Tranexamic acid in primary total knee arthroplasty: a systematic review and meta-analysis of blood loss, transfusion, and deep vein thrombosis.

BACKGROUND

Tranexamic acid (TXA) has been widely used in primary total knee arthroplasty (TKA) to reduce perioperative blood loss, but the pooled evidence regarding blood loss, transfusion, and deep vein thrombosis (DVT) remains to be further clarified. The purpose of this meta-analysis was to evaluate the efficacy and safety of TXA in primary TKA.

METHODS

PubMed, Embase, Web of Science, the Cochrane Library, and relevant additional sources were searched to identify randomized controlled trials (RCTs) comparing TXA with a control regimen in primary unilateral TKA. The primary outcomes were blood loss, transfusion, and DVT. Continuous outcomes were pooled as mean differences (MDs) with 95% confidence intervals (CIs), and dichotomous outcomes were pooled as risk ratios (RRs) or odds ratios (ORs) with 95% CIs. Risk of bias was assessed using the Cochrane RoB 2 tool. Random-effects models were applied for meta-analysis. For the blood-loss outcome, an additional robustness analysis was performed using an empirical Bayes random-effects model with Knapp-Hartung standard error adjustment to evaluate whether the result was sensitive to model assumptions, given that methodological choices in random-effects meta-analysis may influence statistical significance when substantial heterogeneity is present.

RESULTS

A total of 17 studies were included in the systematic review and meta-analysis. TXA was associated with significantly reduced blood loss compared with control (MD = -423.28 mL, 95% CI -536.90 to -309.66; P < 0.001), although substantial heterogeneity was observed (I² = 93.44%). Leave-one-out sensitivity analysis showed that the pooled effect remained significant after exclusion of individual studies; exclusion of one influential study reduced heterogeneity to 81.88%. The Knapp-Hartung-adjusted robustness analysis yielded a similar significant effect estimate. TXA also significantly reduced transfusion risk (RR = 0.55, 95% CI 0.45 to 0.68; P < 0.001), with no significant heterogeneity (I² = 0.0%). No significant difference was found between the TXA and control groups in the incidence of DVT (OR = 0.75, 95% CI 0.47 to 1.22; P = 0.25), and heterogeneity was low (I² = 0.0%). Funnel plot inspection suggested possible asymmetry for blood loss and transfusion; however, Egger's test was not significant for blood loss (P = 0.842), whereas significant small-study effects were detected for transfusion (P = 0.002).

CONCLUSIONS

The current evidence indicates that TXA in primary TKA significantly reduces blood loss and transfusion requirements with no detected increase in DVT risk in the available randomized evidence. The blood loss analysis showed substantial heterogeneity, whereas the transfusion and DVT analyses were more consistent across studies.