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Bone & Joint Research
Vol. 8, Issue 1 | Pages 11 - 18
1 Jan 2019
McLean M McCall K Smith IDM Blyth M Kitson SM Crowe LAN Leach WJ Rooney BP Spencer SJ Mullen M Campton JL McInnes IB Akbar M Millar NL

Objectives. Tranexamic acid (TXA) is an anti-fibrinolytic medication commonly used to reduce perioperative bleeding. Increasingly, topical administration as an intra-articular injection or perioperative wash is being administered during surgery. Adult soft tissues have a poor regenerative capacity and therefore damage to these tissues can be harmful to the patient. This study investigated the effects of TXA on human periarticular tissues and primary cell cultures using clinically relevant concentrations. Methods. Tendon, synovium, and cartilage obtained from routine orthopaedic surgeries were used for ex vivo and in vitro studies using various concentrations of TXA. The in vitro effect of TXA on primary cultured tenocytes, fibroblast-like synoviocytes, and chondrocytes was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assays, fluorescent microscopy, and multi-protein apoptotic arrays for cell death. Results. There was a significant (p < 0.01) increase in cell death within all tissue explants treated with 100 mg/ml TXA. MTT assays revealed a significant (p < 0.05) decrease in cell viability in all tissues following treatment with 50 mg/ml or 100 mg/ml of TXA within four hours. There was a significant (p < 0.05) increase in cell apoptosis after one hour of exposure to TXA (100 mg/ml) in all tissues. Conclusion. The current study demonstrates that TXA caused significant periarticular tissue toxicity ex vivo and in vitro at commonly used clinical concentrations. Cite this article: M. McLean, K. McCall, I. D. M. Smith, M. Blyth, S. M. Kitson, L. A. N. Crowe, W. J. Leach, B. P. Rooney, S. J. Spencer, M. Mullen, J. L. Campton, I. B. McInnes, M. Akbar, N. L. Millar. Tranexamic acid toxicity in human periarticular tissues. Bone Joint Res 2019;8:11–18. DOI: 10.1302/2046-3758.81.BJR-2018-0181.R1


The Bone & Joint Journal
Vol. 101-B, Issue 6_Supple_B | Pages 104 - 109
1 Jun 2019
Hines JT Hernandez NM Amundson AW Pagnano MW Sierra RJ Abdel MP

Aims. Tranexamic acid (TXA) has been shown to significantly reduce transfusion rates in primary total hip arthroplasties (THAs), but high-quality evidence is limited in the revision setting. The purpose of the current study was to compare the rate of blood transfusions and symptomatic venous thromboembolic events (VTEs) in a large cohort of revision THAs treated with or without intravenous (IV) TXA. Patients and Methods. We performed a retrospective review of 3264 revision THAs (2645 patients) between 2005 and 2014, of which 1142 procedures received IV TXA (1 g at incision and 1 g at closure). The mean age in the revision group with TXA was 65 years (28 to 95), with 579 female patients (51%). The mean age in the revision group treated without TXA was 67 years (21 to 98), with 1160 female patients (55%). Outcomes analyzed included rates of transfusion and symptomatic VTEs between procedures undertaken with and without TXA. These comparisons were performed for the overall cohort, as well as within cases subcategorized for aseptic or septic aetiologies. A propensity score was developed to minimize bias between groups and utilized age at revision THA, sex, body mass index, American Society of Anesthesiologists (ASA) score, preoperative anticoagulation, and year of surgery. Results. Tranexamic acid significantly and substantially reduced the rate of blood transfusions after revision THA overall from 54% to 26% (p < 0.001; adjusted relative risk (RR) 1.6; 95% confidence interval (CI) 1.3 to 1.9), with a significant reduction in both aseptic (49% to 18%; p < 0.001) and septic (73% to 53%; p = 0.04) revisions. The rate of VTE was minimal overall, with three events (0.3%) in the TXA group and four events (0.2%) in the non-TXA group. There were no significant differences in VTE rates based on TXA use or aetiology of revision. Conclusion. Intravenous TXA significantly reduced transfusion rates during all-cause revision THAs, including a subgroup analysis of both aseptic and septic cohorts. Adjusted risk using propensity modelling showed no statistical difference in rates of VTEs between either group. Cite this article: Bone Joint J 2019;100-B(6 Supple B):104–109


