==== Front BMC Musculoskelet Disord BMC Musculoskelet Disord BMC Musculoskeletal Disorders 1471-2474 BioMed Central London 6627 10.1186/s12891-023-06627-z Research Efficacy and safety of using aminocaproic acid and tranexamic acid during the perioperative period for treating trochanteric fractures in elderly femurs Yusufu Alimujiang 12 Haibier Abuduwupuer 12 Ren Zheng 12 Qin Qi 12 Zhang Ziyi 12 Zhou Yuan 12 Ran Jian 850253752@qq.com 12 1 grid.460730.6 Department of Orthopedics of Trauma, Sixth Affiliated Hospital of Xinjiang Medical University, Orthopaedic Hospital of Xinjiang Uygur Autonomous Region, No.39 Wuxing Road, Urumqi, People’s Republic of China 2 grid.13394.3c 0000 0004 1799 3993 Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region People’s Republic of China 3 7 2023 3 7 2023 2023 24 54627 4 2023 12 6 2023 © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/ Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Background Tranexamic acid (TXA) has long been the antifibrinolytic hemostatic drug of choice for orthopedic surgery. In recent years, the hemostatic effect of epsilon aminocaproic acid (EACA) has gradually been recognized by orthopedic surgeons and has begun to be used in hip and knee arthroplasty with little mention of the comparison of these two drugs; Therefore, this study compared the efficacy and safety of EACA and TXA in the perioperative period of elderly patients with trochanteric fractures to verify whether EAC could be a "qualified alternative" to TXA and to provide theoretical support for the clinical application of TXA. Methods Two hundred and forty-three patients who received proximal femoral nail antirotation (PFNA) for trochanteric fractures from January 2021 to March 2022 at our institution were included and divided into the EACA group (n = 146) and the TXA group. (n = 97) determined by the drugs used in the perioperative period The main observations were blood loss and blood transfusion.The second second outcome was blood routine, coagulation, Hospital complications and complications after discharge. Results The perioperative EACA patients had significantly lower significant blood loss (DBL) than the TXA group (p < 0.0001) and statistically significant lower C-reactive protein in the EACA group than in the TXA group on postoperative day 1 (p = 0.022). Patients on perioperative TXA had better postoperative day one (p = 0.002) and postoperative day five erythrocyte width than the EACA group (p = 0.004). However, there was no statistically significant difference between the two groups in the remaining indicators in both drugs: blood items, coagulation indicators, blood loss, blood transfusion, length of hospital(LOH), total hospital expense, and postoperative complications (p > 0.05). Conclusion The hemostatic effects and safety of EACA and TXA in the perioperative application of trochanteric fractures in the elderly are essentially similar, and EACA can be considered for use as an alternative to TXA, increasing the flexibility of physicians to use it in the clinical setting. However, the limited sample size included necessitated a high-quality, large sample of clinical studies and long-term follow-up. Keywords Proximal femoral fracture Tranexamic acid Aminohexanic acid Blood loss issue-copyright-statement© BioMed Central Ltd., part of Springer Nature 2023 ==== Body pmcBackground Proximal femoral fractures are one of the most common types of hip fractures in the elderly population [1]. Due to chronic underlying diseases such as osteoporosis in the elderly, proximal femoral fractures have a high mortality rate and are therefore also referred to as the "last fracture of life". In elderly patients, due to their poor physical condition and complex and variable disease, early surgery can restore the muscle strength of the lower limbs through early functional exercise, which can lead to a rapid recovery and reduce the probability of complications [2, 3]. Intramedullary fixation surgery has become the treatment of choice for intertrochanteric femoral fractures [4]. Although PFNA has the advantages of a short operative time and minimal medically induced trauma, intraoperative marrow expansion can lead to increased occult blood loss, and it is estimated that patients with femoral intertrochanteric fractures have an average perioperative blood loss of up to 2100 m [5], and the occurrence of anemia is more common. Studies have reported perioperative transfusion requirements for intertrochanteric femur fractures to range from 30% to 84.6%, depending on the type of fracture and age [5–8]. Blood transfusions are associated with many adverse events, including hemolytic transfusion reactions, postoperative infections, longer hospital stays, and costly treatment [9]. Therefore, there