Is Combined Tranexamic Acid Administration Superior to Single-Route Protocols in Primary Total Knee Arthroplasty? A Prospective Cohort Study

Background: The optimal route of tranexamic acid (TXA) administration remains one of the most debated topics in total knee arthroplasty. This study aimed to compare the effects of intravenous (IV), intra-articular (IA), and combined TXA protocols on total blood loss (TBL) and hidden blood loss (HBL), while identifying independent predictors of perioperative bleeding. Methods: In a prospective cohort study of 245 patients undergoing primary TKA, participants were assigned into four groups: IV TXA (15 mg/kg), IA TXA (1 g), combined (IV + IA), and a control group. TBL and HBL were calculated using the Gross formula. A multivariate linear regression model was used to assess independent associations of each protocol. Results: The IV group demonstrated significantly lower TBL (mean 898 mL) and HBL (mean 568 mL) compared with both the control (1329 mL and 894 mL; p = 0.002) and IA groups (1129 mL and 748 mL; p = 0.008). While IA TXA reduced 24 h drain output (p < 0.001), it did not significantly reduce TBL (p = 0.539) or HBL (p = 0.875). No significant differences were found between the IV-only and combined groups (p > 0.05). Multivariate regression identified the IV route as an independent predictor of reduced TBL (B = −383.7, p = 0.001). Conclusion: A single intravenous dose of TXA was associated with lower total and hidden blood loss compared with intra-articular administration. The lack of additional benefit in the combined group suggests a possible plateau effect of systemic administration, which is hypothesis-generating and limited by the study design for blood conservation in TKA. Level of Evidence: Level II, Prospective Cohort Study.