Objectives. Tranexamic acid (TXA) is an antifibrinolytic agent used as a blood-sparing technique in total knee arthroplasty (TKA), and is routinely administered by intravenous (IV) or intra-articular (IA) injection. Recently, a novel method of TXA administration, the combined IV and IA application of TXA, has been applied in TKA. However, the scientific evidence of combined administration of TXA in TKA is still meagre. This meta-analysis aimed to investigate the efficacy and safety of combined IV and IA TXA in patients undergoing TKA. Materials and Methods. A systematic search was carried out in PubMed, the Cochrane Clinical Trial Register (Issue12 2015), Embase, Web of Science and the Chinese Biomedical Database. Only randomised controlled trials (RCT) evaluating the efficacy and safety of combined use TXA in TKA were identified. Two authors independently identified the eligible studies, extracted data and assessed the methodological quality of included studies. Meta-analysis was conducted using Review Manager 5.3 software. Results. A total of ten RCTs (1143 patients) were included in this study. All the included studies were randomised and the quality of included studies still needed improvement. The results indicated that, compared with either placebo or the single-dose TXA (IV or IA) group, the combination of IV and IA TXA group had significantly less total blood loss, hidden blood loss, total drain output, a lower transfusion rate and a lower drop in haemoglobin level. There were no statistically significant differences in complications such as wound infection and deep vein thrombosis between the combination group and the placebo or single-dose TXA group. Conclusions. Compared with placebo or the single-dose TXA, the combined use of IV and IA TXA provided significantly better results with respect to all outcomes related to post-operative blood loss without increasing the risk of thromboembolic complications in TKA. Cite this article: Z. F. Yuan, H. Yin, W. P. Ma, D. L. Xing. The combined effect of administration of intravenous and topical tranexamic acid on blood loss and transfusion rate in total knee arthroplasty: combined tranexamic acid for TKA. Bone Joint Res 2016;5:353–361. DOI: 10.1302/2046-3758.58.BJR-2016-0001.R2


The Bone & Joint Journal
Vol. 103-B, Issue 3 | Pages 449 - 455
1 Mar 2021
Viberg B Gundtoft PH Schønnemann JO Pedersen L Andersen LR Titlestad K Madsen CF Clemmensen SB Halekoh U Lauritsen J Overgaard S

Aims. To assess the safety of tranexamic acid (TXA) in a large cohort of patients aged over 65 years who have sustained a hip fracture, with a focus on transfusion rates, mortality, and thromboembolic events. Methods. This is a consecutive cohort study with prospectively collected registry data. Patients with a hip fracture in the Region of Southern Denmark were included over a two-year time period (2015 to 2017) with the first year constituting a control group. In the second year, perioperative TXA was introduced as an intervention. Outcome was transfusion frequency, 30-day and 90-day mortality, and thromboembolic events. The latter was defined as any diagnosis or death due to arterial or venous thrombosis. The results are presented as relative risk (RR) and hazard ratio (HR) with 95% confidence intervals (CIs). Results. A total of 3,097 patients were included: 1,558 in the control group and 1,539 in the TXA group.31% (n = 477) of patients had transfusions in the control group compared to 27% (n = 405) in the TXA group yielding an adjusted RR of 0.83 (95% CI 0.75 to 0.91). TXA was not associated with increased 30-day mortality with an adjusted HR of 1.10 (95% CI 0.88 to 1.39) compared to the control group as well as no association with increased risk of 90-day mortality with a per protocol adjusted HR of 1.24 (95% CI 0.93 to 1.66). TXA was associated with a lower risk of thromboembolic events after 30 days (RR 0.63 (95% CI 0.42 to 0.93)) and 90 days (RR 0.72 (95% CI 0.52 to 0.99)). A subanalysis on haemoglobin demonstrated a median 17.7 g/L (interquartile range (IQR) 11.3 to 27.3) decrease in the control group compared to 17.7 g/L (IQR 9.7 to 25.8) in the per protocol TXA group (p = 0.060 on group level difference). Conclusion. TXA use in patients with a hip fracture, was not associated with an increased risk of mortality but was associated with lower transfusion rate and reduced thromboembolic events. Thus, we conclude that it is safe to use TXA in this patient group. Cite this article: Bone Joint J 2021;103-B(3):449–455


Bone & Joint Research
Vol. 6, Issue 8 | Pages 499 - 505
1 Aug 2017
Morrison RJM Tsang B Fishley W Harper I Joseph JC Reed MR

