Allogenic blood transfusions after TKA carried significant potential risks, which should be avoided as well as possible, so TXA should be applied. IV application of TXA has been confirmed as effectively decreasing postoperative blood loss and transfusion rate in TKA patients[19, 20]. However, there is no clear consensus on the optimal regimen of IV application of TXA. Administering one pre-operative dose and one subsequent post-operative dose is one of the most common IV application practices. The interval of doses is usually three hours, which is because TXA has a plasma half-life of three hours. This is the first meta-analysis to identify the efficacy and safety of a single preoperative dose and an additional dose of IV TXA in TKA.
This study showed that IV TXA twice could reduce postoperative blood loss than the placebo group and IV TXA once group, which was consistent with those of previous studies[7, 21]. There is a difference existing between single dose and multiple doses, and two doses of TXA may be the optimal regimen for blood loss. IV TXA twice had a higher postoperative blood loss as compared with the IV TXA once and topical/oral group, which may due to the total TXA dose. The efficacy of TXA was positively correlated with total dose, and the use of TXA at two intervals could maintain the exposure level of tranexamic acid to systemic circulation in order to achieve a better effect of reducing postoperative bleeding after TKA.
In three RCTs included, IV TXA twice with subsequent TXA was more effective than IV TXA twice group. Wang et al compared IV 20mg/kg TXA twice with IV 20mg/kg TXA twice and subsequent long-term oral TXA for 14 days, finding the latter produced less blood loss and less swelling and ecchymosis without increasing the risk of complications. Takuya et al compared IV 1g TXA twice with IV 1g TXA twice and intra-articular (IA) 1g TXA, showing IV and IA TXA regimen significantly reduced perioperative blood loss compared with only IV TXA. Lee et al compared IV 10mg/kg TXA twice with IV 10mg/kg TXA twice and IA 1g TXA, concluding that combined IA TXA administration further reduces blood loss after TKA in comparison to IV use alone. IV TXA twice with subsequent TXA, either oral or IA, and either long or short term, bleeding could be better controlled.
In addition, IV TXA twice had a similar efficacy with topical TXA in terms of reducing postoperative blood loss. One study indicated that topical 1g TXA and IV 10 mg/kg TXA once have similar safety and efficacy for reducing perioperative blood loss in TKA. Gomez-Barrena et al concluded that a single topical dose of 3g of TXA was not inferior to two 15mg/kg IV TXA doses. We thought IV TXA twice and topical TXA achieved equal control of blood loss. TXA applied locally before wound closure targeted the bleeding, which could reduce the significant increase in local fibrinolysis associated with tourniquet release.
IV TXA twice had significantly lower transfusion rate as compared to the placebo group. No significant differences in were observed between IV TXA twice and TXA control group in terms of transfusion rate. No significant differences in were observed in terms of DVT incidence. When the patients determined to apply TXA during the perioperative period, IV TXA twice could be used without without safety concerns. Egger’s test indicated that there was no significant publication bias for postoperative blood loss, transfusion rate, and DVT incidence. Therefore, the results of this study were relatively stable.
The authors acknowledge that the current study has several limitations. Firstly, the sample of IV TXA twice in this study was small. Secondly, we only pooled DVT complication. Finally, there may be high quality non-English studies that could have influenced the outcomes of our meta-analysis, but were excluded due to the selection criteria. A longer follow-up period is required to compare the safety profile and functional outcome differences.