Is there high-quality evidence that tranexamic acid (TXA) increases the risk of thrombotic events?

From the Guidelines

No, there is no high-quality evidence that tranexamic acid (TXA) significantly increases the risk of thrombotic events when used appropriately. Multiple large randomized controlled trials and meta-analyses, such as the one mentioned in the association of anaesthetists guidelines 1, have consistently shown that TXA does not substantially increase the risk of venous thromboembolism (VTE), myocardial infarction, stroke, or other thrombotic complications compared to placebo. This safety profile has been demonstrated across various clinical settings including trauma, postpartum hemorrhage, and elective surgeries. Some studies, like the one referenced in the EASL clinical practice guidelines 1, suggest a potential increased risk of thrombotic events in specific patient populations, such as those with cirrhosis and variceal bleeding, but these findings are not generalizable to all patients receiving TXA. The CRASH-2 trial, which included over 20,000 trauma patients, found no increase in vascular occlusive events with TXA use 1. Similarly, other trials have shown no increased thrombotic risk with TXA use. TXA works by inhibiting fibrinolysis (the breakdown of blood clots) rather than directly promoting clot formation, which may explain why it doesn't substantially increase thrombotic risk despite its hemostatic effects. However, caution is still warranted in patients with pre-existing high thrombotic risk factors, and TXA should be used at appropriate doses and durations as recommended for specific clinical scenarios. The typical adult dose ranges from 1-2 grams IV for acute bleeding to 10-25 mg/kg IV every 8 hours for ongoing bleeding risk, depending on the clinical context. Key points to consider when using TXA include:

• Early administration is crucial, with the best outcomes seen when TXA is given within 3 hours of injury 1
• Appropriate dosing and duration of treatment are essential to minimize potential risks and maximize benefits
• Patients with pre-existing high thrombotic risk factors require careful consideration and monitoring when receiving TXA.

From the FDA Drug Label

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. Inform patients that tranexamic acid may increase the risk of venous and arterial thrombosis or thromboembolism and to contact their healthcare provider for any signs or symptoms suggestive of thromboembolism

The high-quality evidence suggests that tranexamic acid may increase the risk of thrombotic events, including venous and arterial thrombosis or thromboembolism 2. Key points to consider include:

• Concomitant use of pro-thrombotic medical products may further increase this risk 2
• Patient counseling should include information about the potential increased risk of thromboembolism 2 It is essential to weigh the benefits and risks of tranexamic acid treatment and to monitor patients closely for signs and symptoms of thromboembolic events.

From the Research

Tranexamic Acid and Clot Risk

• The relationship between tranexamic acid (TXA) and the risk of thrombotic events has been investigated in several studies 3, 4, 5, 6, 7.
• A study published in 2013 found that TXA may expose patients to a risk of thrombosis, particularly in situations with minor bleeding 3.
• However, a review of TXA use in surgery and other indications published in 1999 found no increased risk of thrombosis with the drug 4.
• Case reports have described instances of pulmonary embolism associated with TXA use 5, 7.
• A systematic review and meta-analysis published in 2021 found no evidence that TXA increases the risk of thrombotic events, but noted a potential dose-dependent increase in the risk of seizures 6.

Study Findings

• A case-control study using data from the British General Practice Research Database found a 3-fold higher risk of developing deep vein thrombosis in women taking TXA, but the confidence interval was wide and a major increase in risk could not be ruled out 3.
• A meta-analysis of 60 trials found that TXA reduced the number of patients requiring allogeneic blood transfusions after cardiac surgery with cardiopulmonary bypass, but did not report an increased risk of thrombosis 4.
• A systematic review and meta-analysis of 234 studies with 102,681 patients found no evidence that TXA increased the risk of thrombotic events, but found a potential dose-dependent increase in the risk of seizures 6.

Clinical Implications

• The harm-benefit balance of TXA is favorable in severe traumatic bleeding, but the thrombotic risk is poorly documented in situations with minor bleeding 3.
• TXA is well tolerated, with nausea and diarrhea being the most common adverse events, but the risk of thrombosis and seizures should be considered in clinical practice 4, 6.