is an urgent need to establish an optimal strategy to reduce blood loss to reduce the cost of surgery and improve patient prognosis. A variety of hematoprotective measures have been used clinically, including spinal anesthesia, tourniquets, and reinfusion drainage, but each of these methods has different limitations [10]. However, the use of antifibrinolytics has been shown to be a more effective perioperative hematologic management measure than previous strategies [11]. TXA and EACA are the most common antifibrinolytic agents with essentially similar antifibrinolytic mechanisms [12]. Previous studies have shown [13] that both antifibrinolytic agents are associated with a significant reduction in perioperative blood loss and transfusion requirements in orthopedic surgery. To date, very few studies have reported the efficacy of aminocaproic acid for perioperative use in intertrochanteric fractures of the femur. Therefore, we conducted a retrospective cohort study to investigate the efficacy of EACA versus TXA in terms of hemostatic effect and safety of PFNA in elderly intertrochanteric fractures to investigate whether EACA can be used as an alternative to TXA in such fractures, and to draw clinical conclusions and to promote it. Methods Patients and design This is a retrospective study approved by the Ethics Committee of the Sixth Affiliated Hospital of Xinjiang Medical University, ethical approval number LFYLLSC20221018-01. All of the study subjects signed the informed consent form (Fig. 1).Fig.1 Patient flow chart According to the recommendations in the literature [14], all TXA groups in our trial were given the standard dose of 1 g TXA i.v. TXA is at least 7 times higher than EACA on a molar basis and therefore requires less drug dose; second, several studies have shown that the optimal dose of EACA is 15 to 30 min before the incision and an additional dose (2 to 4 g) before incision. The drug dose was in accordance with the recommendations of the anesthesia team of the Sixth Affiliated Hospital of Xinjiang Medical University. Inclusion criteria: ① Diagnosis of intertrochanteric fracture by imaging examination (X-ray/CT). The presentation of a pertrochanteric femoral fracture of types 31-A1 to A3 according to the AO classification was defined as the primary inclusion criterion (Fig. 2). ②Age ≥ 70 years old ③No hematologic disorders ④Normal preoperative vascular ultrasound findings in both lower extremities ⑤Normal coagulation function and no long-term anticoagulant ⑥Complete medical records ⑦Patients who behaved autonomously and gave informed consent for the test.Fig. 2 (A) pre-operative x-ray film of right femoral intertrochanteric fracture; (B) x-ray film after PFNA operation of right femoral intertrochanteric fracture Surgical procedure and postoperative rehabilitation After admission, the affected limb underwent continuous tibial tubercle bone traction and a routine preoperative examination. Patients with internal diseases underwent special internal examinations. In addition, anemia, electrolyte disorder, hypoproteinemia and diabetes were actively corrected before surgery. The repositioning is performed on a traction bed using epidural or general anesthesia and confirmed by fluoroscopy with a C-arm. A straight incision was made 5 cm at the tip of the great trochanter of the femur, and the hole at the tip of the large tuber was opened to expand the pulp and insert the guide needle. The main nail was placed after fluoroscopic confirmation by C-arm and the femoral neck screw and hip screw guide needle were monitored by the C-arm X-wire machine. The proximal anti-rotation screw was drilled first, then the distal compression screw was screwed, and finally the distal 2 interlocking screws were screwed, and the incision was closed layer by layer. All patients were routinely given a 5% glucose injection (500 mL:25 mg, Sichuan Kelun Pharmaceutical Co., Ltd.) + sodium lactate Ringer injection (500 mL, Xinjiang Huashidan Pharmaceutical Co., Ltd.) toreplenish blood volume and maintain electrolyte balance within 4 h after the operation. The antithrombotic regimen was the same in both groups: all patients were given 4,100 IU of calcium nadroparin injection (0.4 mL:4100 IU, Nanjing Jianyou Biochemical Pharmaceutical Co., Ltd.) within 6 h after the operation, and 4100 IU nadroparin calcium was injected subcutaneously every 24 h until the patients were discharged from the hospital 2 weeks after surgery. If the patients experienced pain and discomfort, ibuprofen codeine extended-release tablets or intramuscular diazoxide were given. All patients were encouraged to perform equal length and knee flexion exercises of the ankle and quadriceps on the second day after the operation. On postoperative days 1, 