Comment on “Equivalence of oral and intravenous tranexamic acid in knee arthroplasty: a systematic review and meta-analysis of randomized clinical trials”

Dear Editor, We read with considerable interest the systematic review and meta-analysis by Luo et al evaluating the equivalence of oral and intravenous tranexamic acid in knee arthroplasty[1]. By restricting inclusion to randomized controlled trials and focusing exclusively on knee procedures, the authors address an important methodological limitation of prior analyses that pooled hip and knee arthroplasty, thereby improving procedural homogeneity and strengthening the validity of their conclusions. This manuscript was prepared in line with the TITAN 2025 guidelines[2] on artificial intelligence use and transparency. The findings demonstrate comparable effects of oral and intravenous tranexamic acid on perioperative hemoglobin change, transfusion rates, complications, and length of hospital stay. These results are clinically meaningful, particularly in the context of enhanced recovery protocols, where simplicity of administration, workflow efficiency, and cost containment are increasingly emphasized. Oral tranexamic acid therefore appears to represent a pragmatic alternative to intravenous administration in routine knee arthroplasty practice. Several considerations, however, merit further discussion. Perioperative blood loss is a dynamic process that extends beyond conventional laboratory indices. None of the included trials systematically evaluated hidden blood loss, postoperative inflammatory response, or fibrinolytic activity, which may differ subtly according to the route and timing of administration. Such differences, although not reflected in hemoglobin values, may influence early postoperative pain, swelling, and functional recovery[3,4]. Incorporating these parameters in future studies could provide a more comprehensive assessment of clinical equivalence. In addition, substantial variability existed in dosing regimens and administration timing across the included trials. Oral tranexamic acid relies on predictable gastrointestinal absorption and precise preoperative timing to achieve therapeutic plasma concentrations, whereas intravenous administration permits greater intraoperative flexibility. The absence of pharmacokinetically guided protocols limits direct comparability between studies. Future randomized trials would benefit from standardized, physiology informed dosing strategies that account for tourniquet use, operative duration, body weight, and renal function[5,6]. Patient selection also warrants attention. Although thromboembolic complications were uncommon, many trials excluded individuals with significant cardiovascular disease, prior venous thromboembolism, or renal impairment. As oral tranexamic acid is increasingly adopted as a routine alternative, evidence supporting its safety and efficacy in higher risk populations remains limited. Pragmatic trials or stratified analyses reflecting real world patient profiles would enhance the generalizability of current evidence[7]. Finally, the clinical impact of tranexamic acid administration should not be confined to short term hematologic outcomes. Measures such as early mobilization, patient reported outcome scores, and longer term functional recovery are increasingly prioritized in contemporary arthroplasty research but remain insufficiently explored in comparative tranexamic acid studies. In summary, the work by Luo et al provides robust knee specific evidence supporting oral tranexamic acid as an effective alternative to intravenous administration. Extending this research to include pharmacokinetic standardization, broader patient inclusion, and functional outcome assessment may further refine perioperative blood management strategies and promote more individualized care in knee arthroplasty.