What are the negative implications of Tranexamic Acid (TXA)?

From the Guidelines

Tranexamic acid (TXA) is generally safe to use, with no evidence of an increased risk of thromboembolic complications associated with its use, as supported by a meta-analysis of 216 trials 1.

Key Points to Consider

• The medication has been proven to reduce bleeding in most surgical settings, including cardiac and major non-cardiac surgery, major trauma, and postpartum hemorrhage 1.
• However, it is essential to use TXA with caution in patients, especially those with a history of thromboembolism or at high risk for thrombosis.
• A meta-analysis focusing on patients undergoing non-cardiac surgery found no evidence of an increased risk of cardiovascular thromboembolic complications, seizures, or mortality at 30 days with TXA use 1.
• Some studies have noted increased rates of deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as seizures, though the absolute number of these events was very small 1.

Important Considerations for Use

• Patients with subarachnoid hemorrhage should avoid TXA, as it may increase the risk of cerebral edema and infarction.
• Dose adjustment is necessary in patients with renal impairment, as TXA is primarily eliminated through the kidneys, and accumulation can lead to toxicity.
• Common side effects include gastrointestinal disturbances, hypotension with rapid IV administration, and visual disturbances like color vision changes.

Recommendation

Based on the most recent and highest-quality evidence 1, TXA can be used safely in most clinical settings, but it is crucial to carefully evaluate the patient's risk factors and medical history before administration. Some key points to consider when using TXA include:

• Careful patient selection and evaluation of risk factors
• Close monitoring for potential side effects, such as thrombotic events and seizures
• Dose adjustment in patients with renal impairment
• Avoidance in patients with subarachnoid hemorrhage or those at high risk for thrombosis.

From the FDA Drug Label

5 WARNINGS AND PRECAUTIONS

5.1 Thromboembolic Risk Tranexamic acid is contraindicated in patients with active intravascular clotting. Tranexamic acid is an antifibrinolytic and may increase the risk of thromboembolic events. Venous and arterial thrombosis or thromboembolism has been reported in patients treated with tranexamic acid Avoid concomitant use of tranexamic acid and medical products that are pro-thrombotic, as the risk of thrombosis may be increased.

5.2 Risk of Medication Errors Due to Incorrect Route of Administration Tranexamic acid is for intravenous use only. Serious adverse reactions including seizures and cardiac arrythmias have occurred when tranexamic acid was inadvertently administered intrathecally instead of intravenously

5.3 Seizures Tranexamic acid may cause seizures, including focal and generalized seizures.

5.4 Hypersensitivity Reactions Cases of hypersensitivity reactions, including anaphylactic reactions, have occurred with use of intravenous tranexamic acid.

5.5 Visual Disturbances Although not seen in humans, focal areas of retinal degeneration have been observed in cats and dogs following oral or intravenous tranexamic acid at doses between 250 to 1600 mg/kg/day (1.6 to 22 times the recommended usual human dose based on body surface area) from 6 days to 1 year.

5.6 Dizziness Tranexamic acid may cause dizziness.

The negative implications of Tranexamic Acid (TXA) include:

• Thromboembolic Risk: increased risk of thromboembolic events, including venous and arterial thrombosis or thromboembolism 2
• Seizures: may cause seizures, including focal and generalized seizures 2
• Hypersensitivity Reactions: cases of hypersensitivity reactions, including anaphylactic reactions, have occurred with use of intravenous tranexamic acid 2
• Visual Disturbances: potential risk of retinal degeneration, although not seen in humans 2
• Dizziness: may cause dizziness, which can be worsened by concomitant use of other drugs that may also cause dizziness 2
• Medication Errors: risk of serious adverse reactions, including seizures and cardiac arrythmias, due to incorrect route of administration 2

From the Research

Negative Implications of Tranexamic Acid (TXA)

• The use of TXA has been associated with an increased risk of seizures, particularly at high doses 3, 4.
• There is a potential risk of thrombosis with TXA, although the evidence is not consistent across all studies 5, 6.
• Some studies have reported an increased risk of thrombotic events with TXA, particularly in patients with a history of thromboembolism 6.
• High doses of TXA may increase the risk of seizures, particularly in patients with brain injury or cardiac surgery 3, 4.
• Delayed administration of TXA for trauma events or postpartum hemorrhage may increase mortality 4.

Specific Patient Populations

• In patients undergoing cranial neurosurgery, TXA does not appear to increase the risk of venous thromboembolic events (VTEs) 7.
• In pediatric patients undergoing craniosynostosis procedures, low dosing protocols of TXA should be used due to the lack of studies on high dose TXA in children 7.
• In patients with bleeding disorders or taking antithrombotic drugs, TXA may be effective in reducing bleeding, but the optimal dose and timing need to be determined 4.

Dosage and Timing

• The optimal dose and timing of TXA to minimize the risk of seizures or thromboembolic events is still being researched 3, 4.
• High doses of TXA should be avoided due to the increased risk of seizures 3.
• The dosage and timing of TXA may vary depending on the specific clinical indication and patient population 4.