3, 5, and 9, the competent physician cleans and changes the incision with iodophor and observes the recovery of the incision. Any abnormalities should be reported and treated promptly. Ultrasound examination of blood vessels of both lower extremities was performed on the 7th day after the operation, and stitches were routinely removed On postoperative day 12, but if the patient developed complications such as incision edge necrosis or fat liquefaction, the competent physician should report to the superior physician, and the stitches could not be removed and discharged until the incision healed completely. After discharge, the patient should be informed to come to the hospital for regular review of lower limb vascular ultrasound and coagulation function 1 or 2 months after surgery; during this period, the patient should be strictly bedridden and should not bear weight on the floor. Outcome measurements Demographic characteristics and medical history of the patients were documented preoperatively. The primary outcomes were blood loss and blood transfusion volume. The indicators of blood loss included total blood loss (TBL), dominant blood loss (DBL) and hidden blood loss (HBL). TBL = 1000 × total erythroid loss/average hematocrit. DBL = Intraoperative blood loss + postoperative drainage flow (all patients had no drain placed postoperatively). HBL = TBL-DBL + blood transfusion. Patient’s blood volume(PBV) [15] = K1 × (height 3) + K2 × (weight) + K3), male patients K1 = 0.3669, K2 = 0.03219 and K3 = 0.6041, while female patients K1 = 0.3561, K2 = 0.03308 and K3 = 0.1833 [16, 17]. Total red blood cell loss = PBV × (preoperative hematocrit-postoperative hematocrit). Mean hematocrit = (preoperative hematocrit + postoperative hematocrit)/2. No postoperative drains were placed in all patients, so the drainage rate was 0. According to the bleeding amount in the suction storage tank and the gauze blood suction tank of the nurse under the operating table, there may be errors, but it is meaningful for the surgeon to quickly determine the amount of bleeding. Secondary outcomes included routine blood tests, C-reactive protein and coagulation function, LOH, operative time, total hospital expense, complete weight-bearing time and postoperative complications (thromboembolic adverse events, fatal events, and recurrent fractures). LOH was calculated from the first day of admission to the day of discharge. Total hospitalization expenses were based on the amount spent by the patient between admission and discharge. Statistical analysis SPSS26.0 software was used to analyze the data. The results of all measured data in this study were expressed as mean ± standard deviation, and the classified data were expressed as percentags and frequencies. Because no significant deviation from normality was detected, t-tests were used to compare continuous variables between the two treatment groups (EACA and TXA), and chi-square tests or Fisher exact tests were used to compare categorical variables. Results Patient demographics A total of 243 patients with trochanteric fractures (97 in TXA and 146 in EACA) were collected for this study. Baseline characteristics in both groups were comparable, as summarized in Table 1.Table 1 Baseline characteristics Index EACA(n = 146) TXA(n = 97) t P Age(y, y,X¯±S 76.55 ± 5.06 77.17 ± 5.48 0.380 0.369 Sex (n, Male/Female) 50/96 36/61 0.209 0.647 BMI kgm2,X¯±S 23.36 ± 3.84 23.76 ± 4.03 0.787 0.432 Position(Left/Right) 67/79 46/51 0.055 0.815  Basic disease(n)  Hypertension 74 42 1.274 0.259  Diabetes 45 25 0.724 0.395  Cardiovascular system 57 36 0.092 0.762  Nervous system 37 22 0.225 0.636  Respiratory system 14 8 0.127 0.721  Osteoporosis 27 12 1.621 0.203 Preoperative values  Red blood cell(1012/L) 3.83 ± 0.65 3.95 ± 0.71 1.321 0.188  Platelets(1012/L) 209.96 ± 76.51 214.54 ± 84.96 0.437 0.662  Red blood cell width(SD) 41.93 ± 10.53 41.87 ± 9.60 -0.051 0.960  Hemoglobin(g/L) 116.94 ± 20.44 121.35 ± 20.73 1.636 0.103  Hematocrit(%) 35.29 ± 6.56 36.35 ± 5.99 1.275 0.204  C-reactive protein 37.49 ± 43.20 34.22 ± 41.34 -0.588 0.557  Total protein (g/L) 64.83 ± 7.49 65.00 ± 71.11 0.171 0.864  Albumin(g/L) 38.93 ± 5.36 42.83 ± 33.53 1.383 0.168  Serum ferritin(umol/L) 8.75 ± 7.78 8.83 ± 5.20 0.090 0.929  D-dimer (mg/L) 8.18 ± 10.03 9.17 ± 11.02 0.726 0.469  PT activity(%) 104.36 ± 16.31 106.48 ± 17.97 0.950 0.343  INR 1.06 ± 0.12 1.03 ± 0.14 -1.717 0.087  Fibrinogen 3.84 ± 1.17 3.64 ± 1.22 -1.319 0.189  Fibrin degradation product 37.05 ± 38.52 39.02 ± 42.91 0.373 0.710 The continuous value was given as the mean and the standard deviation. Categorical values are given as the number of patients. TXA Tranexamic acid, EACA Epsilon aminocaproic acid, BMI Body mass index = weight/height2, INR International