Total knee arthroplasty (TKA) is the ideal surgical option for treating severe pain in the arthritic knee [1]. According to the literature, approximately 20% of patients with surgical indications have preoperative anaemia and,therefore, are at a relatively higher risk of requiring blood transfusion [2, 3]. Intraoperative homeostatic control is important and can avoid possible procedural and transfusion complications in patients with anaemia in the postoperative period [2, 4]. It is known that blood component administration increases the risk of infections and immune reactions [4, 5]. Several haemostatic control strategies have proven effective in recent years [6, 7]. Classical strategies for the control of intraoperative bleeding include the use of a pneumatic tourniquet, anaesthesia and low-pressure haemostasis [4, 8]. Recently, tranexamic acid (TXA) has been used as an adjuvant to such measures [6 - 18]. TXA is an analogue of lysine and inhibits fibrinolysis and blocks, with high affinity, the lysine to plasminogen binding sites, thereby preventing formation of the complex between plasminogen, fibrin and tissue plasminogen activator . Orthopaedics initially hesitated to use this substance, as there was a lack of information regarding the safety of TXA use in relation to thromboembolic events [7, 11,]. However, more recent studies have demonstrated the benefits of TXA in TKA, revealing different administration routes and therapeutic dosages [5 - 7, 9, 10]. It is known that persistent bleeding during the postoperative period may cause local complications, such as haematoma, seroma and consequently greater pain and reduced function postoperatively . Therefore, the hypothesis of this study was that, in addition to reducing bleeding, the topical application of TXA at the end of surgery before closure of the joint capsule and surgical incision would be effective in reducing drain output.

This study carried out in a single centre GBH general hospital associated with American international institute of medical science, Udaipur. minimum six month follow up was taken for each patient. All surgery carried out by single surgeon. All patients with end-stage knee osteoarthritis (K-L grade 4) awaiting surgery were eligible for the study. We excluded patients with a history of cardiovascular problem , a history of thromboembolic disease, bleeding disorder, known allergy to tranexamic acid. The subjects were divided into 2 groups : those using TXA and a control group (no applied substance). Allocation was randomized by the surgeon, and the subjects were monitored for 6 months. The groups were named “Control” (100 patients undergoing total knee prosthesis without application TXA) and TXA (100 patients undergoing total knee prosthesis and topical application of TXA during the TKA procedure). The dose chosen for topical treatment followed the existing literature data on the use of TXA in total knee prosthesis and was 1.0 g (4 x 5 ml ampoules with a concentration of 50 mg/ml) . Patients were not told to which group they belonged and were completely unaware of this information until the end of the project. Preoperative data included age at the time of the operation, gender, and preoperative hemoglobin level. There were no differences between groups regarding the preoperative data (Table 1). Hemoglobin levels were measured preoperatively and 6 hours, 24 hours, 48 hours, and 5 days postoperatively The lowest value of the postoperative hemoglobin level obtained until the 5th postoperative day was used to calculate the hemoglobin drop. Transfusions were performed in compliance with our hospital policy. Blood transfusions were planned for asymptomatic patients with a hemoglobin level of <9.0 gm%.

