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

Tranexamic Acid for Upper GI Bleeding

Tranexamic acid (TXA) should not be routinely used for the management of upper GI bleeding as it does not significantly reduce mortality and may increase thromboembolic risk, particularly in patients with liver disease. 1

Evidence on TXA in Upper GI Bleeding

Efficacy and Safety Concerns

The most recent and highest quality evidence from clinical guidelines indicates that TXA has limited efficacy in upper GI bleeding:

• A large randomized placebo-controlled trial including over 12,000 patients with acute upper GI bleeding showed no beneficial effect of TXA on mortality due to bleeding 1
• While some meta-analyses suggest TXA may reduce rebleeding rates and need for surgery 2, 3, these findings have not translated to mortality benefits
• Concerning safety profile: TXA was associated with an almost 2-fold increase in venous thromboembolic events, with risk particularly concentrated in patients with liver disease/suspected variceal bleeding 1

Specific Clinical Scenarios

Non-variceal Upper GI Bleeding

• A meta-analysis showed that TXA therapy appears to reduce the need for surgical intervention and tends to reduce mortality in ulcer bleeding patients, but does not reduce ulcer rebleeding 1
• However, this meta-analysis was likely skewed by inclusion of an extremely large trial with unusually high mortality in the control group 1
• Current guidelines state that "further studies of tranexamic acid are necessary before it can be recommended as routine therapy" 1

Variceal Upper GI Bleeding

• In patients with cirrhosis and active variceal bleeding, TXA should not be used (strong recommendation) 1
• The ineffectiveness in variceal bleeding may be due to:
  1. Limited role of hemostasis in variceal bleeding
  2. Frequent occurrence of hypofibrinolytic state in critically ill patients with cirrhosis 1

Current Standard of Care for Upper GI Bleeding

Instead of TXA, the following interventions are recommended:

1. For non-variceal bleeding:

   • Endoscopic therapy as primary intervention
   • High-dose proton pump inhibitor therapy (80 mg stat followed by 8 mg hourly for 72 hours) following successful endoscopic therapy 1
   • Repeat endoscopy for evidence of rebleeding or suboptimal initial therapy 1

2. For variceal bleeding:

   • Prompt initiation (before endoscopy) of vasoactive therapy (terlipressin, somatostatin or octreotide)
   • Antibiotics
   • Endoscopic band ligation 1
   • Restrictive red blood cell transfusion strategy (target hemoglobin 70-100 g/L) 1, 4

Pitfalls and Caveats

• Do not use TXA in patients with cirrhosis and variceal bleeding due to increased risk of venous thromboembolic events 1
• Avoid large volume transfusions of blood products in patients with cirrhosis as this can paradoxically increase portal pressure and worsen bleeding 1
• While some smaller studies and meta-analyses suggest potential benefits of TXA 2, 5, 3, these findings are outweighed by the large, high-quality trial showing no mortality benefit and increased thrombotic risk 1
• A recent randomized controlled trial of locally administered TXA showed no additional benefit over standard care in patients with upper GI hemorrhage 6

In summary, while TXA has proven benefits in trauma and surgical bleeding, current evidence does not support its routine use in upper GI bleeding, and it should be avoided particularly in patients with liver disease or variceal bleeding.