normalized ratio Blood loss and blood transfusion volume DBL (164.31 ± 123.98 ml) in the EACA group was significantly lower than that in the TXA group (261.49 ± 190.44 ml) (p < 0.0001); PBV, TBL, HBL, and perioperative transfusion were also significantly different between the two groups (p > 0.05). The related outcomes are summarized in Table 2.Table 2 Comparison of blood loss and blood transfusion volume Index EACA(n = 146) TXA(n = 97) t p PBV(L) 3.86 ± 0.71 4.01 ± 0.72 1.493 0.137 TBL(ml) 580.92 ± 863.65 746.30 ± 731.14 1.552 0.122 DBL(ml) 164.31 ± 123.98 261.49 ± 190.44 4.819  < 0.0001* HBL(ml) 625.51 ± 793.47 711.61 ± 750.05 0.847 0.398 Volume of transfusion(ml) 234.25 ± 362.94 223.08 ± 317.59 0.005 0.847 Transfusion (n, 100%) 41(28.1%) 37(38.1%) 2.707 0.100 The continuous value was given as the mean and the standard deviation. Categorical values are given as the number of patients. PBV Patient’s blood volume. TBL Total blood loss, DBL Dominant blood loss, HBL Hidden blood loss *The p＜0.05，and The differences between the two groups were statistically significant Index of routine blood tests, C-reactive protein and coagulation function on the first and fifth days after surgery The C-reactive protein level (68.53 ± 40.80) was significantly better than that in the TXA group (82.55 ± 49.69) (p = 0.022); the red cell width (39.24 ± 15.08 and 35.56.94 ± 16.91) was significantly better than that in the aminohexanic acid group (43.41 ± 11.52, 42.46 ± 12.48) (p < 0.05). However, there were no significant differences in red blood cells, platelets, red blood cell width, hemoglobin, hematocrit, total protein, albumin, serum iron ion, D-dimer, PT activity, international standard ratio, fibrinogen, and fibrin degradation products on days 1 and 5 after surgery (p > 0.05). The related outcomes are summarized in Table 3. LOH, operation time, hospital expense, complete weight-bearing time and operation time.Table 3 Comparison of the results of routine blood, C-reactive protein and coagulation tests on day 1 after surgery Varible EACA(n = 146) TXA(n = 97) t p RBC(1012/L) 3.27 ± 0.50 3.26 ± 0.58 -0.201 0.841 Platelets(1012/L) 261.97 ± 85.16 259.70 ± 90.45 -0.199 0.843 Red blood cell width 43.41 ± 11.52 39.24 ± 15.08 -2.435 0.022 HB 100.19 ± 15.47 100.25 ± 16.52 0.031 0.975 Hematocrit 35.29 ± 6.56 36.35 ± 5.99 -0.642 0.522 C-reactive protein 68.53 ± 40.80 82.55 ± 49.69 2.402 0.022* Total protein 64.83 ± 7.49 65.00 ± 7.11 0.941 0.348 Albumin 32.48 ± 4.03 32.78 ± 4.32 0.548 0.584 Serum ferritin 4.97 ± 2.81 5.39 ± 4.68 0.878 0.381 D-dimer (mg/L) 6.31 ± 5.01 5.20 ± 4.67 -1.735 0.084 PT activity 94.91 ± 12.66 94.68 ± 16.45 -0.126 0.905 INR 1.11 ± 0.14 1.10 ± 0.17 -0.742 0.459 Fibrinogen 4.56 ± 1.09 4.77 ± 1.25 1.352 0.178 FDP 24.17 ± 20.66 21.11 ± 23.55 -1.068 0.286 The continuous value was given as the mean and the standard deviation. RBC Red blood cell, HB Hemoglobin, INR international normalized ratio, FDP Fibrin degradation product *The p＜0.05，and The differences between the two groups were statistically significant There was no significant difference in the length of hospital stay, surgery time, total hospitalization cost or complete weight-bearing time between the two groups (p > 0.05). Related outcomes are summarized in Tables 3 and 4. The comparison of red blood cells and hemoglobin before and after surgery is shown in Figs. 3 and 4.Table 4 Comparison of the results of routine blood, C-reactive protein and coagulation tests on day 5 after surgery Varible EACA(n = 146) TXA(n = 97) t p RBC(1012/L) 3.24 ± 0.50 3.23 ± 0.53 -0.097 0.923 Platelets(1012/L) 295.91 ± 92.52 300.23 ± 112.80 0.324 0.746 Red blood cell width 42.46 ± 12.48 36.54 ± 16.91 -3.13 0.004 HB 97.52 ± 13.48 100.52 ± 18.83 1.446 0.178 Hematocrit 30.63 ± 4.48 30.24 ± 4.81 0.388 0.699 C-reactive protein 64.35 ± 43.59 76.32 ± 52.76 1.918 0.056 Total protein 56.20 ± 7.06 57.05 ± 6.72 -0.435 0.664 Albumin 33.30 ± 6.25 33.41 ± 3.85 0.153 0.878 Serum ferritin 6.48 ± 3.84 6.61 ± 3.52 0.277 0.782 D-dimer (mg/L) 5.10 ± 2.66 4.65 ± 2.65 -1.277 0.203 PT activity 98.10 ± 12.98 96.61 ± 16.51 -0.786 0.433 INR 1.11 ± 0.14 1.15 ± 0.63 0.676 0.499 Fibrinogen 4.93 ± 1.15 5.15 ± 1.31 1.345 0.180 FDP 20.43 ± 13.97 18.62 ± 14.24 -0.978 0.329 The continuous value was given as the mean and the standard deviation. RBC Red blood cell, HB Hemoglobin, INR International normalized ratio, FDP Fibrin degradation product Fig. 3 Comparison of the first, postoperative day and fifth postoperative day after RBC surgery Fig. 4 Comparison of the first, postoperative day and fifth postoperative day after HB surgery LOH, operation time, hospital expense, complete weight-bearing time and operation time There was no significant difference in the length of hospital stay, surgery time, total