Objectives. We have increased the dose of tranexamic acid (TXA) in our enhanced total joint recovery protocol at our institution from 15 mg/kg to 30 mg/kg (maximum 2.5 g) as a single, intravenous (IV) dose. We report the clinical effect of this dosage change. Methods. We retrospectively compared two cohorts of consecutive patients undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA) surgery in our unit between 2008 and 2013. One group received IV TXA 15 mg/kg, maximum 1.2 g, and the other 30 mg/kg, maximum 2.5 g as a single pre-operative dose. The primary outcome for this study was the requirement for blood transfusion within 30 days of surgery. Secondary measures included length of hospital stay, critical care requirements, re-admission rate, medical complications and mortality rates. Results. A total of 1914 THA and 2537 TKA procedures were evaluated. In THA, the higher dose of TXA was associated with a significant reduction in transfusion (p = 0.02, risk ratio (RR) 0.74, 95% confidence interval (CI) 0.58 to 0.96) and rate of re-admission (p < 0.001, RR 0.50, 95% CI 0.35 to 0.71). There were reductions in the requirement for critical care (p = 0.06, RR 0.55, 95% CI 0.31 to 1.00), and in the length of stay from 4.7 to 4.3 days (p = 0.02). In TKA, transfusion requirements (p = 0.049, RR 0.64, 95% CI 0.41 to 0.99), re-admission rate (p = 0.001, RR 0.56, 95% CI 0.39 to 0.80) and critical care requirements (p < 0.003, RR 0.34, 95% CI 0.16 to 0.72) were reduced with the higher dose. Mean length of stay reduced from 4.6 days to 3.6 days (p < 0.01). There was no difference in the incidence of deep vein thrombosis, pulmonary embolism, gastrointestinal bleed, myocardial infarction, stroke or death in THA and TKA between cohorts. Conclusion. We suggest that a single pre-operative dose of TXA, 30 mg/kg, maximum 2.5g, results in a lower transfusion requirement compared with a lower dose in patients undergoing elective primary hip and knee arthroplasty. However, these findings should be interpreted in the context of the retrospective non-randomised study design. Cite this article: R. J. M. Morrison, B. Tsang, W. Fishley, I. Harper, J. C. Joseph, M. R. Reed. Dose optimisation of intravenous tranexamic acid for elective hip and knee arthroplasty: The effectiveness of a single pre-operative dose. Bone Joint Res 2017;6:499–505. DOI: 10.1302/2046-3758.68.BJR-2017-0005.R1


The Bone & Joint Journal
Vol. 100-B, Issue 3 | Pages 404 - 412
1 Mar 2018
Parker JD Lim KS Kieser DC Woodfield TBF Hooper GJ

Aims. The intra-articular administration of tranexamic acid (TXA) has been shown to be effective in reducing blood loss in unicompartmental knee arthroplasty and anterior cruciate reconstruction. The effects on human articular cartilage, however, remains unknown. Our aim, in this study, was to investigate any detrimental effect of TXA on chondrocytes, and to establish if there was a safe dose for its use in clinical practice. The hypothesis was that TXA would cause a dose-dependent damage to human articular cartilage. . Materials and Methods. The cellular morphology, adhesion, metabolic activity, and viability of human chondrocytes when increasing the concentration (0 mg/ml to 40 mg/ml) and length of exposure to TXA (0 to 12 hours) were analyzed in a 2D model. This was then repeated, excluding cellular adhesion, in a 3D model and confirmed in viable samples of articular cartilage. Results. Increasing concentrations above 20 mg/ml resulted in atypical morphology, reduced cellular adhesion and metabolic activity associated with increased chondrocyte death. However, the cell matrix was not affected by the concentration of TXA or the length of exposure, and offered cellular protection for concentrations below 20 mg/ml. Conclusion. These results show that when in vitro chondrocytes are exposed to higher concentrations of TXA, such as that expected following recommended intra-articular administration, cytotoxicity is observed. This effect is dose-dependent, such that a tissue concentration of 10 mg/ml to 20 mg/ml could be expected to be safe. Cite this article: Bone Joint J 2018;100-B:404–12


Bone & Joint Open
Vol. 3, Issue 7 | Pages 536 - 542
11 Jul 2022
Karayiannis PN Agus A Bryce L Hill JC Beverland D

