Intravenous administration of tranexamic acid to reduce blood loss during perioperative period in acetabular fracture surgery

studys have reported that topical use of TXA can reduce perioperative blood loss in acetabular fracture surgery. We aim to investigate the effect of intravenous administration of tranexamic acid (TXA) on perioperative blood loss during acetabular fracture surgery treatment groups were 51.5% (17/33), 23.0% (6/26), 19.2% (5/26), respectively. There was no statistically signicant difference in surgery-related blood transfusion rates between groups Intravenous administration of TXA in acetabular fracture surgery can reduce total blood loss, intraoperative blood loss, and postoperative hemoglobin drop without increasing the risk of venous thrombosis. Multiple administrations before surgery, and at 3 h and 6 h during surgery are more effective than single and repeated administration

Intravenous administration of tranexamic acid to reduce blood loss during perioperative period in acetabular fracture surgery ZhiDong

Introduction
As we all know, acetabular fractures are known as the crown surgery of trauma orthopedics. Most acetabular fractures are caused by high-energy injuries [1]. Due to the complex anatomical structure and abundant venous plexus around the acetabulum, fracture surgery is di cult, requiring anatomical reduction, strong internal xation, and early functional exercise [2]. During the operation, there is a lot of bleeding, which often requires blood transfusion. This increases the clinical blood pressure and the risks associated with blood transfusions, such as fever, allergies, infections, hemolysis, etc [3].
Tranexamic acid (TXA) is a synthetic plasmin inhibitor that acts to stop brin by blocking the lysine-binding site of plasminogen molecules and acting against brinolysis [3]. Several studies have reported that perioperative intravenous infusion of TXA can reduce total blood loss, intraoperative blood loss, and blood transfusion rate during joint replacement surgery, and that it does not increase the risk of venous thrombosis. Its safety has been recognized by clinical experts [4][5][6][7]. fracture surgery. However, there have been no reports on the clinical application of TXA in the treatment of acetabular fractures. The purpose of this study was to determine whether intravenous administration of TXA can reduce total blood loss and intraoperative blood loss, whether it safe to use TXA multiple times, and whether it increases deep vein thrombosis.

Inclusion and exclusion criteria
Inclusion criteria: The inclusion criteria were as follows: 1. Preoperative HB, PLT, PT, and APTT were normal; 2. Preoperative imaging (X-ray and CT) suggested a diagnosis of acetabular fracture.

Surgical Methods And Perioperative Management
The three groups of operations were completed by the same group of trauma directors, all of which used the lateral rectus abdominis approach, K-L approach, and anterior-posterior approach. In the single treatment group, 22 cases were treated with lateral rectus abdominis, 9 cases with K-L approach, and 2 case was combined with anterior-posterior approach; in the repeated treatment groups 18 cases with lateral rectus abdominis approach, 6 cases with K-L approach, and 2 cases was combined anterior-posterior combined approach; In the multiple treatment group, 19 cases were treated with lateral rectus abdominis approach, 5 cases with K-L approach, and 2 cases with anterior-posterior combined approach. The fracture types were divided into two categories according to the Letournel-Judet classi cation. Simple fractures (anterior wall, anterior column, posterior wall, posterior column, and transverse type) and complex fractures (posterior wall with posterior wall column, transverse type with posterior wall, double column, T-type, and anterior with posterior half-horizontal type). Simple and complex fractures in a single treatment group, repeated treatment group, multiple treatment group were found in 18 and 15, 14 and 12, and 13 and 13 cases, respectively. There were no signi cant differences in fracture types among groups (χ2 = 0.133, P = 0.936). All patients underwent general anesthesia, during which an anesthesiologist controlled their blood pressure to maintain it at 90/60 mmHg.
A drainage tube was routinely placed in the three groups of patients, and the drainage was recorded. The drainage tube was generally removed 24 h after surgery. No patient showed bleeding after surgery, and on the next day. According to the guidelines for the prevention of venous thromboembolism in major orthopedic surgery in China, low molecular heparin was combined with physical methods for anticoagulation. In cases where there was more drainage after surgery, the hemoglobin level progressively decreased; the hemoglobin level should be stabilized in such cases before anticoagulation. Ultrasound examination of both lower extremities was performed ve days after surgery to con rm whether there was thrombosis. If there was swelling of the lower extremities accompanied by pain and to determine whether there is thrombosis, ultrasound examinations of both lower extremities were required to be performed. Pulmonary embolism was judged based on clinical manifestations.
The patient decided whether to sit up depending on the type of fracture and the degree of xation stability during the operation. The lower extremities could perform quadriceps functional exercise and sputum pump exercise on the second day. Postoperative ultrasound could exclude thrombus formation and the extremities could be treated with lower extremity air pump.
Surgery-related blood transfusion rate: blood transfusion index: Hb < 70 g/L or Hb ≥ 70 g/L, the patient develops dizziness, paleness, weakness, and other discomfort. During the operation, depending on the bleeding of the patient, it is up to the anesthesiologist and the clinician to decide whether blood transfusion is needed. Three categories of surgery-related blood transfusion rates were recorded. The blood transfusion rate in each category was calculated as number of patients requiring intraoperative blood transfusion + number of patients requiring postoperative transfusion / total number of patients.

