Can tranexamic acid (TXA) use increase the risk of clotting in patients undergoing hemodialysis?

Tranexamic Acid in Hemodialysis: Significant Clotting Risk with Critical Dosing Considerations

Tranexamic acid can cause clotting complications in hemodialysis patients and requires mandatory dose reduction, but when used appropriately at reduced doses, it may be beneficial for specific bleeding indications in this population.

Critical Pharmacokinetic Concerns in Hemodialysis

The primary concern with TXA in hemodialysis patients stems from impaired renal clearance, as approximately 90% of TXA is excreted unchanged in urine within 24 hours in patients with normal renal function 1, 2. This creates several compounding risks:

• Prolonged drug accumulation: In dialysis patients, TXA demonstrates markedly prolonged elimination with plasma levels remaining elevated for extended periods. A case report documented TXA levels of 71 μg/dL immediately post-dose, decreasing only to 25 μg/dL at 6 hours, with no further decrease until hemodialysis was performed 3.

• Persistent fibrinolytic shutdown: Even after hemodialysis reduced TXA levels from 25 to 6.9 μg/dL, complete fibrinolytic shutdown persisted for 48 hours postoperatively, demonstrating that the pharmacodynamic effects outlast measurable plasma concentrations 3.

• Increased toxicity risk: Renal clearance is the major mechanism of TXA excretion, and impaired clearance correlates with increased incidence of neurotoxicity and ocular toxicity 1, 4.

Thrombotic Risk Profile

The FDA explicitly warns that TXA is an antifibrinolytic agent that may increase the risk of thromboembolic events, with venous and arterial thrombosis reported in treated patients 5. This risk is particularly relevant in hemodialysis patients who already face elevated baseline thrombotic risk:

• TXA is contraindicated in patients with active intravascular clotting 5.

• The drug should be avoided with concomitant pro-thrombotic medications including Factor IX concentrates, anti-inhibitor coagulant concentrates, and hormonal contraceptives 5.

• While the CRASH-2 trauma trial showed lower thrombosis rates with TXA use, this was in a different clinical context (acute trauma with hemorrhagic shock and hemodilution), not chronic hemodialysis patients 1.

Mandatory Dose Adjustments for Renal Impairment

The FDA mandates specific dose reductions based on serum creatinine levels 5:

• Serum creatinine 1.36-2.83 mg/dL: 10 mg/kg twice daily
• Serum creatinine 2.83-5.66 mg/dL: 10 mg/kg once daily
• Serum creatinine >5.66 mg/dL: 10 mg/kg every 48 hours OR 5 mg/kg every 24 hours

For patients on hemodialysis (functionally equivalent to serum creatinine >5.66 mg/dL), the most conservative dosing should be employed 5.

Evidence for Efficacy in Dialysis Patients

Despite the risks, there is limited evidence supporting TXA use for specific indications:

• Upper GI bleeding: A pilot study of 20 dialysis patients with 36 episodes of major upper GI bleeding showed that TXA (20 mg IV followed by 10 mg/kg/48h orally for 4 weeks) significantly reduced early rebleeding (0 vs 6 episodes, P<0.05), total rebleeding in the first month (1 vs 8 episodes, P<0.05), and transfusion requirements (1.4±1.3 vs 2.6±1.5 units, P<0.05) 6.

• Importantly, this study used severely reduced dosing compared to standard protocols, and the decision to use TXA was reserved for the most severe bleeding cases 6.

Clinical Algorithm for TXA Use in Hemodialysis

When considering TXA in hemodialysis patients:

1. Assess absolute contraindications 5:

   • Active intravascular clotting (absolute contraindication)
   • Recent thrombotic events or stroke (contraindicated in active thromboembolic disease) 4
   • Subarachnoid hemorrhage (contraindicated) 5

2. Evaluate bleeding severity: Reserve TXA only for life-threatening hemorrhage where benefits clearly outweigh thrombotic risks 6.

3. Use reduced dosing: Consider doses <1 g total to minimize seizure and thromboembolic complications 3. The evidence supports 10 mg/kg every 48 hours as the maximum safe dose 5.

4. Monitor closely:

   • Watch for signs of thrombosis (dialysis access clotting, deep vein thrombosis, pulmonary embolism)
   • Monitor for seizures (increased risk with renal dysfunction) 5
   • Consider EEG monitoring if any myoclonic movements occur 5

5. Discontinue as soon as bleeding is controlled: The prolonged half-life in dialysis patients means effects persist long after administration 4, 3.

Critical Pitfalls to Avoid

• Never use standard dosing: The typical 1 g loading dose followed by 1 g over 8 hours used in trauma 1 is inappropriate and dangerous in dialysis patients due to accumulation 3.

• Do not assume dialysis will rapidly clear TXA: While hemodialysis does remove TXA, the pharmacodynamic effects on fibrinolysis persist well beyond drug clearance 3.

• Avoid in routine or minor bleeding: The European Association for the Study of the Liver recommends against routine TXA use for procedural bleeding even in cirrhotic patients due to thrombotic concerns 1, 2, and this caution applies even more strongly to dialysis patients with impaired clearance.

• Watch for dialysis access thrombosis: This is a particularly relevant thrombotic complication in this population that could result in loss of vascular access.