Aims. Tranexamic acid (TXA) is now commonly used in major surgical operations including orthopaedics. The TRAC-24 randomized control trial (RCT) aimed to assess if an additional 24 hours of TXA postoperatively in primary total hip (THA) and total knee arthroplasty (TKA) reduced blood loss. Contrary to other orthopaedic studies to date, this trial included high-risk patients. This paper presents the results of a cost analysis undertaken alongside this RCT. Methods. TRAC-24 was a prospective RCT on patients undergoing TKA and THA. Three groups were included: Group 1 received 1 g intravenous (IV) TXA perioperatively and an additional 24-hour postoperative oral regime, Group 2 received only the perioperative dose, and Group 3 did not receive TXA. Cost analysis was performed out to day 90. Results. Group 1 was associated with the lowest mean total costs, followed by Group 2 and then Group 3. The differences between Groups 1 and 3 (-£797.77 (95% confidence interval -1,478.22 to -117.32) were statistically significant. Extended oral dosing reduced costs for patients undergoing THA but not TKA. The reduced costs in Groups 1 and 2 resulted from reduced length of stay, readmission rates, emergency department attendances, and blood transfusions. Conclusion. This study demonstrated significant cost savings when using TXA in primary THA or TKA. Extended oral dosing reduced costs further in THA but not TKA. Cite this article: Bone Jt Open 2022;3(7):536–542


The Bone & Joint Journal
Vol. 102-B, Issue 9 | Pages 1151 - 1157
14 Sep 2020
Levack AE McLawhorn AS Dodwell E DelPizzo K Nguyen J Sink E

Aims. Tranexamic acid (TXA) has been shown to reduce blood loss and transfusion requirements in patients undergoing orthopaedic surgery. There remains a lack of prospective evidence for the use of TXA in patients undergoing periacetabular osteotomy (PAO). The purpose of this study was to determine if intravenous (IV) TXA is effective in reducing calculated blood loss and transfusions after PAO. Methods. This was a single-centre prospective double-blind placebo-controlled randomized trial of 81 patients aged 12 to 45 years undergoing elective PAO by a single surgeon. The intervention group (n = 40) received two doses of IV TXA of a maximum 1 g in each dose; the control group (n = 41) received two doses of 50 ml 0.9% saline IV. The primary outcome was perioperative calculated blood loss. Secondary outcomes included allogenic transfusions and six-week postoperative complications. Results. There were no differences in demographics or intraoperative variables between study groups. The TXA group demonstrated lower mean calculated blood loss (1,265 ml, (SD 321) vs 1,515 ml, (SD 394); p = 0.002) and lower frequency of allogenic transfusion (10%/n = 4 vs 37%/n = 15; p = 0.008). Regression analyses associated TXA use with significant reductions in calculated blood loss (p < 0.001) and transfusion (p = 0.007) after adjusting for age, sex, body mass index, preoperative haemoglobin, cell-saver volume, intraoperative mean arterial blood pressure, and operating time. No patients suffered venous thromboembolic complications. Conclusion. In this trial, IV TXA decreased postoperative calculated blood loss by 293 ml and reduced the frequency of allogenic transfusions by 73% (37% vs 10%) following PAO. TXA may be safe and effective for reducing blood loss in patients undergoing PAO. Cite this article: Bone Joint J 2020;102-B(9):1151–1157


The Bone & Joint Journal
Vol. 101-B, Issue 7_Supple_C | Pages 10 - 16
1 Jul 2019
Fillingham YA Darrith B Calkins TE Abdel MP Malkani AL Schwarzkopf R Padgett DE Culvern C Sershon RA Bini S Della Valle CJ

Aims. Tranexamic acid (TXA) is proven to reduce blood loss following total knee arthroplasty (TKA), but there are limited data on the impact of similar dosing regimens in revision TKA. The purpose of this multicentre randomized clinical trial was to determine the optimal regimen to maximize the blood-sparing properties of TXA in revision TKA. Patients and Methods. From six-centres, 233 revision TKAs were randomized to one of four regimens: 1 g of intravenous (IV) TXA given prior to the skin incision, a double-dose regimen of 1 g IV TXA given both prior to skin incision and at time of wound closure, a combination of 1 g IV TXA given prior to skin incision and 1 g of intraoperative topical TXA, or three doses of 1950 mg oral TXA given two hours preoperatively, six hours postoperatively, and on the morning of postoperative day one. Randomization was performed based on the type of revision procedure to ensure equivalent distribution among groups. Power analysis determined that 40 patients per group were necessary to identify a 1 g/dl difference in the reduction of haemoglobin postoperatively between groups with an alpha of 0.05 and power of 0.80. Per-protocol analysis involved regression analysis and two one-sided t-tests for equivalence. Results. In total, one patient withdrew, five did not undergo surgery, 16 were screening failures, and 25 did not receive the assigned treatment, leaving 186 patients for analysis. There was no significant difference in haemoglobin reduction among treatments (2.8 g/dl for single-dose IV TXA, 2.6 g/dl for double-dose IV TXA, 2.6 g/dl for combined IV/topical TXA, 2.9 g/dl for oral TXA; p = 0.38). Similarly, calculated blood loss (p = 0.65) and transfusion rates (p = 0.95) were not significantly different between groups. Equivalence testing assuming a 1 g/dl difference in haemoglobin change as clinically relevant showed that all possible pairings were statistically equivalent. Conclusion. Despite the higher risk of blood loss in revision TKA, all TXA regimens tested had equivalent blood-sparing properties. Surgeons should consider using the lowest effective dose and least costly TXA regimen in revision TKA. Cite this article: Bone Joint J 2019;101-B(Supple 7):10–16


