Tranexamic Acid (TXA) in Traumatic Internal Bleeding

1. Dosing and Administration

The World Health Organization (WHO) recommends a loading dose of 1 g TXA administered intravenously over 10 minutes, followed by a maintenance infusion of 1 g over 8 hours in any adult with suspected internal bleeding from trauma【1】【2】.
This regimen, derived from the CRASH‑2 randomized trial (20,211 patients), is considered high‑quality evidence and remains the gold‑standard protocol【1】【2】【6】.

Within 1 hour of injury: TXA provides the greatest survival advantage, reducing death from bleeding by 32 % (RR 0.68)【1】【3】 – evidence from a large RCT (high certainty).
Between 1–3 hours: A moderate benefit persists, with a 21 % reduction in bleeding‑related mortality (RR 0.79)【4】【5】 – still supported by the CRASH‑2 data (moderate‑high certainty).
After 3 hours: No mortality benefit and a possible increase in death from hemorrhage (RR 1.44); therefore, the American College of Surgeons defines administration beyond 3 hours as an absolute contraindication【4】【6】【5】【7】.

The standard 2 g total dose lowered all‑cause mortality from 16.0 % to 14.5 % (RR 0.91) and death from bleeding from 5.7 % to 4.9 % (RR 0.85)【3】【8】 – derived from high‑quality trial data.

A single 1 g bolus may achieve outcomes comparable to the bolus‑plus‑infusion regimen, offering logistical simplicity【2】【6】 (moderate evidence).
Higher total doses (up to 3 g) have been explored in hypotensive patients in the STAAMP trial; this approach remains investigational【2】【6】.

TXA should be given to trauma patients with active bleeding or a high risk of significant hemorrhage, defined by any of the following:
- Systolic blood pressure < 90 mmHg【2】
- Heart rate > 110 bpm【2】
- Clinical judgment of substantial bleeding risk【7】
Mortality reduction is consistent across all baseline probabilities of death, so TXA should not be limited to only the most severely injured【2】【6】【9】.

Absolute contraindications (per the American Society of Critical Care Medicine):
- Subarachnoid hemorrhage (risk of cerebral edema/infarction)【10】
- Severe hypersensitivity to TXA【4】
Relative caution: History of seizures—high‑dose regimens (>2 g) increase seizure risk【1】【8】.

For patients with severe renal impairment (eGFR < 30 mL/min/1.73 m²), the American Society of Nephrology advises reducing the maintenance infusion dose by 50 % or using a single 1 g bolus only【8】 (expert consensus).

TXA does not increase thrombotic risk in trauma patients【1】【3】【8】 – high‑quality evidence.
The CRASH‑2 trial reported lower rates of myocardial infarction with TXA【4】.
No increase in venous thromboembolism was observed in large trauma cohorts (American Society of Anesthesiologists)【2】【11】, and the PATCH trial confirmed no difference in thrombotic events (23.6 % vs 19.7 %)【2】【11】.

Do not wait for laboratory confirmation (e.g., viscoelastic testing) before administering TXA; base the decision on clinical criteria【10】.
Do not delay TXA awaiting activation of a massive transfusion protocol; benefits apply to all bleeding trauma patients【7】.
Never administer TXA after 3 hours post‑injury, as the mortality benefit reverses and harm may occur【4】【5】.
Avoid excessive dosing (>2 g), which raises seizure risk without added benefit【1】【8】.

The American College of Emergency Physicians recommends administering the first 1 g bolus en route to the hospital when feasible【1】【3】【7】.