Does tranexamic acid (TXA) increase the risk of Venous Thromboembolism (VTE)?

From the Guidelines

Tranexamic acid (TXA) does not significantly increase the risk of venous thromboembolism (VTE) when used appropriately in most clinical settings. Despite being an antifibrinolytic agent that inhibits clot breakdown, multiple large clinical trials and meta-analyses have consistently shown that TXA does not lead to higher rates of VTE complications compared to placebo, as evidenced by a meta-analysis of 216 trials (125,550 participants) that found no evidence of an increased risk of thromboembolic complications associated with the use of tranexamic acid 1. When administered for acute bleeding, trauma, or perioperative hemorrhage prevention, the standard dosing has demonstrated a favorable safety profile. However, caution is warranted in patients with pre-existing high thrombotic risk factors such as history of previous VTE, known thrombophilia, or active cancer. In these high-risk populations, the benefits of reducing bleeding must be carefully weighed against theoretical thrombotic concerns.

Some studies have suggested a potential increased risk of VTE with TXA in specific populations, such as patients with cirrhosis and active variceal bleeding, where a large randomized placebo-controlled trial found an almost 2-fold increase in the incidence of venous thromboembolic events in the tranexamic acid group compared to the placebo group 1. However, this finding is not generalizable to most clinical settings where TXA is used. The mechanism behind the reassuring safety profile of TXA likely relates to its specific action on the fibrinolytic system rather than on primary clot formation pathways. TXA works by inhibiting plasminogen activation, which prevents excessive clot breakdown but does not actively promote new clot formation in the venous system.

Key points to consider when using TXA include:

• TXA has a favorable safety profile in most clinical settings
• Caution is warranted in patients with pre-existing high thrombotic risk factors
• The benefits of reducing bleeding must be carefully weighed against theoretical thrombotic concerns in high-risk populations
• The mechanism of action of TXA is specific to the fibrinolytic system and does not promote new clot formation in the venous system.

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.

Tranexamic acid may increase the risk of Venous Thromboembolism (VTE), as it is an antifibrinolytic and has been associated with thromboembolic events, including venous and arterial thrombosis or thromboembolism. Key points to consider:

• Tranexamic acid is contraindicated in patients with active intravascular clotting.
• The risk of thrombosis may be increased with concomitant use of pro-thrombotic medical products. 2 2

From the Research

Evidence for Tranexamic Acid and Venous Thromboembolism (VTE) Risk

• The relationship between tranexamic acid (TXA) and the risk of Venous Thromboembolism (VTE) has been investigated in several studies, yielding mixed results.
• A study from 2015 3 found that TXA statistically significantly increased the incidence of total deep vein thrombosis (DVT) on post-operative day 7 compared to a control group, although most cases were isolated distal DVT.
• In contrast, a 2024 study 4 concluded that TXA did not increase the risk of postoperative pulmonary embolism, stroke, or myocardial infarction in patients with a history of VTE undergoing total joint arthroplasty.
• Another 2024 study 5 suggested that TXA does not appear to increase the risk for VTE when used as indicated in select patients undergoing nontraumatic cranial neurosurgery procedures.

Studies Indicating Increased Risk

• A 2019 study 6 found that TXA administration was associated with an increased risk of posttraumatic VTE, with more than a threefold increase in the odds of VTE.
• An earlier study from 2009 7 indicated that recent use of TXA might be associated with an increased risk of VTE, although the risk estimate did not reach statistical significance.

Variability in Findings

• The variability in findings across studies may be due to differences in patient populations, surgical procedures, and TXA dosing protocols.
• Further research is needed to fully understand the relationship between TXA and VTE risk, particularly in high-risk patient groups.