Bone & Joint Research
Vol. 10, Issue 6 | Pages 354 - 362
1 Jun 2021
Luo Y Zhao X Yang Z Yeersheng R Kang P

Aims. The purpose of this study was to examine the efficacy and safety of carbazochrome sodium sulfonate (CSS) combined with tranexamic acid (TXA) on blood loss and inflammatory responses after primary total hip arthroplasty (THA), and to investigate the influence of different administration methods of CSS on perioperative blood loss during THA. Methods. This study is a randomized controlled trial involving 200 patients undergoing primary unilateral THA. A total of 200 patients treated with intravenous TXA were randomly assigned to group A (combined intravenous and topical CSS), group B (topical CSS), group C (intravenous CSS), or group D (placebo). Results. Mean total blood loss (TBL) in groups A (605.0 ml (SD 235.9)), B (790.9 ml (SD 280.7)), and C (844.8 ml (SD 248.1)) were lower than in group D (1,064.9 ml (SD 318.3), p < 0.001). We also found that compared with group D, biomarker level of inflammation, transfusion rate, pain score, and hip range of motion at discharge in groups A, B, and C were significantly improved. There were no differences among the four groups in terms of intraoperative blood loss (IBL), intramuscular venous thrombosis (IMVT), and length of hospital stay (LOS). Conclusion. The combined application of CSS and TXA is more effective than TXA alone in reducing perioperative blood loss and transfusion rates, inflammatory response, and postoperative hip pain, results in better early hip flexion following THA, and did not increase the associated venous thromboembolism (VTE) events. Intravenous combined with topical injection of CSS was superior to intravenous or topical injection of CSS alone in reducing perioperative blood loss. Cite this article: Bone Joint Res 2021;10(6):354–362


The Bone & Joint Journal
Vol. 100-B, Issue 2 | Pages 152 - 160
1 Feb 2018
Subramanyam KN Khanchandani P Tulajaprasad PV Jaipuria J Mundargi AV

Aims. The aims of this study were to compare the efficacy and safety of intra-articular and intravenous (IV) tranexamic acid (TXA) in controlling perioperative blood loss in total knee arthroplasty (TKA) using a randomized, double-blinded equivalence trial. Patients and Methods. A total of 182 patients aged between 45 and 75 years undergoing unilateral TKA at a tertiary centre were randomized to receive TXA, either 1.5 g intra-articularly after closure of the wound (n = 91) or two doses of 10 mg/kg IV (n = 91). The primary outcome measure was the reduction in the level of haemoglobin (Hb) in the blood on the fifth postoperative day. Secondary outcome measures were the total, visible, and hidden blood losses (TBL, VBL, HBL). We assumed equivalence of the primary outcome in both routes with a margin of ± 0.35gm/dl. Block randomization using computer-generated random numbers was used. The patients and the assessor of outcome were blinded. Results. All patients completed the study. The mean difference in the reduction of the level of Hb between the two groups was -0.0055 gm/dl, with two-sided 95% confidence interval (CI) being -0.29 to 0.27, well within the predefined equivalence margin of ± 0.35gm/dl. The groups were comparable with regard to TBL, VBL, HBL, and complications. No patient needed a blood transfusion. Conclusion. A single intra-articular dose and two IV doses of TXA give equivalent efficacy and safety in the management of blood loss at TKA. Cite this article: Bone Joint J 2018;100-B:152–60


The Bone & Joint Journal
Vol. 98-B, Issue 6 | Pages 747 - 753
1 Jun 2016
Tengberg PT Foss NB Palm H Kallemose T Troelsen A

