Can a patient with impaired renal function on hemodialysis (HD) use Tranexamic Acid?

Tranexamic Acid Use in Hemodialysis Patients

Tranexamic acid can be used in hemodialysis patients, but requires mandatory dose reduction and careful timing of administration after dialysis sessions to prevent severe neurotoxicity and other complications.

Critical Dosing Requirements

The most important consideration is dose adjustment based on renal function. Tranexamic acid is eliminated >95% unchanged through the kidneys via glomerular filtration, and blood levels increase directly with the degree of renal impairment 1. Following a single 10 mg/kg IV injection, only 19% of the drug is excreted in 24 hours when serum creatinine exceeds 5.7 mg/dL, compared to 90% excretion in patients with normal renal function 1.

Specific Dosing Adjustments

• For patients with creatinine clearance <30 mL/min or on hemodialysis: Reduce dosing frequency significantly while maintaining adequate individual doses 2
• Standard approach: Administer the drug after dialysis sessions to facilitate directly observed therapy and avoid premature removal of the drug 2
• Renal clearance equals plasma clearance (110-116 mL/min) in normal function, making dose adjustment essential in dialysis patients 1

Major Toxicity Risks

Neurotoxicity (Most Common)

Neurotoxicity is the predominant clinical manifestation of tranexamic acid toxicity in chronic kidney disease patients. 3 This includes:

• Generalized tonic-clonic seizures occurring within hours of administration in dialysis patients receiving standard doses 4
• Visual impairment and blindness from retinal toxicity, which can develop gradually over 1-2 weeks 5
• Mental status changes, myoclonus, headache, and convulsions 1

The mechanism involves increased incidence of complications (neurotoxicity, ocular toxicity) in patients with renal dysfunction due to drug accumulation 2.

Visual/Retinal Toxicity

• Retinal dysfunction can manifest as microgranular hyperfluorescence indicating malfunction of the pigmented retinal layer 5
• Symptoms may be reversible within days after discontinuation of tranexamic acid 5
• Nonclinical studies show dose-related retinal atrophy commencing with changes to retinal pigmented epithelium and progressing to retinal detachment 1

Thrombotic Complications

• Acute obstructive uropathy from blood clot retention has been reported in kidney transplant recipients taking oral tranexamic acid without dose adjustment 3
• Ureteric clots and acute renal failure from cortical necrosis make chronic renal impairment a relative contraindication 6

Clinical Evidence Supporting Use

Despite the risks, tranexamic acid has been used successfully in hemodialysis patients when properly dosed:

• Life-threatening hematuria in polycystic kidney disease responded to tranexamic acid 1000 mg PO daily (reduced from standard dosing) with cessation of bleeding within 24 hours 6
• Prospective case series of 8 ADPKD patients with gross hematuria showed bleeding stopped within 2-5 days with no thromboembolic events when doses were adjusted for renal function 7
• Recovery from toxicity is typically complete when the drug is discontinued, with symptoms resolving within days 4, 5, 3

Practical Management Algorithm

When Considering Tranexamic Acid in HD Patients:

1. Calculate creatinine clearance using Cockcroft-Gault equation 2
2. Reduce standard dose by 50-75% for patients with CrCl <30 mL/min 2
3. Administer immediately after dialysis sessions to prevent drug removal and facilitate monitoring 2
4. Monitor closely for neurotoxicity: Assess mental status, visual symptoms, and seizure activity within first 24-48 hours 4, 5, 3
5. Consider alternative hemostatic measures first: Desmopressin (0.3 mg/kg IV, max 20 mg) may be safer in special situations with coagulopathy 2

Contraindications in Dialysis Patients:

• Avoid if patient has history of seizures or visual disturbances with prior tranexamic acid use 5
• Do not use standard dosing regimens designed for normal renal function 1, 3
• Caution with concurrent nephrotoxic agents that may further impair drug clearance 2

Key Clinical Pitfalls

The most common error is failure to adjust dosing for renal function. All reported cases of severe toxicity in dialysis patients involved administration of standard doses without adjustment 4, 5, 3. Even a single standard dose can cause toxicity in this population due to prolonged drug accumulation 4.

Timing of administration matters critically. Unlike some medications where timing is flexible, tranexamic acid must be given after dialysis to prevent both premature drug removal and to allow for supervised administration 2.