kg) are associated with increased seizure risk, particularly in cardiac surgery. 1, 4, 2
• The standard trauma dose (2 g total) is well below the seizure-risk threshold. 4, 2

Absolute Contraindications

Do not administer TXA in subarachnoid hemorrhage due to risk of cerebral edema and infarction. 2, 3

• TXA is also contraindicated in patients with active intravascular clotting or hypersensitivity to the drug. 3

Common Pitfalls to Avoid

• Never delay administration beyond 3 hours—this is associated with increased mortality. 1, 2, 5
• Never administer intrathecally—serious adverse reactions including seizures and cardiac arrhythmias have occurred with incorrect route administration. 3
• Never use in subarachnoid hemorrhage—this is an absolute contraindication. 2, 3
• Clearly label syringes with "INTRAVENOUS ONLY" to prevent route confusion. 3

Dose Adjustments

Reduce dosing in patients with renal impairment, as TXA is predominantly excreted unchanged by the kidneys. 2, 3

• For serum creatinine 1.36-2.83 mg/dL: 10 mg/kg twice daily. 3
• For serum creatinine 2.83-5.66 mg/dL: 10 mg/kg daily. 3
• For serum creatinine >5.66 mg/dL: 10 mg/kg every 48 hours or 5 mg/kg every 24 hours. 3