Aims. We chose unstable extra-capsular hip fractures as our study group because these types of fractures suffer the largest blood loss. We hypothesised that tranexamic acid (TXA) would reduce total blood loss (TBL) in extra-capsular fractures of the hip. . Patients and Methods. A single-centre placebo-controlled double-blinded randomised clinical trial was performed to test the hypothesis on patients undergoing surgery for extra-capsular hip fractures. For reasons outside the control of the investigators, the trial was stopped before reaching the 120 included patients as planned in the protocol. . Results. In all 72 patients (51 women, 21 men; 33 patients in the TXA group, 39 in the placebo group) were included in the final analysis, with a significant mean reduction of 570.8 ml (p = 0.029) in TBL from 2100.4 ml (standard deviation (. sd). = 1152.6) in the placebo group to 1529.6 ml (. sd. = 1012.7) in the TXA group. . The 90-day mortality was 27.2% (n = 9) in the TXA group and 10.2% (n = 4) in the placebo group (p = 0.07). We were not able to ascertain a reliable cause of death in these patients. . Discussion. TXA significantly reduced TBL in extra-capsular hip fractures, but concerns regarding its safety in this patient group must be investigated further before the use of TXA can be recommended. Take home message: We present a randomised clinical trial that is unique in the literature. We evaluate the effect of TXA in very homogenous population - extra-capsular fractures operated with short intramedullary nails. Cite this article: Bone Joint J 2016;98-B:747–53


The Bone & Joint Journal
Vol. 96-B, Issue 8 | Pages 1005 - 1015
1 Aug 2014
Alshryda S Sukeik M Sarda P Blenkinsopp J Haddad FS Mason JM

Intravenous tranexamic acid (TXA) has been shown to be effective in reducing blood loss and the need for transfusion after joint replacement. Recently, there has been interest in applying it topically before the closure of surgical wounds. This has the advantages of ease of application, maximum concentration at the site of bleeding, minimising its systemic absorption and, consequently, concerns about possible side-effects. We conducted a systematic review and meta-analysis which included 14 randomised controlled trials (11 in knee replacement, two in hip replacement and one in both) which investigated the effect of topical TXA on blood loss and rates of transfusion. Topical TXA significantly reduced the rate of blood transfusion (total knee replacement: risk ratio (RR) 4.51; 95% confidence interval (CI): 3.02 to 6.72; p < 0.001 (nine trials, I. 2 . = 0%); total hip replacement: RR 2.56; 95% CI: 1.32 to 4.97, p = 0.004 (one trial)). The rate of thromboembolic events with topical TXA were similar to those found with a placebo. Indirect comparison of placebo-controlled trials of topical and intravenous TXA indicates that topical administration is superior to the intravenous route. In conclusion, topical TXA is an effective and safe method of reducing the need for blood transfusion after total knee and hip replacement. Further research is required to find its optimum dose for topical use. Cite this article: Bone Joint J 2014;96-B:1005–15


The Bone & Joint Journal
Vol. 103-B, Issue 3 | Pages 442 - 448
1 Mar 2021
Nikolaou VS Masouros P Floros T Chronopoulos E Skertsou M Babis GC

Aims. The aim of this study was to investigate the hypothesis that a single dose of tranexamic acid (TXA) would reduce blood loss and transfusion rates in elderly patients undergoing surgery for a subcapital or intertrochanteric (IT) fracture of the hip. Methods. In this single-centre, randomized controlled trial, elderly patients undergoing surgery for a hip fracture, either hemiarthroplasty for a subcapital fracture or intramedullary nailing for an IT fracture, were screened for inclusion. Patients were randomly allocated to a study group using a sealed envelope. The TXA group consisted of 77 patients, (35 with a subcapital fracture and 42 with an IT fracture), and the control group consisted of 88 patients (29 with a subcapital fracture and 59 with an IT fracture). One dose of 15 mg/kg of intravenous (IV) TXA diluted in 100 ml normal saline (NS,) or one dose of IV placebo 100 ml NS were administered before the incision was made. The haemoglobin (Hb) concentration was measured before surgery and daily until the fourth postoperative day. The primary outcomes were the total blood loss and the rate of transfusion from the time of surgery to the fourth postoperative day. Results. Homogeneity with respect to baseline characteristics was ensured between groups. The mean total blood loss was significantly lower in patients who received TXA (902.4 ml (-279.9 to 2,156.9) vs 1,226.3 ml (-269.7 to 3,429.7); p = 0.003), while the likelihood of requiring a transfusion of at least one unit of red blood cells was reduced by 22%. Subgroup analysis showed that these differences were larger in patients who had an IT fracture compared with those who had a subcapital fracture. Conclusion. Elderly patients who undergo intramedullary nailing for an IT fracture can benefit from a single dose of 15 mg/kg TXA before the onset of surgery. A similar tendency was identified in patients undergoing hemiarthroplasty for a subcapital fracture but not to a statistically significant level. Cite this article: Bone Joint J 2021;103-B(3):442–448