Table 1. Demographic data of patients Variables Control group (n=100) TA Group (n=100) p-value Age (yr), mean (range) 67.2 (53-86) 69.4 (52-84) 0.051 Sex (M:F) 42:58 38:62 0.073 Hb (gm%) mean±SD 11.6±1.8 11.4±1.6 0.069 BMI (Kg/m2) (Avg) 25.8 24.9 0.762 SD: standard deviation. The surgical technique was medial parapatellar approach with epidural anesthesia. A posterior-stabilized type implant was used and the patella was not resurfaced in all cases. application of TXA all over the exposed joint using a syringe and maintained for 5 minutes. After this period, the joint capsule and incision were closed with drain without negative suction . The drains were emptied every day and the amount of drained blood was measured.drain removal done if its less than 100 ml in last 24 hr. On average, drains were kept for 3 days (range, 2 to 5 days). All patients received as prophylaxis for deep venous thrombosis a dose of 40 mg of enoxaparin 12, 24 and 48 hours after surgery and were prescribed 10 mg Rivaroxaban daily for 10 days at home. Antibiotic prophylaxis was achieved with 2 g intravenous cefazolin during anaesthetic induction and 1 g of cefazolin every 8 hours for 48 hours. The dressing was changed in the hospital on the 2nd postoperative day. Patients used a walker for 21 days with a full load from the 2nd postoperative day. Physical therapy was also initiated on admission and was maintained until the second month, postoperatively, 3 times a week with a physical therapy protocol focusing on analgesia, gain in flexion and walking training. Radiological knee examinations were performed in the immediate post-operative period and upon return to the clinic 2 months later. The total volume of drained blood and the decrease in hemoglobin at 6 hours, 24 hours, 48 hours and 5 days postoperatively were recorded. Blood transfusions were recorded as the number of units of packed erythrocytes. Statistical significance of differences in the mean values of continuous variables such as age, preoperative hemoglobin, total volume of drained blood. Table 2. Postoperative Hemoglobin, Drain Output, and Blood Transfusion Variables Control group (n=100) TA group (n=100) p-value Drained blood (ml) 645 ± 270.4 470± 210.7 0.003 No. of patient receiving blood transfusion (%) 54 (54%) 39 (39%) 0.013 Mean unit of transfusion (unit) 1.38 1.03 0.005 Hb gm/dl postop 6hr 24hr 48hr 5 days 11.2±1.7 10.8±1.4 9.7±1.9 10.2±1.3 11.3±1.9 11.0±1.6 10.8±1.3 10.9±2.2 0.712 0.031 0.003 0.001 Hb drop ( preop to 5 th postop day) 2.6±0.9 1.9±0.7 0.003 Values are presented as mean±standard deviation. The mean postoperative total volume of drained blood was lower in the tranexamic acid group (470±210.7 mL) than in the control group (645.0±270.4 mL) (p=0.003). There was a reduction in the transfusion rate in the tranexamic acid group compared with the control group (39% vs. 60%; p=0.013). The mean units of transfusion were smaller (p=0.005) in the tranexamic acid group than in the control group (1.03 units vs. 1.38 units). The hemoglobin level at 6 hours postoperatively was almost similar (p=0.712) in the two groups, but it was greater in the tranexamic acid group than in the control group at 24 hours, 48 hours, and 5 days postoperatively at statistically significant levels (Table 2). The hemoglobin drop was calculated as the difference between the lowest postoperative hemoglobin level and the preoperative hemoglobin level. This drop was significantly high for the control group (2.6 gm/L) compared to the tranexamic acid group (1.9 gm/dL) (p=0.003). The total amount of blood loss calculated using the hemoglobin balance method was significantly less in the tranexamic acid group than in the control group (p=0.002) (Table 2). There were no cases of symptomatic DVT or pulmonary embolism (PE) in both groups during the 3 months of follow-up. Table 3 shows the amount of evident blood loss on each postoperative day measured based on the drain output and the number of patients still utilizing the drain. Postoperative day 1 losses were significantly different between the groups, but no difference was found on subsequent days. Table 3. Postoperative Drain Output variables Control group TA group p-value POD1 410±190.3 (100) 286±184 (100) 0.006 POD2 140±80 (78) 124±63.4 (73) 0.389 POD3 114±60.6 (52) 112±58.6(38) 0.712 POD4 98±38.2(23) 69±23.8(12) 0.051 Values are presented as mean±standard deviation (number). POD: postoperative day. a)p-values are for unpaired two-tailed Student t-test.

The topical administration of 1 g of TXA was effective in reducing bleeding based on the haemoglobin level. This fact, demonstrated again in this study, was already known [16]. In published studies, the most common administration route for the application of TXA in TKA has been intravenous. Intravenous administration in a single dose or repeated doses was used initially in orthopaedic procedures, based on previous studies in cardiac surgery . However, there is evidence demonstrating that only a fraction of the injected drug reaches the target tissue, which in turn reduces its effectiveness [10]; that up to 95% of the drug can be eliminated in the urine; and that in patients with impaired kidney function, the dosage needs to be corrected . When administered in high doses or injected quickly, minor gastrointestinal symptoms, such as nausea and vomiting, have been reported . Intraarticular use generates cost savings because lower doses can be used without systemic side effects. Most of reports have evaluated blood losses in drains at 24–48 hours after surgery. Similar to these results, we also observed a reduction of 40% in blood loss on postoperative day 1 . The difference in drain output between two groups was observed particularly on 1st postoperative day. after which it has no effect on postoperative bleeding. Therefore, postoperative bleeding after 1st postoperative day showed no significant difference between two groups. Despite this, the overall blood loss in the tranexamic acid group was 35% less than that in the control group. This was because most bleeding after arthroplasty tends to occur during the first 24 hours. In addition, not only was the number of patients requiring transfusions less, the total number of transfusions required for each patient was significantly less in the tranexamic acid group compared to the control group. In this study, the postoperative hemoglobin was between 8–10 gm% at the time of transfusion in most of the patients who were transfused (17 in tranexamic acid group and 19 in control group) due to tachycardia not responding to fluid management. Tranexamic acid creates a prothrombotic state by inhibiting fibrinolysis. This raises the concern of DVT. The safety of tranexamic acid has been well established in literature. Recent reviews and metaanalyses have found no increased risk of thromboembolic events. We recognize limitations to our study. First, the sample size (200 patients) was small to address some questions. Second, the study design was not double-blinded and can only be regarded as a prospective comparative trial. Third, the female to male ratio was high because most TKA patients in study are females. Female patients may have lower preoperative hemoglobin levels and greater blood transfusion rates after TKA than males; however, the ratios of females to males and the preoperative hemoglobin levels were not different between the two groups in the study.

In addition to reducing bleeding, topical tranexamic acid could be effective in reducing total blood loss and the need for blood transfusion after TKA for patients without any complication of thromboembolic disease. Ethical Approval: Approved Acknowledgement: None Source of funding: None Conflict of Interest :No potential conflict of interest reported.

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