Patients undergoing THA demonstrate a relatively high risk of requiring allogeneic blood transfusion. In the context of primary THA, several investigations regarding IV and topical TXA administration have reported the efficacy and safety of TXA in reducing blood loss and transfusions [13–16]. The combination of IV-TXA with topical TXA has been introduced and is used by surgeons in patients undergoing total knee arthroplasty (TKA) and THA with satisfactory results [17, 18, 21, 22]. Following preoperative IV-TXA administration, TXA is widely distributed across extracellular and intracellular compartments, rapidly reaching the maximum plasma concentration in 5–15 min. Furthermore, IV-TXA inhibits local fibrinolysis as soon as surgery is initiated, with maintenance of the plasma TXA concentration above the minimum therapeutic level for approximately 3 hours [23, 24]. However, concerns regarding the risk of DVT and PE due to systemic administration of high-dose TXA persist, hindering the widespread application of IV-TXA [25].
Compared with IV-TXA, topical TXA application has advantages such as ease of administration, inhibition of clot breakdown with maximum concentration at the bleeding site, and reduction in joint swelling, which leads to improved wound healing, with minimal systemic absorption [26, 27]. During surgery, most of the bleeding occurs during soft tissue release and acetabular and femoral canal preparation. Topical TXA administration directly targets the bleeding site in a surgical wound, maintaining maximum local TXA levels to induce partial microvascular hemostasis by preventing breakdown of the fibrin clot [28]. Considering the biological half-life of TXA in the bloodstream or joint space [29], topical TXA administration during wound closure can extend the effective time of TXA at the surgical site.
In the present study, the administration of 1 g topical TXA in combination with IV-TXA was more effective in reducing TBL, OBL, and HBL than the administration of IV-TXA alone. The post hoc power analysis revealed that the current study had > 80% power for comparing TBL, OBL, and HBL between the two groups. From immediately post-operation to 1-week post-operation, there was no significant change in Hb levels in the combined group compared with that in the IV only group. We speculate that this may be due to the differences in preoperative Hb levels, because the average Hb level in the IV only group was lower than that in the combined group (0.5 g/dL) preoperatively (combined group 12.9 ± 1.3 g/dL vs. IV only group 13.4 ± 1.4 g/dL; p = 0.086). However, the Hb drop was significant from immediately post-operation to POD 3, and the post hoc power analysis showed > 80% power, demonstrating no significant difference in Hb drop between POD 5 and 1-week post-operation. Therefore, TXA is effective in controlling the Hb drop from immediately post-operation to POD 3. In a randomized double-blind controlled trial, Yue et al. [16] compared the application of 3 g topical TXA with the application of a placebo, which revealed that the Hb drop was significantly lower in the topical group at POD 1 and POD 3. These findings are consistent with our results. Interestingly, in our study, although the Hb drop at POD 5 was not significantly different, it demonstrated a strong tendency toward significance (p = 0.051).
Notably, the TXA dose has not been standardized and remains controversial. TXA is frequently administered intravenously with a loading dose of 10 or 15 mg/kg, followed by continuous infusion or repeated bolus doses [30, 31]. Husted et al. randomized patients to receive TXA as a bolus IV injection of 10 mg/kg (maximum 1 g) for 10 min, approximately 15 min before incision. This resulted in reduced blood loss and a reduced need for blood transfusion. Furthermore, no patient reported prolonged drainage, infection, clinical DVT, or PE during hospitalization or at the last follow-up. For topical administration, the TXA dose ranged from 0.5 g TXA/100 mL normal saline to 3 g TXA/100 mL normal saline, as reported by Zhao et al. [32] in a meta-analysis of six randomized controlled trials. As mentioned earlier, Yue et al. [16], in a randomized double-blind controlled trial, administered 3 g TXA in 150 mL saline at three points during THA and reported that the topical application of 3 g of TXA significantly reduced bleeding and transfusions in patients undergoing primary THA without increasing the risk of DVT and PE. Several investigators have reported another strategy for the combined administration of TXA in the setting of THA; in most of these studies, the maximum dose of TXA was < 3 g [17, 18]. Xie et al. [17] performed a prospective randomized controlled trial and compared the results according to administration route: IV, topical, and a combination of the two. In all three groups, the TXA dose was < 3 g. They observed that patients undergoing primary unilateral THA in the combined group demonstrated an effective decrease in TBL, resulting in higher postoperative Hb levels without the risk of higher complication rates, compared to those in the other two groups. Yi et al. [18] performed a prospective randomized controlled trial and compared the results of placebo, IV-TXA, and the combination of IV-TXA and topical TXA. The TXA dose was < 3 g both in the IV-TXA and combined groups. TXA has been administered at different doses and using different routes in patients undergoing primary THA, with most investigators routinely administering TXA at a dose of no more than 3 g. They considered that a dose of < 3 g is safe and efficacious in these patients. In our study, in the combined group, 1 g of IV-TXA was combined with 1 g of topical TXA, and the total TXA dose in the two groups was < 3 g. In both groups, we observed no cases of DVT or PE during hospitalization and until the last follow-up.
The performance of drainage after THA remains controversial. The most important reasons for drainage include preventing the accumulation of hematomas and decreasing the risk of infection [33]. However, some studies have presented differing conclusions, stating that drainage increases blood loss, which may increase transfusion rates and provide an entry point for skin microorganisms, resulting in infections [34, 35]. Zhou et al. [36] performed a meta-analysis of 20 randomized controlled studies evaluating the use of closed-suction drains in patients undergoing THA. They reported a significant increase in the homologous transfusion rate in patients undergoing drainage, with no significant differences in the incidence of infections, hematomas, or thrombosis. Furthermore, they suggested that in patients undergoing elective THA, the routine use of closed-suction drains may result in more damage than benefits. Walmsley et al. [37] reported that the postoperative transfusion rate was significantly higher in the drainage group than in the no drainage group (33% vs. 26.4%, p = 0.042), concluding that drainage provides no clear advantage in the context of THA. Furthermore, a study by Valle et al. [38] showed that drainage confers no benefit in patients undergoing primary uncomplicated THA.
Most studies regarding TXA administration involved the use of drainage. We considered that a small amount of TXA may be lost owing to drainage, reducing the TXA concentration in the joint. A few studies have investigated primary THA without drainage [15]. However, no investigations have compared IV-TXA alone and IV-TXA combined with topical TXA in this population. In our study, to completely retain TXA in the joint, we did not perform any drainage; this approach was considered better for evaluating the effect of topical TXA. In the present study, only two patients needed transfusions, and in both groups, no patient presented with symptomatic hematoma, deep infection, or wound complications postoperatively, until discharge.
This study has several limitations. First, the study population was relatively small. We believe that a larger sample size is needed to effectively detect the difference in DVT and PE incidence between the two groups. Second, this study did not include a placebo group. IV-TXA may be significantly superior to a placebo but not as effective as the combination of IV-TXA and topical TXA. We considered that using combined administration as a control rather than a pure placebo was clinically a more useful and appropriate methodology.