Can tranexamic acid (TXA) stop an upper gastrointestinal (GI) bleed?

Tranexamic Acid for Upper GI Bleeding

Tranexamic acid (TXA) should not be used routinely for upper gastrointestinal bleeding as it shows no mortality benefit and increases thromboembolic risk, particularly in patients with liver disease. 1, 2

Evidence on TXA in GI Bleeding

Current Guidelines

• The European Association for the Study of the Liver (EASL) strongly recommends against TXA use in variceal bleeding due to increased risk of thromboembolic events, particularly in patients with liver disease 1
• The British Society of Gastroenterology states that use of tranexamic acid in acute lower GI bleeding should be confined to clinical trials 1
• The American Association for the Study of Liver Diseases notes that a recent multicenter trial showed no reduction in death or bleeding with tranexamic acid, with higher risk of venous thromboembolism in patients with cirrhosis 1

Mechanism and Efficacy

• TXA works by inhibiting the breakdown of fibrin clots by plasmin 3
• While TXA has shown benefits in trauma bleeding, its efficacy in GI bleeding is questionable:
  • A large randomized placebo-controlled trial including 12,009 patients with acute upper GI bleeding showed no beneficial effect of TXA on mortality 1
  • Nearly 50% of cases in this trial were suspected variceal bleeding, and no benefit was observed in this subgroup 1

Risks and Complications

• Almost 2-fold increase in venous thromboembolic events was observed in patients receiving TXA compared to placebo 1, 2
• The risk of venous thromboembolic events was concentrated in patients with comorbid liver disease/suspected variceal bleeding 1
• Possible reasons for TXA ineffectiveness in variceal bleeding include:
  1. Limited role of haemostasis in variceal bleeding
  2. Frequent occurrence of hypofibrinolytic state in critically ill patients with cirrhosis 1

Alternative Management Approaches for Upper GI Bleeding

First-line Interventions

• Early endoscopic diagnosis and therapy remain the cornerstone of management
• For suspected variceal bleeding:
  • Prompt initiation of vasoactive therapy (terlipressin, somatostatin, or octreotide) before endoscopy 1, 2
  • Prophylactic antibiotics 2
  • Endoscopic band ligation for varices 2

Blood Product Management

• Use restrictive transfusion threshold (70 g/L, aiming for 70-100 g/L) 2
• Consider higher thresholds for patients with cardiovascular disease 2
• Avoid large volumes of blood products in patients with cirrhosis as they may paradoxically increase portal pressure and worsen bleeding 1, 2

Special Considerations

Anticoagulated Patients

• Interrupt direct oral anticoagulants at presentation 2
• For life-threatening hemorrhage on DOACs, consider specific reversal agents like idarucizumab (for dabigatran) or andexanet alfa (for factor Xa inhibitors) 2
• Restart anticoagulation approximately 7 days after hemorrhage if bleeding source has been controlled 2

Pharmacological Adjuncts

• High-dose IV proton pump inhibitor therapy (80 mg stat followed by 8 mg/hour infusion for 72 hours) following successful endoscopic therapy for ulcer bleeding 2

Conclusion

Despite some older studies suggesting potential benefits, the most recent and highest quality evidence does not support the use of TXA in upper GI bleeding. The increased risk of thromboembolic events, particularly in patients with liver disease, outweighs any potential benefits in controlling bleeding.