Tranexamic Acid in Critical Care

Key Takeaways

🎯 Most Important Points

3 hrs

Window for TXA efficacy — give ASAP

NNT 67

Patients to prevent 1 trauma death (CRASH-2)

1 + 1 g

Standard dose: 1g bolus + 1g/8hrs

HALT-IT

GI Bleed: NO benefit — avoid TXA

⚠️ Critical Warning: Do NOT give TXA >3 hours after injury — may increase mortality. Efficacy diminishes 10% for every 15-minute delay.

Evidence Base

Landmark Trials — Comprehensive Appraisal

Trauma hemorrhage | n=20,211

✅ 14.5% vs 16.0% mortality (RR 0.91) | NNT = 67
<1hr: ↓32% death | 1-3hr: ↓21% death | >3hr: no benefit

Postpartum hemorrhage | n=20,060 women

✅ 1.5% vs 1.9% death from PPH (p=0.03) | NNT ≥500
Greatest benefit within 3 hours of childbirth

Traumatic brain injury | n=12,737

⚠️ Non-statistically significant reduction in head injury death
Possible benefit in severe TBI (GCS ≤8) | No safety concerns

Pre-hospital TXA | n=1,310 | Australia, NZ, Germany

⚠️ 4 extra survivors/100 at 6 months — but more severely disabled
Confirmed mortality benefit at 24hrs/28days | No ↑ VTE

Acute GI bleeding | n=12,009

❌ NO mortality benefit | ↑ Seizures | ↑ VTE
TXA should NOT be used for GI bleeding outside RCT

Non-cardiac surgery | n=9,535

✅ ↓ Major bleeding by ~25% (9% vs 12%) | No ↑ CV events
Consistent across surgery types

Pharmacology

Mechanism of Action

Antifibrinolytic Effect

TXA is a synthetic lysine derivative that works by:

Competitive inhibition — binds to lysine binding sites on plasminogen
Prevents plasminogen activation — blocks conversion to plasmin
Stabilizes fibrin clot — prevents clot breakdown

Dosing

Standard Protocol (CRASH-2)

Loading dose: 1 gram IV over 10 minutes

Maintenance: 1 gram IV over 8 hours

Total dose: 2 grams over 8 hours

Alternative: 1g bolus IV over 10 min, repeat once over 8 hrs (max 2g)

Pediatric Dosing

Weight	Loading Dose	Maintenance
<50 kg	20 mg/kg IV over 10 min	10 mg/kg/hr over 8 hrs
≥50 kg	Adult dosing	Adult dosing

Guidelines

2025–2026 Clinical Recommendations

NICE 2025-2026

Surgery

Offer TXA if breach of skin/mucosa in operating theatre
Consider if expected blood loss >500 mL outside OR
Draft guidance extends to pediatric surgery

EAST 2025

Trauma

Conditional recommendation for pre-hospital TXA
Conditional recommendation for in-hospital TXA
Mortality benefit at 24 hrs and 1 month

NAEMSP/ACEP/ACS-COT 2025

Prehospital

Recommend prehospital TXA in hemorrhagic shock
Within 3 hours of injury
Low risk of thromboembolic events

ACG 2023-2024

GI Bleeding

Upper GI: Mixed evidence (possible benefit)
Lower GI: Strong recommendation AGAINST

Safety

Contraindications & Cautions

❌ Absolute Contraindications

Hypersensitivity to TXA
Active venous or arterial thrombosis
Subarachnoid hemorrhage

⚠️ Relative Contraindications

History of convulsions (TXA lowers seizure threshold)
Severe renal impairment (drug accumulation)
DIC
History of thromboembolism

Adverse Effects

System	Adverse Effect	Frequency
GI	Nausea, vomiting, diarrhea	Common
CNS	Seizures (especially high dose/rapid infusion)	Rare
CV	Hypotension (rapid IV push)	Rare
Thromboembolic	DVT, PE (low risk per CRASH-2)	Rare

Summary

Clinical Applications

Setting	Recommendation	Key Evidence
Trauma hemorrhage	Strong recommend	CRASH-2: NNT 67, ↓mortality 32% (<1hr)
TBI	Conditional	CRASH-3: Possible benefit in severe TBI
Postpartum hemorrhage	Recommend	WOMAN: ↓death from PPH
Non-cardiac surgery	Recommend	POISE-3: ↓bleeding 25%
Pre-hospital trauma	Conditional	PATCH: 4 extra survivors but more disabled
Upper GI bleeding	Mixed evidence	HALT-IT: No mortality benefit shown
Lower GI bleeding	Against	HALT-IT: ↑seizures/VTE, no benefit