Does tranexamic acid (TXA) increase the risk of venous thromboembolism (VTE) or venous congestion?

Does Tranexamic Acid Increase the Risk of Venous Thromboembolism?

The risk of venous thromboembolism (VTE) with tranexamic acid depends critically on the clinical context: TXA does NOT increase VTE risk in trauma, surgery, or postpartum hemorrhage when used at standard doses within 3 hours, but it approximately doubles VTE risk in patients with gastrointestinal bleeding, particularly those with liver disease. 1

Context-Specific VTE Risk Profile

High-Risk Scenario: Gastrointestinal Bleeding with Liver Disease

• In the HALT-IT trial of 12,009 patients with acute upper GI bleeding (50% suspected variceal bleeding), TXA caused an almost 2-fold increase in venous thromboembolic events compared to placebo. 1

• The VTE risk was concentrated specifically in the subgroup with comorbid liver disease and suspected variceal bleeding, likely related to the relative hypofibrinolysis already present in acute-on-chronic liver failure. 1

• The European Association for the Study of the Liver explicitly recommends AGAINST routine TXA use in variceal bleeding based on this evidence, noting no mortality benefit and increased thrombotic complications. 1

Low-Risk Scenarios: Trauma, Surgery, and Postpartum Hemorrhage

• A meta-analysis of 216 trials including 125,550 participants found no evidence of increased thromboembolic complications with TXA (risk difference = 0.001; 95% CI, -0.001 to 0.002; P = 0.49) across diverse surgical settings. 2

• In trauma patients specifically, the landmark CRASH-2 trial (>20,000 patients) demonstrated no increase in VTE, stroke, or myocardial infarction with standard-dose TXA. 2

• A 2025 meta-analysis of 191 randomized controlled trials in non-cardiac surgery (40,621 participants) confirmed no increased cardiovascular thromboembolic complications, seizures, or mortality. 2

Critical Dosing Distinction

The dose of TXA determines thrombotic risk:

• Standard trauma/surgical dosing (1g IV over 10 minutes, followed by 1g over 8 hours) carries minimal VTE risk. 2

• High-dose regimens (≥4g/24h) used in the GI bleeding trials significantly increase DVT risk (RR 2.10), PE risk (RR 1.78), and seizure risk (RR 1.73) without mortality benefit. 2

Contradictory Research Evidence Requiring Interpretation

While guideline-level evidence shows no VTE increase in appropriate populations, several observational studies report conflicting findings:

• A 2019 single-center propensity-matched study found TXA associated with >3-fold increased VTE odds (aOR 3.3; 95% CI 1.3-9.1) in trauma patients. 3

• A 2015 study in hip arthroplasty without chemical prophylaxis showed increased distal DVT (18.9% vs 9.4%, p<0.05) but no increase in proximal DVT or PE. 4

• However, a 2023 multicenter CLOTT study of 7,331 trauma patients found TXA was NOT independently associated with VTE in adjusted analyses (aHR 1.00,95% CI 0.69-1.46), despite higher baseline VTE rates in the TXA group due to injury severity. 5

• A 2024 analysis of 70,759 high-risk arthroplasty patients with prior VTE history found TXA did NOT increase PE (aOR 0.90), stroke (aOR 0.97), or MI (aOR 0.93) risk. 6

The weight of high-quality evidence (large RCTs and meta-analyses) supersedes these observational studies, which suffer from confounding by indication—sicker patients receive TXA.

FDA-Labeled Warnings

The FDA label for TXA states: 7

• "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 with pro-thrombotic agents including Factor IX concentrates, anti-inhibitor coagulant concentrates, and hormonal contraceptives. 7

• TXA is contraindicated in patients with active intravascular clotting. 7

Clinical Decision Algorithm

For trauma/major surgical bleeding:

• Administer standard-dose TXA (1g loading, 1g maintenance) within 3 hours without VTE concern in patients without active thrombosis. 2
• Ensure chemical DVT prophylaxis is initiated once hemostasis achieved. 5

For GI bleeding:

• Do NOT use TXA routinely—reserve only for hereditary hemorrhagic telangiectasia with chronic bleeding (500mg BID titrated to 1000mg QID). 8
• If liver disease present, TXA is particularly hazardous for VTE. 1

For patients on oral contraceptives or with prior VTE:

• TXA remains safe in surgical/trauma contexts based on large-scale evidence, but use caution and ensure adequate prophylaxis. 2, 6

Key Pitfall to Avoid

Do not extrapolate the safety data from trauma/surgery to GI bleeding populations—the mechanism of bleeding, underlying coagulopathy, and patient risk profile are fundamentally different. 1, 8 The hypofibrinolytic state in cirrhosis makes antifibrinolytics both ineffective and prothrombotic. 1