Aims. Antifibrinolytic agents, including tranexamic acid (TXA) and epsilon-aminocaproic acid (EACA), have been shown to be safe and effective for decreasing perioperative blood loss and transfusion following total hip arthroplasty (THA) and total knee arthroplasty (TKA). However, there are few prospective studies that directly compare these agents. The purpose of this study was to compare the benefits of intraoperative intravenous TXA with EACA. Patients and Methods. A total of 235 patients (90 THA and 145 TKA) were enrolled in this prospective, randomized controlled trial at a single tertiary-care referral centre. In the THA cohort, 53.3% of the patients were female with a median age of 59.8 years (interquartile range (IQR) 53.3 to 68.1). In the TKA cohort, 63.4% of the patients were female with a median age of 65.1 years (IQR 59.4 to 69.5). Patients received either TXA (n = 119) or EACA (n = 116) in two doses intraoperatively. The primary outcome measures included change in haemoglobin level and blood volume, postoperative drainage, and rate of transfusion. Secondary outcome measures included postoperative complications, cost, and length of stay (LOS). Results. TKA patients who received EACA had greater drainage (median 320 ml (IQR 185 to 420) vs 158 ml (IQR 110 to 238); p < 0.001), increased loss of blood volume (891 ml (IQR 612 to 1203) vs 661 ml (IQR 514 to 980); p = 0.014), and increased haemoglobin change from the preoperative level (2.1 ml (IQR 1.7 to 2.8) vs 1.9 ml (IQR 1.2 to 2.4); p = 0.016) compared with patients who received TXA. For the THA cohort, no statistically significant differences were observed in any haematological outcome measure. One patient in the EACA group required transfusion. No patient in the TXA group required transfusion. There were no statistically significant differences in number or type of postoperative complications or LOS for either THA or TKA patients regardless of whether they received TXA or EACA. Conclusion. For hip and knee arthroplasty procedures, EACA is associated with increased perioperative blood loss compared with TXA. However, there is no significant difference in transfusion rate. While further prospective studies are needed to compare the efficacy of each agent, we currently recommend orthopaedic surgeons to select their antifibrinolytic based on cost and regional availability. Cite this article: Bone Joint J 2019;101-B:1093–1099

We investigated the effect of a fibrinolytic inhibitor, tranexamic acid, on blood loss and blood transfusion in knee arthroplasty by a randomised, double-blind study of 86 patients. A dose of 10 mg/kg body-weight of either tranexamic acid or placebo was given intravenously shortly before the release of the tourniquet, and repeated three hours later. The mean total blood loss was 730 ± 280 ml in the tranexamic acid group as against 1410 ± 480 ml in the placebo group (p < 0.001). Both the number of patients receiving blood transfusion and the number of blood units transfused were reduced to one-third in the treated group, and mean postoperative Hb concentrations were significantly higher after prophylaxis. The number of thromboembolic complications was the same in both groups. Tranexamic acid should be given prophylactically in order to be effective

We report a systematic review and meta-analysis of published randomised controlled trials evaluating the efficacy of tranexamic acid (TXA) in reducing blood loss and transfusion in total hip replacement (THR). The data were evaluated using the generic evaluation tool designed by the Cochrane Bone, Joint and Muscle Trauma Group. We identified 11 clinical trials which were suitable for detailed extraction of data. There were no trials that used TXA in revision THR. A total of seven studies (comprising 350 patients) were eligible for the blood loss outcome data. The use of TXA reduced intra-operative blood loss by a mean of 104 ml (95% confidence interval (CI) −164 to −44, p = 0.0006, heterogeneity I. 2. 0%), postoperative blood loss by a mean of 172 ml (95% CI −263 to −81, p = 0.0002, heterogeneity I. 2. 63%) and total blood loss by a mean of 289 ml (95% CI −440 to −138, p < 0.0002, heterogeneity I. 2. 54%). TXA led to a significant reduction in the proportion of patients requiring allogeneic blood transfusion (risk difference −0.20, 95% CI −0.29 to −0.11, p < 0.00001, I. 2. 15%). There were no significant differences in deep-vein thrombosis, pulmonary embolism, infection rates or other complications among the study groups