hospitalization cost or complete weight-bearing time between the two groups (p > 0.05). The related outcomes are summarized in Table 5.Table 5 Comparison of length of stay, operative time, total hospital expense, and complete weight bearing time Varible EACA(n = 146) TXA(n = 97) t p LOH(day) 18.35 ± 5.73 18.91 ± 9.24 0.584 0.560 Operative time (min) 85.61 ± 37.14 85.00 ± 31.86 -0.134 0.894 Expenses∆ 44,300.39 ± 13,486.93 43,320.27 ± 16,970.33 -0.500 0.618 Full weight bearing time(day) 73.14 ± 17.98 76.25 ± 16.09 1.378 0.170 The continuous value was given as the mean and the standard deviation. LOH: length of hospital stay Stay. ∆ Results are presented in Chinese yuan Complications There was no significant difference in thromboembolism, mortality, or recurrent fracture between the two groups. Fifty-nine cases of muscular calf vein thrombosis (MCVT) occurred in 59 patients in the EACA group and 37 patients in the TXA group. DVT occurred in 20 patients in the EACA group and 117 patients in the TXA group. There was PE in the EACA group and 1 case in the TXA group. In addition, one person in the EACA and TXA groups died in the hospital. The number of deaths at 12-month postoperative follow-up was 10 in the EACA group and 6 in the TXA group. Five people in the EACA group had fractures again within 12 months and seven in the TXA group.The related outcomes are summarized in Table 6.Table 6 Complications Varible EACA(n = 146) TXA(n = 97) t p Thromboembolic event(n, 100%)  MCVT 59 (40.41) 38 (39.17) 0.037 0.847  DVT 20 (13.69) 11 (11.34) 0.981 0.612  PE 0 (0.00) 1 (1.03) 2.170 0.338 mortality(n, 100%)  Intrahospital mortality 1 (0.68) 1 (1.03) 2.170 0.338  Mortality in 12 months after surgery 10 (6.84) 6 (6.18) 0.042 0.838  Internal fixation failure/secondary fractur 5 (3.42) 7 (7.21) 1.785 0.182 MCVT Muscular calf vein thrombosis, DVT Deep venous thrombosis, PE Pulmonary embolism Discussion Elderly patients are characterized by advanced age, many basic diseases, poor compensatory ability of organs and organs, high incidence of complications, low self-care ability, and high difficulty of nursing. In addition, most elderly patients had anemia. Although most intertrochanteric fractures can be treated by minimally invasive surgery, reducing perioperative blood loss is the key to treatment due to massive bleeding. The use of TXA in hip and knee replacement surgery is well established, whereas the use of EACA in intertrochanteric fractures of the femur has rarely been reported, so we performed this study. TXA can reduce blood loss and transfusion by reversibly blocking fibrinolysis. Since the first application of TXA in total knee arthroplasty in 1995, numerous practices and studies have confirmed that it is effective in reducing perioperative blood loss and transfusion rates in hip and knee arthroplasty without increasing the incidence of deep vein thrombosis lower extremity [18]. TXA has been widely used in orthopedic surgery [19, 20]. EACA can inhibit the activator of plasminogen so that plasminogen cannot be converted into plasmin and then inhibit the dissolution of protein. It is suitable for the prevention and treatment of bleeding caused by hyperfibrinolysis. Earlier it was widely used in cardiac surgery and only recently in elective orthopedic hip and knee arthroplasty [21]. Although the efficacy and safety of EACA have been clinically proven [22], there are fewer studies on TXA. This study is a retrospective cohort study comparing the hemostatic effect and safety of the above two drugs in elderly patients with femoral intertrochanteric fracture during the perioperative period, n the hope of providing a theoretical basis for clinical decisions on drug use. The hemostatic effects of two drugs: TXA and EACA, are two drugs commonly used in clinical orthopedic surgery. Previous studies have shown that the mechanisms of action of these two drugs are similar, but few studies have conducted a comprehensive and direct comparison of the two drugs [23, 24]. The results of this study showed that the width of erythrocytes in the tranexamic acid group was significantly better than that in the aminocaproic acid group on postoperative days 1 and 5, with statistically significant differences (p < 0.05) WEI et al. [25] conducted a retrospective study showing that tranexamic acid can effectively and safely reduce postoperative blood loss and blood transfusion rates in elderly patients with intertrochanteric fractures. TIAN et al. [26] concluded that tranexamic acid can significantly reduce recessive blood loss in intramedullary fracture surgery in elderly patients. Recently, Churchill et al. [27] reported that EACA and TXA have similar clinical efficacy in reducing blood loss and transfusion requirements during hip replacement, which