The advantages of TXA administration in unilateral opening-wedge HTO (OW-HTO) have been proven in many retrospective studies and elaborate meta-analyses.19–23 Therefore, further reduction of the TBL, HBL, and drainage volume after SBDTT-HTO has been an important directive. The purpose of this study was to determine whether the sequential IV TXA regimen is effective and safe, from the perspective of reducing perioperative blood loss and drainage volume, with an additional detailed assessment.
The primary outcomes obtained in this study indicate that sequential IV TXA can effectively reduce TBL, HBL,drainage volume and maintain postoperative Hb values in patients. Compared with the TBL observed with a single-dose of TXA, two-dose reduced TBL by approximately 160 mL and multiple-dose reduced TBL by approximately 311 mL (1138 vs. 827 mL, p = 0.011). The calculation of HBL also confirmed the advantages of multiple doses of TXA. The mean HBL volumes in the multiple-dose, two-dose and single-dose groups were 416, 493, and 561 mL, respectively (p < 0.001). The changes in postoperative drainage volume among the three groups showed a similar trend to those in TBL and HBL. The drainage volume was reduced by approximately 124 and 172 mL in the two-dose and multiple-dose groups compared with that in the single-dose group. On POD#3, the Hb level in the multiple-dose group was higher than that in the two-dose and single-dose groups (p < 0.05), and the maximum Hb drop was also the lowest, indicating that multiple doses of TXA can reduce blood loss from POD#1 to POD#3. In particular, patients in multiple-dose had more advantages during the postoperative rehabilitation period, including early pain reduction and better QoL, without an increase in the incidence of postoperative vascular events, incision complications, and adverse reactions.
The effect of TXA administration on blood loss and subsequent complications after major orthopaedic surgery has been well described in previous studies. As a traditional anti-fibrinolytic drug, the effectiveness of TXA when administered intravenously, topically, or in combination has been proven. Aggarwal et al.24 found that topical administration of 15 mg/kg TXA in simultaneous bilateral TKA can effectively reduce TBL during the perioperative period, and the Western Ontario and McMaster Universities Arthritis Index score at 12 weeks and 6 months was better than that of the IV administration group. Kim et al.23 injected TXA intravenously at a dose of 10 mg/kg before and 6 h after tourniquet application and 24 h after surgery. The results demonstrated that the Hb level in the TXA group was higher than that in the control group on POD#1, POD#2, and POD#5 (p < 0.001). Moreover, the total drainage volume and TBL were lower in the TXA group than in the control group (p < 0.001). To the best of our knowledge, the pharmacokinetic study of IV TXA demonstrated that its half-life is approximately 3 h, and the therapeutic plasma concentration of TXA is 10 h from the time of administration;25 however, the hyper-fibrinolytic state of the body, which is caused by surgical trauma, reaches its peak at 6 h after surgery and continues until 18–24 h.26,27 The current trial had a shorter IV administration gap than that in the study mentioned above. Therefore, our study had a theoretical advantage in suppressing early postoperative fibrinolysis, thereby reducing postoperative blood loss and drainage volume. Our results confirm the superiority of the multiple-dose IV TXA treatment regimen to the two-dose and single-dose regimens. Some scholars reached an optimistic conclusion regarding the advantages of multi-dose IV TXA for TKA without tourniquet application26 and observed that the use of multiple-dose IV TXA did not increase blood loss during surgery.
