Exposure-Response Relationship of Tranexamic Acid in Cardiac Surgery.
Research article published in Anesthesiology (2021)
Abstract
BACKGROUND: It is unclear whether high-dose regimens of tranexamic acid in cardiac surgery (total dose, 80 to 100 mg/kg) confer a clinical advantage over low-dose regimens (total dose, approximately 20 mg/kg), particularly as tranexamic acid-associated seizure may be dose-related. The authors' aim was to characterize the exposure-response relationship of this drug. METHODS: Databases were searched for randomized controlled trials of intravenous tranexamic acid in adult patients undergoing cardiopulmonary bypass surgery. Observational studies were added for seizure assessment. Tranexamic acid concentrations were predicted in each arm of each study using a population pharmacokinetic model. The exposure-response relationship was evaluated by performing a model-based meta-analysis using nonlinear mixed-effect models. RESULTS: Sixty-four randomized controlled trials and 18 observational studies (49,817 patients) were included. Seventy-three different regimens of tranexamic acid were identified, with the total dose administered ranging from 5.5 mg/kg to 20 g. The maximum effect of tranexamic acid for postoperative blood loss reduction was 40% (95% credible interval, 34 to 47%), and the EC50 was 5.6 mg/l (95% credible interval, 0.7 to 11 mg/l). Exposure values with low-dose regimens approached the 80% effective concentration, whereas with high-dose regimens, they exceeded the 90% effective concentration. The predicted cumulative blood loss up to 48 h postsurgery differed by 58 ml between the two regimens, and the absolute difference in erythrocyte transfusion rate was 2%. Compared to no tranexamic acid, low-dose and high-dose regimens increased the risk of seizure by 1.2-fold and 2-fold, respectively. However, the absolute risk increase was only clinically meaningful in the context of prolonged open-chamber surgery. CONCLUSIONS: In cardiopulmonary bypass surgery, low-dose tranexamic acid seems to be an appropriate regimen for reducing bleeding outcomes. This meta-analysis has to be interpreted with caution because the results are observational and dependent on the lack of bias of the predicted tranexamic acid exposures and the quality of the included studies.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Summary
It is unclear whether high-dose regimens of tranexamic acid in cardiac surgery (total dose, 80 to 100 mg/kg) confer a clinical advantage over low-dose regimens (total dose, approximately 20 mg/kg), particularly as tranexamic acid-associated seizure may be dose-related. The authors' aim was to characterize the exposure-response relationship of this drug.
Why This Matters for Hirudotherapy
This model-based meta-analysis pooled 64 randomized controlled trials and 18 observational studies (49,817 patients) using a population-pharmacokinetic model to characterize the exposure-response of the antifibrinolytic tranexamic acid in cardiac surgery, finding a maximum postoperative blood-loss reduction of about 40% with low-dose regimens already approaching near-maximal effect (predicted cumulative blood loss differing by only 58 mL between low- and high-dose regimens, with a 2% absolute difference in erythrocyte-transfusion rate), while high-dose roughly doubled seizure risk versus a 1.2-fold increase for low-dose, supporting low-dose regimens. For hirudotherapy this is relevant as a contrast case on the bleeding-versus-fibrinolysis axis: tranexamic acid suppresses fibrinolysis to reduce bleeding, the opposite pole from leech secretome molecules (such as destabilase and hirudin) that promote anticoagulation and clot breakdown, illustrating how finely dose and exposure govern the hemostatic balance leech therapy also perturbs. Caveat: the authors explicitly warn the results are model-derived and partly observational, with predicted (not measured) drug exposures, and the study concerns a synthetic antifibrinolytic in surgery, with no leech or hirudotherapy content.
Citation
Exposure-Response Relationship of Tranexamic Acid in Cardiac Surgery.
Zufferey PJ et al. · Anesthesiology, 2021
Added to ASH library: May 28, 2026 · Site last updated: June 18, 2026