Statistical analysis
Statistical analysis was performed using SPSS 23.0 (SPSS, USA) statistical software. The data are expressed as one-way analysis of variance for the normal distribution and Tukey method for comparison between groups. Categorical variables were analyzed via chi-square test or Fisher's exact test. P < 0.05 was considered statistically signi cant.

Total and intraoperative blood loss
Total blood loss during the operation was calculated by Gross and Nadler equation [9,10] in the three groups. Total blood loss in the single treatment group, repeated treatment group and the multiple treatment group was 932.7 ± 181.8 ml, 843.4 ± 153.0 ml, and 748.0 ± 145.2 ml, respectively. Intraoperative blood loss in these three groups was 624.2 ± 138.7 ml, 567.3 ± 144.1 ml, and 521.1 ± 98.1 ml, respectively. The values of total blood loss and intraoperative blood loss were lower in the repeated administration group and the multiple administration group than in the single administration group. Further, total blood loss and intraoperative blood loss values were lower in the multiple administration group than in the repeated administration group. The differences were statistically signi cant (P < 0.05) (Fig. 1).

Drainage and hemoglobin decline
The drainage rates in the single administration group, repeated administration group, and multiple administration group were 100.1 ± 30.1 ml, 86.1 ± 42.2 ml, and 64.2 ± 29.0 ml, respectively. The decline in hemoglobin level on the rst day after operation was 32.2 ± 5.3 g/l, 27.6 ± 3.8 g/l, 24.4 ± 4.4 g/l in the three groups, respectively. The drainage rates and decline in hemoglobin level in the single treatment group were higher than those in the repeated treatment group and multiple treatment group; further, the values in the multiple dose group were higher than those in the repeated treatment group. There were statistically signi cant differences between groups (P < 0.05).

Preoperative blood transfusion rate and surgery-related transfusion rate
The damage mechanism is divided into high-energy damage (e.g., car accident and high-altitude fall injury) and low-energy damage (e.g., walking fall and falling at home) [11]. All patients in the three groups mainly showed high-energy injuries, and the damage mechanism was signi cantly different between groups (P > 0.05). Acetabular fractures were serious and resulted in a lot of bleeding. The preoperative blood transfusion rate was 75.7% (25/33) in the single treatment group and 69.2% (18/26) in the repeated treatment group. The preoperative blood transfusion rate in the multiple treatment group was 65.3% (17/26). There was no signi cant difference in the preoperative blood transfusion rate among the three groups (P > 0.05). The single treatment group showed a surgery-related blood transfusion rate of 51.5% (17/33), and the repeated treatment group showed a surgery-related blood transfusion rate of 23.0% (6/26). Further, the multiple treatment group showed a surgeryrelated blood transfusion rate of 19.2% (5/26). There was no signi cant difference in the transfusion rate among the three groups (χ 2 = 8.512, P = 0.014).
incidence of thrombotic events There were 6, 4, and 5 cases of intramuscular venous thrombosis in the single treatment group, repeated treatment group, and the multiple treatment group, respectively. There was no statistical difference among the three groups. No symptoms of deep venous thrombosis and pulmonary embolism were found in all three groups (Table 2). Two patients in the single treatment group showed an incision redness and exudate, which healed after dressing change. One patient in the repeated treatment group had postoperative subcutaneous hematoma, which healed after drainage, No patient in the multiple treatment groups had incisions problem, and there was no statistical difference among the three groups in terms of incision complications.