Aims. A typical pattern of blood loss associated with total hip arthroplasty (THA) is 200 ml intraoperatively and 1.3 l in the first 48 postoperative hours. Tranexamic acid (TXA) is most commonly given as a single preoperative dose only and is often withheld from patients with a history of thromboembolic disease as they are perceived to be “high-risk” with respect to postoperative venous thromboembolism (VTE). The TRanexamic ACid for 24 hours trial (TRAC-24) aimed to identify if an additional 24-hour postoperative TXA regime could further reduce blood loss beyond a once-only dose at the time of surgery, without excluding these high-risk patients. Methods. TRAC-24 was a prospective, phase IV, single centre, open label, parallel group, randomized controlled trial (RCT) involving patients undergoing primary unilateral elective THA. The primary outcome measure was the indirect calculated blood loss (IBL) at 48 hours. The patients were randomized into three groups. Group 1 received 1 g intravenous (IV) TXA at the time of surgery and an additional oral regime for 24 hours postoperatively, group 2 only received the intraoperative dose, and group 3 did not receive any TXA. Results. A total of 534 patients were randomized, with 233 in group 1, 235 in group 2, and 66 in group 3; 92 patients (17.2%) were considered high-risk. The mean IBL did not differ significantly between the two intervention groups (848.4 ml (SD 463.8) for group 1, and 843.7 ml (SD 478.7) for group 2; mean difference -4.7 ml (95% confidence interval -82.9 to 92.3); p = 0.916). No differences in mortality or incidence of VTE were observed between any group. Conclusion. The addition of oral TXA for 24 hours postoperatively does not reduce blood loss beyond that achieved with a single 1 g IV perioperative dose alone. There may be a clinically relevant difference in patients with a normal BMI, which warrants further investigation. Critically, there were no safety issues in patients with a history of thromboembolic, cardiovascular, or cerebrovascular disease. Cite this article: Bone Joint J 2021;103-B(7):1197–1205

Tranexamic acid (TXA) has been used to reduce blood loss during total hip arthroplasty (THA), but its use could increase the risk of venous thromboembolic disease (VTE). Several studies have reported that TXA does not increase the prevalence of deep vein thrombosis (DVT), but most of those used routine chemical thromboprophylaxis, thereby masking the potential increased risk of TXA on VTE. We wished to ascertain whether TXA increases the prevalence of VTE in patients undergoing THA without routine chemical thromboprophylaxis. We carried out a retrospective case-control study in 254 patients who underwent a primary THA, 127 of whom received TXA (1 g given pre-operatively) and a control group of 127 who did not. All patients had mechanical but no chemical thomboprophylaxis. Each patient was examined for DVT by bilateral ultrasonography pre-operatively and on post-operative days 1 and 7. TXA was found to statistically significantly increase the incidence of total DVT on post-operative day 7 compared with the control group (24 (18.9%) and 12 (9.4%), respectively; p < 0.05) but most cases of DVT were isolated distal DVT, with the exception of one patient with proximal DVT in each group. One patient in the control group developed a non-fatal symptomatic pulmonary embolism (PE). The use of TXA did not appear to affect the prevalence of either proximal DVT or PE. Cite this article: Bone Joint J 2015; 97-B:458–62