The Bone & Joint Journal
Vol. 101-B, Issue 2 | Pages 207 - 212
1 Feb 2019
Clavé A Gérard R Lacroix J Baynat C Danguy des Déserts M Gatineau F Mottier D

Aims. Cementless primary total hip arthroplasty (THA) is associated with risks of bleeding and thromboembolism. Anticoagulants are effective as venous thromboprophylaxis, but with an increased risk of bleeding. Tranexamic acid (TXA) is an efficient antifibrinolytic agent, but the mode and timing of its administration remain controversial. This study aimed to determine whether two intravenous (IV) TXA regimens (a three-hour two-dose (short-TXA) and 11-hour four-dose (long-TXA)) were more effective than placebo in reducing perioperative real blood loss (RBL, between baseline and day 3 postoperatively) in patients undergoing THA who receive rivaroxaban as thromboprophylaxis. The secondary aim was to assess the non-inferiority of the reduction of blood loss of the short protocol versus the long protocol. Patients and Methods. A multicentre, prospective, randomized, double-blind, placebo-controlled trial was undertaken involving 229 patients undergoing primary cementless THA using a posterior approach, whose extended rivaroxaban thromboprophylaxis started on the day of surgery. There were 98 male and 131 female patients, with a mean age of 65.5 years (32 to 91). The primary outcome, perioperative RBL, was evaluated at 72 hours postoperatively. The efficacy of short- and long-TXA protocols in the reduction of perioperative RBL was compared with a placebo group. Results. TXA significantly reduced perioperative blood loss compared with placebo (p < 0.001); the mean differences were 525.3 ml (short-TXA vs placebo) and 550.1 ml (long-TXA vs placebo). No venous or arterial thromboembolic complications were reported. The upper boundary of the 95% confidence interval, when comparing short and long protocols, was below the pre-specified margin of non-inferiority (p = 0.027). Conclusion. In patients undergoing primary cementless THA, using a posterior approach, who are treated with rivaroxaban for thromboembolic prophylaxis, short- and long-TXA IV protocols are significantly more effective than placebo in reducing perioperative RBL, without any thromboembolic complications. Non-inferiority of a short- versus a long-TXA protocol in reducing perioperative RBL was supported in a secondary analysis


The Bone & Joint Journal
Vol. 97-B, Issue 7 | Pages 905 - 910
1 Jul 2015
Hsu C Lin P Kuo F Wang J

Tranexamic acid (TXA), an inhibitor of fibrinolysis, reduces blood loss after total knee arthroplasty. However, its effect on minimally invasive total hip arthroplasty (THA) is not clear. We performed a prospective, randomised double-blind study to evaluate the effect of two intravenous injections of TXA on blood loss in patients undergoing minimally invasive THA. In total, 60 patients (35 women and 25 men with a mean age of 58.1 years; 17 to 84) who underwent unilateral minimally invasive uncemented THA were randomly divided into the study group (30 patients, 20 women and ten men with a mean age of 56.5 years; 17 to 79) that received two intravenous injections 1 g of TXA pre- and post-operatively (TXA group), and a placebo group (30 patients, 15 women and 15 men with a mean age of 59.5 years; 23 to 84). We compared the peri-operative blood loss of the two groups. Actual blood loss was calculated from the maximum reduction in the level of haemoglobin. All patients were followed clinically for the presence of venous thromboembolism. The TXA group had a lower mean intra-operative blood loss of 441 ml (150 to 800) versus 615 ml (50 to 1580) in the placebo (p = 0.044), lower mean post-operative blood loss (285 ml (120 to 570) versus 392 ml (126 to 660) (p = 0.002), lower mean total blood loss (1070 ml (688 to 1478) versus 1337 ml (495 to 2238) (p = 0.004) and lower requirement for transfusion (p = 0.021). No patients in either group had symptoms of venous thromboembolism or wound complications. . This prospective, randomised controlled study showed that a regimen of two intravenous injections of 1 g TXA is effective for blood conservation after minimally invasive THA. Cite this article: Bone Joint J 2015;97-B:905–10


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 6 | Pages 776 - 783
1 Jun 2009
Rajesparan K Biant LC Ahmad M Field RE

