What is the Ideal Route of Administration of Tranexamic Acid in TKA? A Randomized Controlled Trial

Background TKA commonly involves substantial blood loss and tranexamic acid has been used to reduce blood loss after TKA. Numerous clinical trials have documented the efficacy and safety of intravenous (IV) or intraarticular (IA) use of tranexamic acid. Combined administration of tranexamic acid also has been suggested; however, there is no consensus regarding the ideal route of tranexamic acid administration.

Questions/Purposes (1) To compare the efficacy of tranexamic acid in terms of total blood loss and the allogeneic transfusion rate among three routes of administration: IV alone, IA alone, and combined IV and IA. (2) To compare these regimens in terms of venous thromboembolism (VTE) and the frequency of wound complications.

Methods In total, 376 patients undergoing TKA between March 2014 and March 2015 were randomized to four groups by the route of tranexamic acid administration: IV only, IA only, low-dose combined (IV + IA injection of 1 g), and high-dose combined (IV + IA injection of 2 g). The calculated total blood loss, allogeneic transfusion rate, decrease in hemoglobin, the frequency of symptomatic deep vein thrombosis and pulmonary embolism, wound complications, and periprosthetic joint infection were compared among the groups. Total blood loss was calculated using estimated total body blood volume and hemoglobin loss. The decision regarding when to transfuse was determined based on preset criteria.

Results The high- and low-dose combined groups and the IA-only group had lower total blood loss (564 ± 242 mL, 642 ± 242 mL, and 633 ± 205 mL, respectively) than the IV-only group (764 ± 217 mL; mean differences = 199 mL [95% CI, 116-283 mL], p < 0.001; 121 mL [95% CI, 38-205 mL], p = 0.001; 131 mL [95% CI, 47-214 mL], p < 0.001); no differences were found among the other three groups. No patients in any study group received an allogeneic transfusion. One patient in the IV-only group had a symptomatic pulmonary embolism develop, but no other symptomatic VTE events occurred in any group. In addition, no differences were observed in wound complications, such as superficial wound necrosis (one patient in the IV-only and the high-dose combined group, respectively) and oozing (IV-only, IA-only, low-dose combined, high-dose combined = 3%, 4%, 4%, and 7%; p = 0.572) between the groups. No patients had a periprosthetic joint infection.

Conclusion IA tranexamic acid administration further reduces blood loss after TKA in comparison to IV use alone; no additional effect in further reducing blood loss was found in combination with IV tranexamic acid. Appropriately powered studies are needed to confirm the safety of this route of administration as the preferred route of administration in TKA.

Level of Evidence Level I, therapeutic study.