What are the contraindications for Tranexamic acid (TXA)?

Contraindications for Tranexamic Acid

Tranexamic acid has three absolute contraindications: active intravascular clotting, subarachnoid hemorrhage, and hypersensitivity to tranexamic acid. 1

Absolute Contraindications

Active Intravascular Clotting

• TXA is absolutely contraindicated in patients with active intravascular clotting or disseminated intravascular coagulation (DIC), as it is an antifibrinolytic agent that can worsen thrombotic complications in this setting 1
• The guideline for cancer-associated DIC specifically recommends against routine use of TXA in non-hyperfibrinolytic DIC, as it may be deleterious 2

Subarachnoid Hemorrhage

• TXA is absolutely contraindicated in patients with subarachnoid hemorrhage, as anecdotal experience indicates it may cause cerebral edema and cerebral infarction 1

Hypersensitivity

• TXA is contraindicated in patients with known hypersensitivity to tranexamic acid or any of its ingredients, including those with history of anaphylactic reactions 1

Relative Contraindications and High-Risk Situations Requiring Extreme Caution

Recent Thrombotic Events

• Use TXA with extreme caution in patients with recent stroke or active thromboembolic disease, as these patients are at elevated risk for precipitated thrombosis 3, 4
• However, importantly, a history of prior venous thromboembolism (remote DVT or PE) is NOT a contraindication - multiple large studies demonstrate TXA safety in these patients 5, 6, 7

Massive Hematuria

• Use with extreme caution in patients with massive hematuria due to risk of ureteric obstruction from clot formation 3, 4

Oral Contraceptive Use

• Exercise caution when administering TXA to patients on oral contraceptive pills due to increased baseline thrombosis risk 3

Concomitant Prothrombotic Medications

• Avoid concomitant use with Factor IX Complex concentrates, Anti-inhibitor Coagulant concentrates, and hormonal contraceptives, as the risk of thrombosis may be increased 1
• The guideline for acquired hemophilia specifically states that TXA is contraindicated in conjunction with activated prothrombin complex concentrate (aPCC) administration 2

Specific Clinical Scenarios Where TXA Should NOT Be Used

Gastrointestinal Bleeding

• High-dose IV TXA (≥4g/24h) should NOT be used in critically ill patients with gastrointestinal bleeding, as the HALT-IT trial demonstrated increased rates of DVT (RR 2.10), PE (RR 1.78), and seizures (RR 1.73) without mortality benefit 2, 3

Cancer-Related DIC (Non-Hyperfibrinolytic)

• TXA should NOT be routinely used in cancer-related DIC except in hyperfibrinolytic DIC with therapy-resistant bleeding, as it may worsen thrombotic complications 2

Mandatory Dose Adjustments (Not Contraindications)

Renal Impairment

• TXA requires dose reduction in renal dysfunction as it is renally excreted and accumulates in renal failure 3, 1
• For serum creatinine 1.36-2.83 mg/dL: reduce to 10 mg/kg twice daily 1
• For serum creatinine 2.83-5.66 mg/dL: reduce to 10 mg/kg daily 1
• For serum creatinine >5.66 mg/dL: reduce to 10 mg/kg every 48 hours or 5 mg/kg every 24 hours 1

Important Clinical Pitfalls to Avoid

• Do not withhold TXA from patients with remote history of VTE - extensive evidence demonstrates safety in this population 5, 6, 7
• Do not confuse "history of thromboembolism" with "active intravascular clotting" - only the latter is an absolute contraindication 1
• Ensure correct route of administration - inadvertent intrathecal administration has caused seizures and cardiac arrhythmias 1
• Do not exceed 100 mg/kg total dose, particularly in cardiac surgery, due to seizure risk at higher doses 3, 8