What is the approach to using tranexamic acid (TXA) in patients with cardiovascular disease (CVD) who experience bleeding?

Tranexamic Acid in Patients with Cardiovascular Disease Who Experience Bleeding

Tranexamic acid (TXA) can be safely used in patients with cardiovascular disease experiencing bleeding, as recent meta-analyses show no increased risk of thromboembolic complications in these patients, supporting the general safety of the drug. 1

Safety Profile in Cardiovascular Disease Patients

TXA is a synthetic derivative of lysine that inhibits plasminogen activation, thus inhibiting fibrinolysis. Its effectiveness has been well-established across various clinical settings:

• A meta-analysis of 216 trials (125,550 participants) found no evidence of increased thromboembolic complications with TXA use 1
• A more recent meta-analysis focusing specifically on non-cardiac surgery (191 RCTs, 40,621 participants) also found no evidence of increased cardiovascular thromboembolic complications, seizures, or mortality at 30 days 1
• The POISE-3 trial (9,535 patients undergoing non-cardiac surgery) demonstrated that TXA significantly reduced bleeding outcomes compared to placebo (9.1% vs 11.7%) with only a small, non-significant difference in cardiovascular outcomes (14.2% vs 13.9%) 2

Dosing Recommendations

For patients with cardiovascular disease experiencing bleeding, the following dosing approaches are recommended:

Trauma-related bleeding:

• Loading dose of 1g infused over 10 minutes, followed by intravenous infusion of 1g over 8 hours 1
• Critical timing: TXA should be administered within 3 hours of injury, as treatment after this window may increase mortality risk 1, 3
• Consider protocols that enable administration of the first dose en route to the hospital 1

Surgical bleeding:

• Standard dosing as per surgical protocols, with evidence showing a 29% reduction in blood loss with topical application 4
• For cardiac and major non-cardiac surgery, follow institutional protocols for dosing 1

Special Considerations

Gastrointestinal Bleeding:

• The European Association for the Study of the Liver and European Society of Intensive Care Medicine recommend against routine TXA use in gastrointestinal bleeding based on high-certainty evidence 3
• If considered, low-dose IV or enteral TXA may reduce rebleeding and need for surgical intervention, though evidence is limited 3

Patients with Cirrhosis:

• Use with caution in patients with cirrhosis
• For patients with portal hypertension-related bleeding, portal hypertension-lowering measures should be the primary approach 1, 3
• Correction of coagulopathy should be considered only on a case-by-case basis if bleeding persists 3

Renal Considerations:

• TXA is primarily eliminated through renal clearance (90% excreted in urine within 24 hours) 1
• Reduced doses are indicated in patients with chronic or acute renal failure 1
• Use with caution in renal dysfunction due to increased risk of neurotoxicity and ocular toxicity 1

Contraindications and Cautions

• Contraindicated in disseminated intravascular coagulation (DIC) 1

• Use with caution in patients with:

  • Massive hematuria (risk of ureteric obstruction) 1
  • Patients on oral contraceptive pills (increased thrombosis risk) 1
  • Chronic liver failure (potential worsening of bleeding symptoms) 5

• Dose-dependent seizure risk: Avoid very high doses (>2g/day) due to increased seizure risk 6

Monitoring

When administering TXA to patients with cardiovascular disease:

• Monitor for clinical signs of thrombosis
• For patients requiring massive transfusion, monitor calcium levels 3
• In patients on anticoagulants, consider withholding the anticoagulant and using specific reversal agents for severe bleeding with DOACs 3

Algorithm for Decision-Making

1. Assess bleeding severity and source
2. Determine time from injury/onset of bleeding
   • If trauma-related and <3 hours: Administer TXA promptly
   • If >3 hours: Consider alternative hemostatic strategies
3. Evaluate cardiovascular status and risk factors
4. Check renal function
   • Normal: Standard dosing
   • Impaired: Reduce dose accordingly
5. Consider contraindications
   • DIC: Avoid TXA
   • Massive hematuria: Use with extreme caution
6. Select appropriate dosing based on bleeding context
7. Monitor for thrombotic complications and seizures

By following this evidence-based approach, TXA can be safely and effectively used in patients with cardiovascular disease who experience bleeding, with appropriate consideration of timing, dosing, and patient-specific factors.