Aims. The aim of this study was to identify the most effective regimen of multiple doses of oral tranexamic acid (TXA) in achieving maximum reduction of blood loss in total knee arthroplasty (TKA). Patients and Methods. In this randomized controlled trial, 200 patients were randomized to receive a single dose of 2.0 g of TXA orally two hours preoperatively (group A), a single dose of TXA followed by 1.0 g orally three hours postoperatively (group B), a single dose of TXA followed by 1.0 g three and nine hours postoperatively (group C), or a single dose of TXA followed by 1.0 g orally three, nine, and 15 hours postoperatively (group D). All patients followed a routine enhanced-recovery protocol. The primary outcome measure was the total blood loss. Secondary outcome measures were hidden blood loss (HBL), reduction in the level of haemoglobin, the rate of transfusion and adverse events. Results. Groups C (661.1 ml, . sd. 262.4) and D (597.7 ml, . sd. 219.6) had significantly lower mean total blood loss compared with groups A and B. The mean HBL was significantly lower in groups B (699.2 ml), C (533.1 ml) and D (469.9 ml) than in group A (p = 0.006, p < 0.001, and p < 0.001, respectively). Groups C (2.22 ml, . sd. 0.91) and D (2.04 ml, . sd. 0.95) had a lower reduction in the level of haemoglobin than groups A and B. However, there were no differences between groups C and D in relation to the three parameters. Conclusion. The addition of two or three postoperative doses of TXA to one preoperative dose produced a significant reduction in blood loss. The two-dose postoperative regimen is the least necessary regimen for clinical efficacy in primary unilateral TKA. The three-dose regimen produced maximum reduction of blood loss. Cite this article: Bone Joint J 2018;100-B:1025–32

Aims. In total knee arthroplasty (TKA), blood loss continues internally after surgery is complete. Typically, the total loss over 48 postoperative hours can be around 1,300 ml, with most occurring within the first 24 hours. We hypothesize that the full potential of tranexamic acid (TXA) to decrease TKA blood loss has not yet been harnessed because it is rarely used beyond the intraoperative period, and is usually withheld from ‘high-risk’ patients with a history of thromboembolic, cardiovascular, or cerebrovascular disease, a patient group who would benefit greatly from a reduced blood loss. Methods. TRAC-24 was a prospective, phase IV, single-centre, open label, parallel group, randomized controlled trial on patients undergoing TKA, including those labelled as high-risk. The primary outcome was indirect calculated blood loss (IBL) at 48 hours. Group 1 received 1 g intravenous (IV) TXA at the time of surgery and an additional 24-hour postoperative oral regime of four 1 g doses, while Group 2 only received the intraoperative dose and Group 3 did not receive any TXA. Results. Between July 2016 and July 2018, 552 patients were randomized to either Group 1 (n = 241), Group 2 (n = 243), or Group 3 (n = 68), and 551 were included in the final analysis. The blood loss did differ significantly between the two intervention groups (733.5 ml (SD 384.0) for Group 1 and 859.2 ml (SD 363.6 ml) for Group 2; mean difference -125.8 ml (95% confidence interval -194.0 to -57.5; p < 0.001). No differences in mortality or thromboembolic events were observed in any group. Conclusion. These data support the hypothesis that in TKA, a TXA regime consisting of IV 1 g perioperatively and four oral 1 g doses over 24 hours postoperatively significantly reduces blood loss beyond that achieved with a single IV 1 g perioperative dose alone. TXA appears safe in patients with history of thromboembolic, cardiovascular, and cerebrovascular disease. Cite this article: Bone Joint J 2021;103-B(10):1595–1603

We studied 99 patients who were undergoing total knee arthroplasty (TKA) to determine the optimum protocol for the administration of tranexamic acid (TNA) in order to reduce blood loss. It decreased by more than 40% after the administration of TNA. The haemostatic effect was greatest when TNA was given preoperatively and on deflation of the tourniquet. There was no increase in the incidence of adverse affects in the patients receiving TNA, compared with a control group. We conclude that two injections of TNA, one given preoperatively and one on deflation of the tourniquet, significantly reduce blood loss without increasing the risk of thromboembolic complications

