BACKGROUND:
Tranexamic acid (TXA) is effective in reducing blood loss in total joint arthroplasty (TJA), but concerns still remain regarding the drug's safety. The purpose of this direct meta-analysis was to evaluate and establish a basis for the safety recommendations of the combined clinical practice guidelines on the use of TXA in primary TJA.

METHODS:
A search was completed for studies published before July 2017 on TXA in primary TJA. We performed qualitative and quantitative homogeneity testing and a direct comparison meta-analysis. We used the American Society of Anesthesiologists (ASA) score of 3 or greater as a proxy for patients at higher risk for complications in general and performed a meta-regression analysis to investigate the influence of comorbidity burden on the risk of arterial thromboembolic event and venous thromboembolic event (VTE).

RESULTS:
Topical, intravenous, and oral TXA were not associated with an increased risk of VTE after TJA. In addition, meta-regression demonstrated that TXA use in patients with an ASA status of 3 or greater was not associated with an increased risk of VTE after total knee arthroplasty.

CONCLUSION:
Although most studies included in our analysis excluded patients with a history of prior thromboembolic events, our findings support the lack of evidence of harm from TXA administration in patients undergoing TJA. Moderate evidence supports the safety of TXA in patients undergoing total knee arthroplasty with an ASA score of 3 or greater. The benefits of using TXA appear to outweigh the potential risks of thromboembolic events even in patients with a higher comorbidity.