Tranexamic Acid (TXA) in Orthopaedics: The Evidence-Based Guide

Visual Element: A diagram of the Coagulation Cascade, specifically highlighting the Fibrinolytic pathway and showing exactly where TXA blocks the Plasminogen-to-Plasmin conversion.

The "Wonder Drug" of Modern Orthopaedics

If you could pick one drug that has transformed orthopaedic surgery outcomes in the last 15 years, it would be Tranexamic Acid (TXA). Cheap, accessible, and remarkably effective, it has virtually eliminated the routine post-operative blood transfusion in primary joint replacement.

But despite its ubiquity, confusion remains. IV or Topical? What about the patient with a stent? Is it safe in hip fractures? This article dissects the evidence to provide clear clinical guidelines.

Mechanism of Action

To understand TXA, you must understand Fibrinolysis.

1. When a clot forms, the body almost immediately starts trying to dissolve it (fibrinolysis) to prevent vessel occlusion.
2. Plasminogen binds to fibrin and is converted to Plasmin, which acts as "molecular scissors" to cut the fibrin clot.
3. TXA is a synthetic lysine analogue. It acts as a "decoy," blocking the lysine binding sites on Plasminogen.
4. Result: Plasminogen cannot bind to fibrin. The clot remains stable. Bleeding stops.

Clinical Pearl: TXA does not create new clots (it is not pro-thrombotic). It simply prevents the breakdown of existing clots. This is a critical distinction for safety.

Evidence by Subspecialty

1. Arthroplasty (Hip & Knee)

The evidence here is overwhelming.

• Impact: Reduces blood loss by ~500ml and transfusion rates by >60%.
• Standard of Care: It is now considered negligent not to use TXA in standard arthroplasty without a contraindication.
• Topical vs. IV: The ATAC Trial and multiple meta-analyses show that Topical (Intra-articular) TXA is non-inferior to IV TXA.
  • Protocol: 1-3g diluted in saline, bathed in the joint for 5-10 mins before closure.
• Combined: Some evidence suggests Combined IV + Topical is superior for high-blood-loss cases (revisions, bilaterals).

2. Trauma (The CRASH-2 Trial)

The CRASH-2 trial (20,000+ patients) is one of the most important papers in medical history.

• Finding: TXA reduces all-cause mortality in bleeding trauma patients.
• The Golden Window: It must be given within 3 hours of injury.
• The Trap: Giving TXA after 3 hours was associated with increased mortality (likely due to DIC phase).
• Dose: 1g IV bolus (over 10 min) + 1g infusion over 8 hours.

3. Spine Surgery

TXA is highly effective in reducing blood loss in long-segment fusions and deformity correction. High-dose protocols (10-30mg/kg bolus + infusion) are often used.

The High-Risk Patient: VTE and Cardiac History

This is the most common consult question: "Can I give TXA to Mrs. Jones? She had a PE 5 years ago."

The Fear

Surgeons worry that stabilizing clots will cause a DVT or PE.

The Evidence

• POISE-3 Trial: A massive RCT demonstrating that TXA is safe in patients with cardiovascular risk.
• VTE History: Most recent guidelines suggest that a remote history (>12 months) of VTE is not a contraindication, especially for Topical use. The risk of transfusion (which itself is immunomodulatory and pro-thrombotic) is likely higher than the risk of the TXA.
• Stents: Patients with coronary stents are generally safe to receive TXA, as their anti-platelet therapy manages the arterial risk, while TXA manages fibrinolysis.

Evidence Corner: Systemic absorption of Topical TXA is negligible (approx 70% lower plasma concentration than IV). For high-risk patients, Topical is the logical safe haven.

Contraindications

Absolute

• Active intravascular clotting: A patient currently being treated for DVT/PE.
• Hypersensitivity: Rare anaphylaxis.
• Subarachnoid Haemorrhage: Specific neurosurgical contraindication (can cause cerebral ischemia).

Relative

• Renal Failure: TXA is renally excreted. Doses must be reduced in CKD to avoid toxicity.
• History of Seizures: High-dose IV TXA blocks GABA receptors in the brain and can lower the seizure threshold. Avoid high doses in epileptics.
• Colour Blindness: Chronic high-dose usage is linked to retinal toxicity. A single peri-operative dose is theoretically safe, but often listed as a caution.

Dosing Protocols

Standard Arthroplasty

• IV: 1g (or 15mg/kg) at induction. Repeat 1g at closure if case >3 hours.
• Topical: 2g in 50ml Saline. Lavage joint, aspirate excess, close drain (or no drain).

Hip Fracture

• IV: 1g at induction. Safe and effective, even in this frail population. Reduces transfusion risk significantly.

Conclusion

Tranexamic Acid is a low-risk, high-reward intervention.

• Default: Yes.
• Route: IV is easiest. Topical is safest for high-risk.
• Timing: Early is better. In trauma, <3 hours is mandatory.

By mastering the use of TXA, you protect your patient from the risks of anaemia and allogeneic blood transfusion, speeding up their recovery and discharge.

References

1. CRASH-2 Trial Collaborators. "Effects of tranexamic acid on death... in bleeding trauma patients." Lancet. 2010.
2. POISE-3 Investigators. "Tranexamic Acid in Patients Undergoing Noncardiac Surgery." NEJM. 2022.
3. Fillingham YA, et al. "Tranexamic acid in total joint arthroplasty... Clinical Practice Guidelines." J Arthroplasty. 2018.