Less Blood Loss With Tranexamic Acid in Primary Total Hip Arthroplasty Using the Direct Anterior Approach: a One-center Retrospective Observational Study

Background: It is still not known whether tranexamic acid is benecial for the minimally invasive surgical approach to total hip arthroplasty (THA). This study seeks to investigate the ecacy and safety of intravenous tranexamic acid (TXA) in primary THA via the direct anterior approach (DAA). Methods: We performed a retrospective analysis of prospectively collected data on 70 patients with non-traumatic avascular necrosis of the femoral head who underwent total hip arthroplasty (THA) via the DAA between October 2017 and October 2018. Patients were divided into two groups: TXA group (39 patients who did receive 1.5g TXA intravenously) and control group (31 patients who did not receive TXA). Patients were assessed by the operative time, postoperative hemoglobin (HB) drop, transfusion rate, postoperative length of hospital stays (LHS), deep vein thrombosis (DVT), and Harris hip score (HHS). Results: The total blood loss, hidden blood loss, and postoperative HB drop in the TXA group were signicantly lower than those in the control group (p < 0.05). There was no statistical difference in terms of intraoperative blood loss, operation time, transfusion rate, postoperative LHS, HHS, and the incidence of DVT between the two groups (p > 0.05). Conclusion: TXA may be reduce perioperative blood loss and not increase complications, in THA via the DAA.


Introduction
Total hip arthroplasty (THA) has been widely used for the treatment of end-stage hip disease, and it can effectively relieve pain, restore function and improve the quality of life [1]. It has been reported that the total blood loss can be as high as 2000 mL, and the transfusion rate was as high as 37% during perioperative period of THA [2][3][4]. Massive blood transfusion not only increases the risk of surgery, but also causes the spread of viral diseases, hemolytic reactions, immunologic reactions and other transfusion-related risks [5,6].
With the popularization of minimally invasive concept and the continuous improvement of prosthesis materials and design, there are a variety of THA surgical approaches available clinically, such as direct anterior approach (DAA), anterolateral approach, posterior approach, posterolateral approach, SuperPATH approach, lateral approach. Among them, the DAA is a minimally invasive surgical approach through the intermuscular space and nerve gap. This approach has the advantages of minimizing soft tissue disruption and reducing the incidence of dislocation [7][8][9]. As a synthetic anti brinolytic agent, TXA has been shown to be effective in reducing blood loss and transfusion rate in THA [10,11]. However, few studies have explored the e cacy of TXA on perioperative blood loss in primary THA using the DAA [12,13] -in other words, it is still not known whether tranexamic acid is bene cial for the minimally invasive surgical approach to THA. Therefore, this study aimed to investigate the e cacy and safety of intravenous TXA in THA via the DAA.

Patients
We performed a retrospective analysis of prospectively collected data on 70 patients (70 hips) with nontraumatic avascular necrosis of the femoral head who underwent total hip arthroplasty (THA) via the direct anterior approach (DAA) between October 2017 and October 2018. Patients were divided into two groups: TXA group (39 patients who did receive 1.5g TXA intravenously) and control group (31 patients who did not receive TXA). The Medical Ethics Committee of the A liated Hospital of Xuzhou Medical University approved the study protocol according to the declaration of Helsinki and all study participants gave their written informed consent.

Study setting
All surgeries were performed by the senior author (Z.G.C) using cementless THA via DAA. All patients received a general anesthetic and received a same design of the femoral stem (CLS stem; Zimmer, Warsaw, USA) and cup (Trilogy; Zimmer, Warsaw, USA). We did not use a wound drain following surgery.
In the TXA group, TXA was given as a 1.5 g intravenous infusion 10 minutes prior to incision; the control group did not receive TXA.
All Patients were managed with a similar perioperative regimen, including intravenous prophylactic antibiotics, prophylaxis against venous thrombosis and post-operative pain control.
Patients were transfused if postoperative hemoglobin level was less than 70g/L or when the hemoglobin of a patient was more than 70 g/L and less than 100 g/L but with a bad mental status, palpitation or pallor. All patients underwent deep vein ultrasound of the lower limbs 1 week postoperatively to detect thrombosis.
The total red blood cell volume loss = PBV × (Hctpre − Hctpost), Hctpre = the initial preoperative Hct level, Hctpost = the Hct of the third postoperative day.
The total blood loss = 1000×the total red blood cell volume loss/ (the average of the Hctpre and Hctpost).
The postoperative HB drop = HBpre − HBpost, HBpre = the initial preoperative HB level, HBpost = the HB of the third postoperative day.
The obvious blood loss = Intraoperative blood loss + postoperative blood loss.
The hidden blood loss = the total blood loss-obvious blood loss.