Discussion
At present, a large number of studies report that TXA is safe and effective in hip and knee joint replacement, regardless of the mode of administration, intravenous, topical, or combination [12][13][14][15]. However, no study has reported on the intravenous infusion of TXA in the acetabulum in terms of its effect on blood loss during the perioperative period in these fractures. In this study, patients with acetabular fractures were treated with single, repeated, or multiple intravenous infusions. It was concluded that intravenous TXA administration can reduce total perioperative blood loss, intraoperative blood loss, and postoperative thrombotic events. There was a decrease in hemoglobin and a surgically relevant blood transfusion rate in all groups and the differences among the single treatment, repeated treatment, and multiple treatment groups were statistically signi cant. However, there was no statistically signi cant difference in the incidence of postoperative thrombotic events and incision complications among groups. Therefore, we conclude that intravenous infusion of TXA is safe and effective in reducing perioperative blood loss during acetabular fracture surgeries, and multiple doses of TXA are more effective than a single dose and repeated dose.
The effectiveness of intravenous use of TXA TXA is a synthetic lysine analog that inhibits brinolytic activity by competitively inhibiting the binding of plasminogen to brin, thereby inhibiting brinolysis and reducing perioperative blood loss. Chen et al [12] conducted a meta-analysis using TXA in TKA and THA, and concluded that intravenous use of TXA can reduce perioperative blood loss, which is worthy of clinical recommendation. A multicenter retrospective study on simultaneous bilateral knee replacement surgery reported that intravenous use of TXA is safe and effective, and reduces perioperative blood loss without increasing complications [16].
Andersson et al [8] found that the half-life of aminocycline is approximately 3 h. Accordingly, in this study, we repeated the treatment, and the second and third intravenous infusions of TXA in the multiple treatment group were administered at intervals of 3 h, which can further reduce intraoperative and postoperative bleeding. It has been reported in the literature that the use of TXA in THA can reduce perioperative blood loss and hemoglobin loss in patients, and repeated application of TXA can further reduce perioperative blood loss and hemoglobin loss [17]. In the repeated treatment group and the multiple treatment group, TXA was administered again 3 h later and 3 h and 6 h later, respectively, and total blood loss, intraoperative blood loss, and postoperative hemoglobin drop were reduced. The conclusions reached are consistent with the abovementioned literature.

Safety of intravenous use of TXA
Although the literature reports that intravenous use of TXA can reduce perioperative blood loss during THA and TKA and reduce the clinical blood transfusion rate, whether TXA acts as an anti brinolytic drug and whether TXA increases the incidence of thrombosis remain unknown and are important clinical questions that every clinician should consider. Husted et al [18] reported preoperative 10 mg/kg, followed by 1 mg/kg/h of continuous intravenous infusion of TXA for 10 h, and no increase in postoperative thrombosis-related events was observed. Another study reported [19] that intravenous infusion of aminocycline in total knee arthroplasty can reduce blood loss, but does not increase deep vein thrombosis and pulmonary embolism. Hines et al [20] reported that intravenous aminocycline can reduce the transfusion rate in total hip revision and does not increase the rate of deep vein thrombosis. In our study, patients in all three groups underwent double-limb arteriovenous color Doppler ultrasonography, and no deep vein thrombosis was observed in the three groups. There was no signi cant difference in the incidence of intramuscular venous thrombosis among the three groups. The conclusions are similar to those reported in the literature, suggesting that single and repeated intravenous TXA administration is safe and does not increase the incidence of thrombosis.

Advantages and disadvantages of this study
This study concluded that intravenous administration of TXA during acetabular fracture surgery can reduce the total amount of blood loss and intraoperative blood loss, and does not increase the incidence of thrombotic events. The conclusions reported in this study are more objective. First, the choice of patients undergoing acetabular fracture surgery who were included in the study had a strict case inclusion and exclusion criteria, which reduces the selection bias; Second, total perioperative blood loss was calculated by the Gross equation and the Nadler equation. The results were accurate and reliable.
Third, the three groups of operations were completed by the same clinicians, which reduced the bias. However, there were some limitations of the current study. First, the sample size of the three groups of patients was small, less than 30 cases, and larger samples randomized controlled study are required to draw a conclusion. Second, all postoperative venous thrombosis were evaluated with lower extremity venous ultrasound instead of lower extremity venography. Third, this study is retrospective study, the level of argument is not high. Thus, a large-sample prospective randomized study is required to be conducted in the future.

Conclusions
In summary, for patients with acetabular fractures, intravenous infusion of TXA can reduce total blood loss, intraoperative blood loss, and postoperative hemoglobin decline rate, and does not increase the risk of thrombosis. Availability of data and materials The datasets generated and/or analysed during the current study are not publicly available due to continuing research using this data, but are available from the corresponding author on reasonable request.

Ethics approval and consent to participate
The study was approved by the Ethics Committee of the First A liated Hospital of Soochow University, and all selected patients signed informed consent forms.

Consent for publication
Not applicable.

Con ict of interests
The authors declare that they have no con ict of interests. Figure 1 Total and intraoperative blood loss