When is Tranexamic acid (TXA) contraindicated?

When is Tranexamic Acid (TXA) Contraindicated?

Tranexamic acid is absolutely contraindicated in patients with subarachnoid hemorrhage, active intravascular clotting (including disseminated intravascular coagulation), and documented hypersensitivity to the drug. 1

Absolute Contraindications

Subarachnoid Hemorrhage

• TXA must never be used in subarachnoid hemorrhage, as anecdotal experience indicates it may cause cerebral edema and cerebral infarction in these patients 1
• While TXA reduces rebleeding in subarachnoid hemorrhage, it increases ischemic complications, making the risk-benefit ratio unfavorable 2

Active Intravascular Clotting

• TXA is contraindicated in patients with active intravascular clotting or disseminated intravascular coagulation (DIC) 1, 3
• The routine use of TXA in cancer-related DIC cannot be recommended and may be deleterious, except potentially in hyperfibrinolytic DIC with therapy-resistant bleeding 3

Hypersensitivity

• Documented hypersensitivity to tranexamic acid or any ingredient is an absolute contraindication, including history of anaphylactic reactions 1

Relative Contraindications and High-Risk Situations

Thrombotic History

• TXA should be avoided in patients with known thromboembolic disease or history of thrombosis 4, 3
• This is particularly important for long-term maintenance therapy in conditions like hereditary angioedema, where tranexamic acid is contraindicated in patients with a history of thrombosis 3

Concurrent Use with Prothombotic Agents

• Avoid concomitant use with activated prothrombin complex concentrates (aPCC) - tranexamic acid is specifically contraindicated in conjunction with aPCC administration according to prescribing information 3
• Exercise caution with Factor IX Complex concentrates, Anti-inhibitor Coagulant concentrates, and hormonal contraceptives due to increased thrombotic risk 1

Massive Hematuria

• Use with extreme caution in patients with massive hematuria due to risk of ureteric obstruction from clot formation 3

Timing-Related Contraindication

• Administration beyond 3 hours after onset of acute bleeding (trauma, postpartum hemorrhage) may be potentially harmful and increase risk of death due to bleeding 5, 6
• This represents a critical window where TXA transitions from beneficial to potentially dangerous 5

Special Populations Requiring Dose Adjustment (Not Absolute Contraindications)

Renal Impairment

• Severe renal impairment requires dose adjustment, as TXA is renally excreted and accumulates in renal failure 3, 7
• Most randomized trials exclude patients with creatinine >250 μmol/L 7

Neuraxial Administration

• TXA is not approved and not recommended for neuraxial (intrathecal) administration - inadvertent intrathecal administration has caused serious adverse reactions including seizures and cardiac arrhythmias 1

Important Clinical Pitfalls

Common Misconceptions

• The thrombotic risk in general surgical and trauma populations is not increased - meta-analyses of 125,550 participants found no evidence of increased thromboembolic complications when TXA is used appropriately 3, 5
• However, high-dose IV TXA (≥4g/24h) is associated with increased rates of DVT (RR 2.10), PE (RR 1.78), and seizures (RR 1.73) 4

Combination Therapy Restrictions

• Combination therapy with recombinant Factor VIIa and aPCC should be restricted to life- or limb-threatening bleeds due to estimated rate of arterial thrombosis and thromboembolic complications 3

Oral Contraceptive Use

• Use with extreme caution in patients on oral contraceptive pills due to thrombotic concerns 3
• Women taking tranexamic acid for menorrhagia had a 3-fold higher risk of developing deep vein thrombosis in one case-control study, though the confidence interval was wide (0.7 to 15.8) 8