seems to be more economically advantageous over TXA; therefore, their team suggested a replacement for tranexamic acid in orthopedic surgery. This is consistent with the findings of the authors. The use of aminocaproic acid in the treatment of intertrochanteric fractures of the femur has been reported less frequently. Zhang et al. [28] reported that aminocaproic acid can significantly reduce perioperative blood loss and blood transfusion rates in elderly patients with intertrochanteric fractures treated with PFNA. EACA has been widely used in perioperative hip and knee arthroplasty. Hobbs et al. [29] reported that EACA can reduce blood loss and the blood transfusion rate during primary joint replacement. A randomized controlled trial of 194 patients undergoing total knee arthroplasty showed that the estimated blood loss was higher in the EACA group than in the TXA group when EACA was given intravenously at the start of tourniquet inflation and before the initial incision [30]. This is not entirely consistent with our results. Our results showed that the dominant blood loss in the EACA group (164.31 ± 123.98) was significantly lower than that in the TXA group (261.49 ± 190.44), and the difference was statistically significant (p < 0.0001). There was no significant difference in total blood loss, recessive blood loss or perioperative blood transfusion between the two groups (p > 0.05). Combining the above literature and the results of this trial, it can be seen that the hemostatic effects of EACA and TXA are similar. Safety of the two drugs: Thromboembolism is a serious complication that can lead to death after major orthopedic surgery, of which pulmonary embolism and deep venous thrombosis of the lower extremities account for the largest proportion [31]. In general, antifibrinolytic drugs inhibit fibrinolysis by blocking the lysine binding site of plasminogen and therefore increase the potential risk of perioperative thrombosis in surgical patients. However, the safety of EACA and TXA has recently been reported to be very reliable [21, 28] and does not increase the incidence of thromboembolism while stopping bleeding [22]. A study and meta-analysis did not clearly show that the antifibrinolytic drugs TXA or EACA increased the risk of thrombosis [32–34], and the incidence of complications such as surgical site infection, hematoma, deep venous thrombosis and pulmonary embolism was similar between the two drugs. In a report on the safety of EACA and TXA, the overall incidence of pulmonary thromboembolism in these two drugs was 0.15% and 0.19%, respectively, with no significant difference between the two groups [35]. DONG et al. [36] evaluated six studies (756 participants) of aminocaproic acid in total hip arthroplasty and total knee arthroplasty and reported that aminocaproic acid did not increase the risk of thromboembolic events during the perioperative period of joint replacement. Data from the randomized controlled study by YANG et al. showed no significant difference in the length of stay between the amino EACA and TXA groups (P > 0.05). In terms of safety, 3 patients in the EACA group and 2 patients in the TXA group experienced MCVT complications, but the difference between the two groups was not statistically significant (P > 0.05), and none of them had acute thrombotic complications such as DVT or PE [30]. The results of this study showed no significant difference in the incidence of thromboembolic events between EACA and TXA in perioperative patients with intertrochanteric fractures, and there was no significant difference in long-term effects (complete weight-bearing time, follow-up mortality within 12 months and the incidence of internal fixation failure or secondary fracture). These studies are consistent with the results of our trial, indicating no significant difference between the two drugs in terms of risk of complications such as thromboembolism. Limitations of the study ① This trial was a retrospective cohort study, and all data were collected from the database of our hospital. There was some selection bias and recall bias, which may have affected the results. Multicenter, randomized controlled clinical trials should be conducted in the future, and the sample size should be expanded. ② The optimal doses of EACA and TXA have not been determined, so the dose of the drug used in this trial may produce inaccurate results. Conclusions The perioperative efficacy and safety of EACA and TXA in elderly patients with trochanteric fractures were generally similar. EACA can be considered a substitute for TXA, which increases the flexibility of clinical medication. However, the sample size included was limited, so it is necessary to conduct high-quality, large-sample long-term follow-up