Purpose: To investigate the difference in blood loss between two injection methods, intravenous (IV) and intra-articular (IA) methods via drain tube. Materials and Methods: A total of 183 patients who underwent total knee arthroplasty between October 2013 and March 2016 were included. The method of tranexamic acid (TXA) administration was intravenously injected before August 2015, and it was applied thereafter to the joint through a drainage tube post intra-articular suture. Our subjects were

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... vided into the following groups: The intravenous unilateral (IVU), intravenous bilateral (IVB), intra-articular unilateral (IAU), and intra-articular bilateral (IAB) groups. Hemoglobin and hematocrit, drainage amount, transfusion frequency, mean transfusion volume, and blood loss, as well as complications were compared between the groups. Results: Drainage amount was 558.08±296.29 ml in IVU, and 498.39±199.70 ml in IAU; there was less drainage in IAU than in IVU, but without significance (p=0.262). Moreover, the drainage amount was 1,110.39±396.23 ml in IVB and 827.14±282.47 ml in IAB, which was significantly lower in IAB (p=0.000). Transfusion frequency was 5 patients (10.0%) in IVU and 2 patients (4.5%) in IAU, but without significant difference (p=0.442). Moreover, the frequency was 16 patients (29.6%) in IVB and 1 patient (2.9%) in IAB, which was significantly lower in the IAB group (p=0.002). Mean transfusion volume was 44.80±144.71 ml in IVU and 21.80±106.86 ml in IAU, but without significant difference (p=0.389); the volume was 177.80±321.00 ml in IVB and 18.30±108.18 ml in IAB, with statistical significance (p=0.001). Blood loss was 1,318.70±724.20 ml in IVU and 963.28±454.03 ml in IAU, which was significantly lower in the IAU (p=0.006); blood loss was 1,837.40±699.70 ml in IVB, and 1,337.60±382.20 ml in IAB and it was significantly lower in IAB (p=0.000). Complications included deep vein thrombosis in one case in IVU. Conclusion: In TKA, IA injection of TXA significantly reduced blood loss compared with IV injection, especially in bilateral TKA.