Administration Method Versus Placebo
Administration of intravenous (IV), topical, and oral TXA as well as combinations of individual formulations of TXA are all effective strategies when compared to placebo for reducing calculated blood loss and the need for transfusion during the perioperative episode of a primary TJA.
Tranexamic Acid in Total Joint Arthroplasty
Developed by the American Association of Hip and Knee Surgeons

Rationale
The direct meta-analysis of one moderate quality and 82 high quality studies provided significant evidence for the ability of TXA to reduce the risk of blood loss and need for transfusion during the perioperative episode of primary hip and knee arthroplasties. 2, 3 Subsequent network meta-analysis supported the blood-sparing properties of TXA. 2, 3

Total Hip Arthroplasty
Intravenous and topical TXA have been shown with limited heterogeneity in direct metaanalysis to reduce blood loss.2 Similarly, IV and topical TXA were found to reduce the risk of transfusion compared to placebo by 60% and 71%, respectively.2 Network metaanalysis of low dose IV (< 20mg/kg or ≤ 1g), high dose IV (≥ 20mg/kg or > 1g), high dose topical (> 1.5g), oral, and combined IV/topical TXA reduced the risk for blood loss compared to placebo.2 Correspondingly, network meta-analysis demonstrated low dose IV, high dose IV, high dose topical, low dose topical, and combined IV/topical TXA to significantly reduce the risk of transfusion.2

Due to a lack of studies directly comparing oral TXA with placebo, no conclusions could be derived in the direct meta-analysis.2 Network meta-analysis was performed to provide an indirect comparison of oral TXA, which demonstrated significantly reduced blood loss compared to placebo.2 Although oral TXA was shown to be equivalent regarding risk of transfusion to all other formulations of TXA in the network meta-analysis, oral TXA did not reduce the risk of transfusion compared to placebo. The inconsistency is the result of the network relying on indirect comparisons and a limited number of studies. Similar limitations were observed for lower doses (≤ 1.5g) of topical TXA in the network meta-analysis.2 In the analysis, low dose topical TXA did not significantly reduce blood loss but did reduce the risk of transfusion compared to placebo.2

Total Knee Arthroplasty
Intravenous and topical TXA consistently demonstrated in direct meta-analysis the ability to reduce blood loss during the perioperative episode of a primary TKA.3 Topical and oral TXA reduced the risk of transfusion by 66% and 61% for each respective formulation of TXA when compared to placebo.3 Intravenous TXA administered as a single dose either before or after incision, reduced the risk of transfusion by either 81% or 55% compared to placebo.3 When multiple doses of IV TXA were administered, the observed reduction in transfusion was 75% compared to placebo.3 Subsequent network meta-analysis demonstrated low dose IV, high dose IV, low dose topical, high dose topical, and oral TXA as well as combinations of IV/topical and IV/oral TXA to reduce blood loss and risk of transfusion during the perioperative episode of a TKA.3

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