Thus, good perioperative blood management can reduce blood loss and transfusion due to surgical trauma, reduce the incidence of anaemia, and maintain a high postoperative Hb level. It is also closely related to postoperative rehabilitation of physical function. Anti-fibrinolytic therapy, an important aspect of blood management that is considered to be closely related to the concept of enhanced recovery after surgery, has emerged as an area of particular research focus, and TXA has been apply this strategy in a clinical setting in our institution.28–31
The safety of TXA during the perioperative period of major orthopaedic surgery has been controversial. Hence, the pace of clinical promotion of TXA has been reduced.32 More safety concerns are associated with DVT and PE than with cerebral infarctions and gastrointestinal bleeding. Although some scholars reported that the incidence of DVT and PE in Asians is significantly lower than that in Europeans and Americans, the incidence is still higher following major surgery of lower extremity orthopaedics.33 Hence, this problem deserves attention. At present, most orthopaedic clinical trials are designed to test the haemostatic effect of TXA instead of its safety. For rare complications such as PE, the current clinical trial could not reach a definitive conclusion owing to the sample size. However, a large-scale retrospective study from China (including 1907 THA and 1505 TKA cases) concluded that TXA reduced blood transfusion rates without increasing the prevalence of DVT/PE.34 In this study, we used a combination of mechanical compression devices and chemical drugs to prevent thromboembolic events, and the results obtained were consistent with those of the above study. Therefore, we suggest that with reasonable intervention after SBDTT-HTO, the administration of multiple doses of IV TXA does not increase the risk of thrombotic events (p > 0.05).
In this study, there was one incision-site haematoma case in the single-dose and two-dose groups. In general, measures to avoid subcutaneous hematoma include appropriate soft tissue handling, meticulous haemostasis, wound closure without excess tension, and regular postoperative care. During the surgical procedure, the plate is placed in the subcutaneous plane and is covered only by a very thin layer of fascia and the skin; hematoma caused by exudation from the osteotomy site may endanger wound healing.22 In addition, a study showed that reducing the perioperative blood transfusion rate can reduce the incidence of wound complications.35 To our knowledge, although our study was the largest study on TXA administration in patients undergoing SBDTT-HTO, the sample size was still too small to detect differences in these rare complications. The incidence of adverse reactions of TXA, especially neurological symptoms, was higher in the multiple-dose group then single-dose and two-dose group. However, we could not determine whether this was because of adverse reactions after general anaesthesia or IV TXA. Notably, in the multiple-dose group, one patient developed rashes after being administered IV TXA; however, the symptoms improved after administration of dexamethasone.
Tzatzairis et al.26 observed that three doses of IV TXA in TKA can achieve higher knee function and QoL and significantly reduce pain in the early and late postoperative periods. Palanisamy et al.22 observed that after OW-HTO, the VAS score of the TXA group was lower than that of the control group on POD#2 but had no clinical significance because the difference was minor. Li et al.19 observed that the combined IV and local TXA protocol did not effectively improve knee HSS and VAS scores in patients after surgery (at 6 months postoperatively). A recent study has demonstrated that the use of a drainage tube did not increase blood loss when TXA was administered intravenously, and the VAS score and calf swelling in the early postoperative period were lower than those in the control group, effectively reducing the incidence of incision complications.8 Interestingly, the multiple-dose TXA regimen can effectively alleviate early postoperative pain in patients and can help patients exercise knee joint mobility as soon as possible. Early knee function recovery and pain improvement are favourable factors for predicting the QoL after HTO. This is the reason for the higher SF-12 PCS score in the three-dose group since the early postoperative period.
This study had certain limitations. First, the sample size of this study was small, and the study was conducted at a single centre. Prospective, large-scale, randomised, case–control studies are required to confirm these findings. Second, according to the perioperative rehabilitation guidelines for major orthopaedic surgery established by our institution, all patients received preventive anticoagulation after surgery, which might have had an impact on postoperative blood loss. Third, given the effectiveness and safety of TXA in previous studies, patients were not recruited to the control group. Fourth, some recent studies have highlighted surgery-associated factors that are associated with perioperative period blood loss during HTO, especially tourniquet application and navigation. Several studies have reported advantages associated with not using tourniquets in HTO, and the use of navigation to reduce blood loss. Here, we realized the advantages of navigation and the disadvantages of tourniquet application, and subsequent research will focus on performing navigation SBDTT-HTO without a tourniquet.