Tranexamic acid is a fibrinolytic inhibitor which reduces blood loss in total knee replacement. We examined the effect on blood loss of a standardised intravenous bolus dose of 1 g of tranexamic acid, given at the induction of anaesthesia in patients undergoing total hip replacement and tested the potential prothrombotic effect by undertaking routine venography. In all, 36 patients received 1 g of tranexamic acid, and 37 no tranexamic acid. Blood loss was measured directly per-operatively and indirectly post-operatively. Tranexamic acid reduced the early post-operative blood loss and total blood loss (p = 0.03 and p = 0.008, respectively) but not the intraoperative blood loss. The tranexamic acid group required fewer transfusions (p = 0.03) and had no increased incidence of deep-vein thrombosis. The reduction in early post-operative blood loss was more marked in women (p = 0.05), in whom this effect was dose-related (r = −0.793). Our study showed that the administration of a standardised pre-operative bolus of 1 g of tranexamic acid was cost-effective in reducing the blood loss and transfusion requirements after total hip replacement, especially in women


The Bone & Joint Journal
Vol. 98-B, Issue 2 | Pages 173 - 178
1 Feb 2016
Sassoon A Nam D Jackups R Johnson SR Nunley RM Barrack RL

Aims. This study investigated whether the use of tranexamic acid (TXA) decreased blood loss and transfusion related cost following surface replacement arthroplasty (SRA). . Methods. A retrospective review of patients treated with TXA during a SRA, who did not receive autologous blood (TXA group) was performed. Two comparison groups were established; the first group comprised of patients who donated their own blood pre-operatively (auto group) and the second of patients who did not donate blood pre-operatively (control). Outcomes included transfusions, post-operative haemoglobin (Hgb), complications, and length of post-operative stay. . Results. Between 2009 and 2013, 150 patients undergoing SRA were identified for inclusion: 51 in the auto, 49 in the control, and 50 in the TXA group. There were no differences in the pre-operative Hgb concentrations between groups. The mean post-operative Hgb was 11.3 g/dL (9.1 to 13.6) in the auto and TXA groups, and 10.6 g/dL (8.1 to 12.1)in the control group (p = 0.001). Accounting for cost of transfusions, administration of TXA, and length of stay, the cost per patient was $1731, $339, and $185 for the auto, control and TXA groups, respectively. . Discussion. TXA use demonstrated higher post-operative Hgb concentrations when compared with controls and decreased peri-operative costs. Take home message: Tranexamic acid safely limits allogeneic transfusion, maintains post-operative haemoglobin, and decreases direct and indirect transfusion related costs in surface replacement arthroplasty. Cite this article: Bone Joint J 2016;98-B:173–8


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 3 | Pages 306 - 309
1 Mar 2007
Molloy DO Archbold HAP Ogonda L McConway J Wilson RK Beverland DE

We performed a randomised, controlled trial involving 150 patients with a pre-operative level of haemoglobin of 13.0 g/dl or less, to compare the effect of either topical fibrin spray or intravenous tranexamic acid on blood loss after total knee replacement. A total of 50 patients in the topical fibrin spray group had 10 ml of the reconstituted product applied intra-operatively to the operation site. The 50 patients in the tranexamic acid group received 500 mg of tranexamic acid intravenously five minutes before deflation of the tourniquet and a repeat dose three hours later, and a control group of 50 patients received no pharmacological intervention. There was a significant reduction in the total calculated blood loss for those in the topical fibrin spray group (p = 0.016) and tranexamic acid group (p = 0.041) compared with the control group, with mean losses of 1190 ml (708 to 2067), 1225 ml (580 to 2027), and 1415 ml (801 to 2319), respectively. The reduction in blood loss in the topical fibrin spray group was not significantly different from that achieved in the tranexamic acid group (p = 0.72)


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 9 | Pages 1141 - 1142
1 Sep 2006
Phillips SJ Chavan R Porter ML Kay PR Hodgkinson JP Purbach B Reddick AH Frayne JM

We carried out a retrospective case-control study in 80 patients who underwent a revision total hip replacement. Group A (40 patients) received tranexamic acid and intra-operative cell salvage. Group B (40 patients) was a matched control group and did not receive this management. Each group was divided into four subgroups: revision of both components, revision of both components with bone grafting, revision of the acetabular component with or without bone graft, and revision of the femoral component with or without bone graft. In group A the total number of units transfused was 52, compared with 139 in group B, representing a reduction in blood usage of 62.5%. The mean amount of blood transfused from cell salvage in each group was 858 ml (113 to 2100), 477 ml (0 to 2680), 228 ml (75 to 315) and 464 ml (120 to 1125), respectively. There was a significant difference in the amount of blood returned between the groups (p < 0.0001). In group A, 22 patients needed transfusion and in group B, 37 (p < 0.0001). A cost analysis calculation showed a total revenue saving of £70 000 and a potential saving throughout our facility of £318 288 per year. Our results show that a significant reduction in blood transfusion can be made using combined cell salvage and tranexamic acid in revision surgery of the hip