Background: The literature is inconclusive regarding the potential complications of tranexamic acid (TXA), an antifibrinolytic drug, for total hip arthroplasty (THA). The purpose of this study is to compare complication rates and patient outcomes between THA patients administered TXA vs. THA patients not administered TXA. Methods: The TriNetX Research network was utilized to generate a cohort of adult patients who underwent THA between 2003 and 2024. These patients were categorized into two subgroups for the retrospective analysis: (1) patients who received TXA 24 h prior to THA (TXA), and (2) patients who did not receive TXA 24 h prior to total hip arthroplasty (no-TXA). The follow-up period was 30 and 90 days. Results: At 30 days following THA, the TXA patients had a reduced risk of transfusion (risk ratio (RR): 0.412; 95% confidence intervals (CI): 0.374, 0.453), reduced risk of DVT (RR: 0.856; CI: 0.768, 0.953), reduced risk of joint infection (RR: 0.808; CI: 0.710, 0.920), but a higher rate of periprosthetic fracture (RR: 1.234; CI: 1.065, 1.429) compared to patients who did not receive TXA. At 90 days following THA, TXA patients had a reduced risk of transfusion (RR: 0.446; CI: 0.408, 0.487), DVT (RR: 0.847; CI: 0.776, 0.924), and periprosthetic joint infection (RR: 0.894; CI: 0.815, 0.982) compared to patients who did not receive TXA. Patients who received TXA had higher rates of periprosthetic fracture (RR: 1.219; CI: 1.088, 1.365), acute postoperative anemia (RR: 1.222; CI: 1.171, 1.276), deep surgical site infection (SSI) (RR: 1.706; CI: 1.117, 2.605), and superficial SSI (RR: 1.950; CI: 1.567, 2.428) compared to patients who did not receive TXA. Conclusions: Patients receiving TXA prior to THA exhibited significantly reduced the prevalence of blood transfusions, DVT, and periprosthetic joint infection following THA. However, superficial SSI and periprosthetic fracture were seen with higher rates in the TXA cohort than in the no-TXA cohort.
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