clinical studies. Abbreviations EACA Epsilon-aminocaproic acid TXA Tranexamic acid; proximal femoral nail antirotation (PFNA) BMI Body mass index RBC Red Blood Cell HB Hemoglobin HCT Hematocrit INR International normalized ratio FDP Fibrin degradation product PBV Patient’s blood volume TBL Total blood loss DBL Dominant blood loss HBL Hidden blood loss LOH Length of hospital stay MCVT Muscular calf vein thrombosis DVT Deep venous thrombosis PE Pulmonary embolism Acknowledgements Not applicable. Authors’ contributions Study design, conception, and critical revision: Alimujiang Yusufu and Jian Ran. Analysis and interpretation of data: Abuduwupuer Haibier and Zheng Ren. Literature search and drafting of manuscript: Alimujiang Yusufu, Ziyi Zhang and Yuan Zhou. Alimujiang Yusufu and Qi Qin contributed to critical revision of the manuscript for important intellectual content and approved the final version of the manuscript. All authors read and approved the final version of the manuscript. Funding Not applicable. Availability of data and materials Follow-up regarding the perioperative use of hemostatic agents for intertrochanteric fractures in older femoral patients is not complete, so the dataset analyzed in this study is not publicly available but is available to the corresponding author on reasonable request. Declarations Ethics approval and consent to participate We confirm that all experiments were performed in accordance with the Declaration of Helsinki. The study was approved by the Ethical Committee of the Sixth Affiliated Hospital of Xinjiang Medical University, NO. LFYLLSC20221018-01. Each patient provided written informed consent before participating in the study. Consent for publication Not applicable. Competing interests Not applicable. Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Alimujiang Yusufu and Abuduwupuer Haibier contributed equally to this work, as co-first author. ==== Refs References 1. Kragh AM Waldén M Apelqvist A Bleeding and first-year mortality following hip fracture surgery and preoperative use of low-dose acetylsalicylic acid: an observational cohort study BMC Musculoskelet Disord 2011 12 254 10.1186/1471-2474-12-254 22059476 2. Morrell AT Layon DR Scott MJ Enhanced Recovery After Primary Total Hip and Knee Arthroplasty: A Systematic Review J Bone Joint Surg Am 2021 103 20 1938 1947 10.2106/JBJS.20.02169 34166275 3. de Vincentis A Behr AU Bellelli G Management of hip fracture in the older people: rationale and design of the Italian consensus on the orthogeriatric co-management Aging Clin Exp Res 2020 32 7 1393 1399 10.1007/s40520-020-01574-4 32358728 4. Hasegawa I Hasegawa M Livingstone JP What's New in Geriatric Acetabular Fractures Hawaii J Health Soc Welf 2022 81 3 Suppl 1 19 24 35340934 5. Tengberg PT Foss NB Palm H Tranexamic acid reduces blood loss in patients with extracapsular fractures of the hip: results of a randomised controlled trial Bone Joint J 2016 98-b 6 747 53 10.1302/0301-620X.98B6.36645 27235515 6. Vochteloo AJ Borger van der Burg BL Mertens B Outcome in hip fracture patients related to anemia at admission and allogeneic blood transfusion: an analysis of 1262 surgically treated patients BMC Musculoskelet Disord 2011 12 262 10.1186/1471-2474-12-262 22104041 7. Mohib Y Rashid RH Ali M Does tranexamic acid reduce blood transfusion following surgery for inter-trochanteric fracture? A randomized control trial J Pak Med Assoc 2015 65 11 Suppl 3 S17 20 26878513 8. Haghighi M Ettehad H Mardani-Kivi M Does tranexamic acid reduce bleeding during femoral fracture operation? Arch Bone Jt Surg 2017 5 2 103 108 28497100 9. Chen AF Klatt BA Yazer MH Blood utilization after primary total joint arthroplasty in a large hospital network Hss J 2013 9 2 123 128 10.1007/s11420-013-9327-y 24009534 10. Tobias JD Strategies for minimizing blood loss in orthopedic surgery Semin Hematol 2004 41 1 Suppl 1 145 156 10.1053/j.seminhematol.2003.11.025 14872436 11. Xie H Yang YS Tian SM Tranexamic versus aminocaproic acids in patients with total hip arthroplasty: a retrospective study BMC Musculoskelet Disord 2022 23 1 999 10.1186/s12891-022-05922-5 36401231 12. Gharaibeh A Savage HI Scherer RW Medical interventions for traumatic hyphema Cochrane Database Syst Rev 2019 1 1 Cd005431 30640411 13. Culliford D Maskell J Judge A Future projections of total hip and knee arthroplasty in the UK: results from the UK Clinical Practice Research Datalink Osteoarthr Cartil 2015 23 4 594 600 10.1016/j.joca.2014.12.022 14. Lee C Freeman R Edmondson M The efficacy of tranexamic acid in hip hemiarthroplasty surgery: an observational cohort study Injury 2015 46 10 1978 1982 10.1016/j.injury.2015.06.039 26190627 15. Nadler SB Hidalgo JH Bloch T Prediction of blood volume in normal human adults Surgery 