Efficacy and Safety of Intraosseous Regional Versus Intravenous Tranexamic Acid in Total Knee Arthroplasty: A Randomized Controlled Trial.

Background: Tranexamic acid (TXA) reduces perioperative blood loss in total knee arthroplasty (TKA); however, evidence for intraosseous regional administration (IORA) remains limited. We evaluated the efficacy and safety of IORA-TXA versus intravenous TXA (IV-TXA) in TKA. Methods: In this prospective, randomized, single-center trial, 98 patients undergoing primary TKA were randomized 1:1 to IORA-TXA or IV-TXA (49 per group) at a uniform dose of 20 mg/kg. The primary outcome was calculated perioperative blood loss. Secondary efficacy outcomes included calculated hidden blood loss, postoperative hemoglobin (Hb) levels, and transfusion rate. Safety outcomes included deep vein thrombosis (DVT), muscular calf vein thrombosis, pulmonary embolism (PE), and wound-related complications. Results: Compared with IV-TXA, IORA-TXA reduced calculated perioperative blood loss (674.8 ± 335.0 vs. 817.5 ± 357.2 mL; mean difference, 142.6 mL; 95% CI, 7.4-277.8; p = 0.038) and calculated hidden blood loss (644.8 ± 335.5 vs. 790.9 ± 339.0 mL; mean difference, 146.1 mL; 95% CI, 10.9-281.3; p = 0.035). Postoperative Hb was similar on POD1 (134.0 ± 9.8 vs. 130.1 ± 11.1 g/L; p = 0.067) but was higher with IORA-TXA on POD2 (119.8 ± 8.3 vs. 113.8 ± 11.5 g/L; mean difference 6.0 g/L; 95% CI 2.0-10.0; p = 0.005) and POD3 (114.8 ± 7.9 vs. 109.8 ± 12.6 g/L; mean difference 5.0 g/L; 95% CI 0.8-9.2; p = 0.020). No patient required blood transfusion. DVT detected by routine postoperative Doppler occurred numerically more often with IORA-TXA than with IV-TXA: 10.2% (95% CI, 3.4%-22.2%) versus 0.0% (95% CI, 0.0%-7.3%); p = 0.056. Conclusions: IORA-TXA reduced calculated perioperative and hidden blood loss and improved early postoperative Hb preservation compared with IV-TXA. However, DVT incidence was numerically higher with IORA-TXA, indicating a potential thromboembolic safety signal that warrants confirmation in larger, adequately powered trials. Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.