Statistical methods
All the statistical analyses were performed using SPSS version 19.0 (SPSS Inc. USA). Means are presented as mean ± SD, Student-t test was used to analyze the normal distributed numerical variable; Pearson chi-square test or Fisher exact test was used to analyze the qualitative variable. The signi cance level used for all tests was p < 0 .05.

Patient characteristics
All patients were followed for three months. Detailed distribution of patient demographics and characteristics was shown in Table 1.

Operative variable
The operative time, intraoperative blood loss, hidden blood loss, total blood loss, preoperative HB level, HB level of the rst postoperative day, HB level of the third postoperative day, postoperative HB drop, and transfusion rate was shown in Table 2. In the TXA group, 2.6% (1/39) required blood transfusion with 2unit (400mL) red blood cells suspension (RBCs), whereas in the control group, 12.9% (4/31) required blood transfusion with 8-unit (1600 mL) RBCs (2 units per patient). The total blood loss, hidden blood loss, and postoperative HB drop in the TXA group were signi cantly lower than those in the control group (p < 0.05). There was no statistical difference in terms of the operative time, intraoperative blood loss, and transfusion rate between the two groups (p > 0.05).

Clinical results and complications
All patients were successfully completed the operation. All patients did not receive blood transfusion on the third postoperative day. There was no statistical difference in terms of postoperative LHS, HHS, and the incidence of DVT between the two groups (p > 0.05) ( Table 2).
Two patients (1 patient per group) sustained intraoperative fractures of the calcar during seating of the stem, and the fractures were treated by cerclage wire xation. Subsidence of the stem during loading was not observed after three months of follow-up. There were two patients (1 patient per group) with asymptomatic DVT who did not receive any special treatment. No incision infection occurred in the two groups. No patient died during the study period.

Discussion
TXA is a synthetic derivative of the amino acid lysine, which can reduce brinolysis through the reversible blockade of lysine binding sites on plasminogen molecules [16]. More and more evidences show that TXA can effectively reduce perioperative blood loss and transfusion rate in THA. Most studies have been performed on the posterolateral approach [11,17] or the lateral approach [18] or the posterior approach [19,20] in THA. However, there is less research on TXA in the DAA for THA [12,13]. This study aimed to explore whether TXA reduced perioperative blood loss and the rate of blood transfusion in patients undergoing THA via the DAA.
In the present study, the intravenous infusion of 1.5 g of TXA which was effective in reducing total blood loss, hidden blood loss, and the degree of Hb drop, but did not signi cantly intraoperative blood loss and transfusion rate during perioperative period in DAA THA. Fraval et al. [12] performed a single-center randomized, double-blind trial in which 101 patients underwent THA via DAA, and 50 of them received TXA during the perioperative period. It was found that TXA could signi cantly reduce the blood loss (including intraoperative blood loss and calculated blood loss), but there was no statistical signi cance in transfusion rate between the both groups. Our results are consistent with Fraval et al. [12], except for the intraoperative blood loss. We speculate that the reason is that these patients in our study have a younger age, lower of BMI and shorter of operative time than those in Fraval et al. [12] study. In addition, our results are not exactly the same as Free et al. [13] study, they found that the transfusion rate after TXA was 1.2% in THA using DAA, which was signi cantly lower than the transfusion rate of 11.1% in the control group. We speculate that the reason is that these patients in our study have a younger age, lower of BMI and lower of ASA score than those in Free et al. [13] study. Whether TXA can reduce the transfusion rate for THA via DAA requires more sample size and more prospective studies to determine.
Several studies [12,23] have found that the use of TXA can reduce the LHS during the perioperative period of THA. However, our study found that the use of TXA during perioperative period of THA via DAA did not shorten the postoperative LHS. We speculate that the reason is that DAA is a minimally invasive procedure that can shorten the LHS. Whether TXA can reduce the LHS for THA via DAA requires more sample size and more prospective studies to determine.
Many literatures [11,24,25] have reported that the use of TXA did not increase the incidence of DVT in patients undergoing THA. However, Nishihara et al. [26] conducted a study to observe whether TXA increased the risk of DVT in lower limbs without routine chemical thromboprophylaxis, and nally found that the use of TXA would increase in the incidence of distal DVTs in the muscular veins. Our study found that 1 case of DVT occurred in the TXA group, and 1 case in the control group, the difference was not statistically signi cant (p = 1.000). Perioperative use of TXA during THA via DAA did not increase the incidence DVT in the lower extremities.
In this study, there are several limitations. The incidence of DVT in the lower extremities was assessed only in the short term. Our sample size is small and the results may be biased. A larger randomized prospective trial is required to further improve the relevant experiments to determine the e cacy and safety of TXA in the perioperative period of THA via DAA.

Conclusion
Single administration of 1.5 g intravenous infusion 10 minutes prior to incision, may be effectively reduce the perioperative blood loss in primary THA through DAA, and may be not increase the incidence of DVT of lower extremities.