1962 51 2 224 232 21936146 16. Gao FQ Li ZJ Zhang K Four methods for calculating blood-loss after total knee arthroplasty Chin Med J (Engl) 2015 128 21 2856 2860 10.4103/0366-6999.168041 26521781 17. Gross JB Estimating allowable blood loss: corrected for dilution Anesthesiology 1983 58 3 277 280 10.1097/00000542-198303000-00016 6829965 18. Porter SB White LJ Osagiede O Tranexamic Acid Administration Is Not Associated With an Increase in Complications in High-Risk Patients Undergoing Primary Total Knee or Total Hip Arthroplasty: A Retrospective Case-Control Study of 38,220 Patients J Arthroplasty 2020 35 1 45 51.e3 10.1016/j.arth.2019.08.015 31522854 19. Wu J Zhou YQ Deng JH Ideal intraarticular application dose of tranexamic acid in primary total knee arthroplasty: a prospective, randomized and controlled study Ann Transl Med 2020 8 21 1353 10.21037/atm-20-3064 33313098 20. Tsukada S Kurosaka K Nishino M Intraoperative intravenous and intra-articular plus postoperative intravenous Tranexamic acid in total knee arthroplasty: a placebo-controlled randomized controlled trial J Bone Joint Surg Am 2020 102 8 687 692 10.2106/JBJS.19.01083 32053522 21. Bravo D Josephson AM Bradaschia-Correa V Temporary inhibition of the plasminogen activator inhibits periosteal chondrogenesis and promotes periosteal osteogenesis during appendicular bone fracture healing Bone 2018 112 97 106 10.1016/j.bone.2018.04.016 29680264 22. Harley BJ Beaupré LA Jones CA The effect of epsilon aminocaproic acid on blood loss in patients who undergo primary total hip replacement: a pilot study Can J Surg 2002 45 3 185 90 12067170 23. Li G Sun TW Luo G Efficacy of antifibrinolytic agents on surgical bleeding and transfusion requirements in spine surgery: a meta-analysis Eur Spine J 2017 26 1 140 154 10.1007/s00586-016-4792-x 27671279 24. Lu X Lin J Low molecular weight heparin versus other anti-thrombotic agents for prevention of venous thromboembolic events after total hip or total knee replacement surgery: a systematic review and meta-analysis BMC Musculoskelet Disord 2018 19 1 322 10.1186/s12891-018-2215-3 30193575 25. Wei H Xiao Q He J Effect and safety of topical application of tranexamic acid to reduce perioperative blood loss in elderly patients with intertrochanteric fracture undergoing PFNA [J] Medicine (Baltimore) 2021 100 34 e27123 10.1097/MD.0000000000027123 34449517 26. Tian S Shen Z Liu Y The effect of tranexamic acid on hidden bleeding in older intertrochanteric fracture patients treated with PFNA Injury 2018 49 3 680 684 10.1016/j.injury.2018.01.026 29426608 27. Churchill JL Puca KE Meyer ES Comparison of ε-Aminocaproic Acid and Tranexamic Acid in Reducing Postoperative Transfusions in Total Hip Arthroplasty J Arthroplasty 2016 31 12 2795 9.e1 10.1016/j.arth.2016.05.011 27286909 28. Zhang R Yang Z Lei T Effects of aminocaproic acid on perioperative hidden blood loss in elderly patients with femoral intertrochanteric fracture treated with proximal femoral nail anti-rotation J Int Med Res 2019 47 10 5010 5018 10.1177/0300060519872037 31526169 29. Hobbs JC Welsby IJ Green CL Epsilon Aminocaproic acid to reduce blood loss and transfusion after total hip and total knee arthroplasty J Arthroplasty 2018 33 1 55 60 10.1016/j.arth.2017.08.020 28939033 30. Peng Y Jun Ma Junfeng Z Randomized controlled study of aminohexanoic acid and tranexamic acid for total hip replacement Chin J Orthop Surg 2022 30 3 214 218 31. Shuai F Tianlong W Perioperative anemia and new progress in patient blood management Int J Anesthesiol Resuscitation 2022 43 5 514 517 32. Liu Q Geng P Shi L Tranexamic acid versus aminocaproic acid for blood management after total knee and total hip arthroplasty: a systematic review and meta-analysis Int J Surg 2018 54 Pt A 105 112 10.1016/j.ijsu.2018.04.042 29723672 33. Yang ZG Chen WP Wu LD Effectiveness and safety of tranexamic acid in reducing blood loss in total knee arthroplasty: a meta-analysis J Bone Joint Surg Am 2012 94 13 1153 1159 10.2106/JBJS.K.00873 22623147 34. Liu Y Meng F Yang G Comparison of intra-articular versus intravenous application of tranexamic acid in total knee arthroplasty: a meta-analysis of randomized controlled trials Arch Med Sci 2017 13 3 533 540 10.5114/aoms.2017.67278 28507566 35. Lu C, Guo H, Hao Y, et al. A prospective randomized controlled study of tranexamic acid to reduce perioperative blood loss for total hip replacement [Z]. Proceedings of 2016 Annual Conference of Orthopedics Branch of Chinese Research Association of Traditional Chinese Medicine. Shanghai. 2016:448. 36. Dong Q Zhang Y Sun X The effectiveness and safety of aminocaproic acid for reducing blood loss in total knee and hip arthroplasty: a meta-analysis Int J Surg 2018 52 156 163 10.1016/j.ijsu.2018.02.035 29471157