We conducted a systematic review and meta-analysis of randomised controlled trials evaluating the effect of tranexamic acid (TXA) upon blood loss and transfusion in primary total knee replacement. The review used the generic evaluation tool designed by the Cochrane Bone, Joint and Muscle Trauma Group. A total of 19 trials were eligible: 18 used intravenous administration, one also evaluated oral dosing and one trial evaluated topical use. TXA led to a significant reduction in the proportion of patients requiring blood transfusion (risk ratio (RR) 2.56, 95% confidence interval (CI) 2.1 to 3.1, p < 0.001; heterogeneity I² = 75%; 14 trials, 824 patients). Using TXA also reduced total blood loss by a mean of 591 ml (95% CI 536 to 647, p < 0.001; I² = 78%; nine trials, 763 patients). The clinical interpretation of these findings is limited by substantial heterogeneity. However, subgroup analysis of high-dose (> 4 g) TXA showed a plausible consistent reduction in blood transfusion requirements (RR 5.33; 95% CI 2.44 to 11.65, p < 0.001; I² = 0%), a finding that should be confirmed by a further well-designed trial. The current evidence from trials does not support an increased risk of deep-vein thrombosis (13 trials, 801 patients) or pulmonary embolism (18 trials, 971 patients) due to TXA administration.

Aims. The aim of this study was to examine whether tourniquet use can improve perioperative blood loss, early function recovery, and pain after primary total knee arthroplasty (TKA) in the setting of multiple-dose intravenous tranexamic acid. Methods. This was a prospective, randomized clinical trial including 180 patients undergoing TKA with multiple doses of intravenous tranexamic acid. One group was treated with a tourniquet during the entire procedure, the second group received a tourniquet during cementing, and the third group did not receive a tourniquet. All patients received the same protocol of intravenous tranexamic acid (20 mg/kg) before skin incision, and three and six hours later (10 mg/kg). The primary outcome measure was perioperative blood loss. Secondary outcome measures were creatine kinase (CK), CRP, interleukin-6 (IL-6), visual analogue scale (VAS) pain score, limb swelling ratio, quadriceps strength, straight leg raising, range of motion (ROM), American Knee Society Score (KSS), and adverse events. Results. The mean total blood loss was lowest in the no-tourniquet group at 867.32 ml (SD 201.11), increased in the limited-tourniquet group at 1024.35 ml (SD 176.35), and was highest in the tourniquet group at 1,213.00 ml (SD 211.48). The hidden blood loss was lowest in the no-tourniquet group (both p < 0.001). There was less mean intraoperative blood loss in the tourniquet group (77.48 ml (SD 24.82)) than in the limited-tourniquet group (137.04 ml (SD 26.96)) and the no-tourniquet group (212.99 ml (SD 56.35); both p < 0.001). Patients in the tourniquet group showed significantly higher levels of muscle damage and inflammation biomarkers such as CK, CRP, and IL-6 than the other two groups (p < 0.05). Outcomes for VAS pain scores, limb swelling ratio, quadriceps strength, straight leg raising, ROM, and KSS were significantly better in the no-tourniquet group at three weeks postoperatively (p < 0.05), but there were no significant differences at three months. No significant differences were observed among the three groups with respect to transfusion rate, thrombotic events, or the length of hospital stay. Conclusion. Patients who underwent TKA with multiple doses of intravenous tranexamic acid but without a tourniquet presented lower total blood loss and hidden blood loss, and they showed less postoperative inflammation reaction, less muscle damage, lower VAS pain score, and better early knee function. Our results argue for not using a tourniquet during TKA. Cite this article: Bone Joint Res 2020;9(6):322–332

We have investigated the effect of using tranexamic acid (TXA) during peri-acetabular osteotomy (PAO) on peri-operative blood loss and blood transfusion requirements. In addition we analysed whether the use of TXA was associated with an increased risk of venous thromboembolism (VTE) following this procedure.

A consecutive series of 96 PAOs, performed by a single surgeon, were reviewed. A total of 48 patients received TXA and 48 did not. The TXA group received a continuous infusion of TXA at a rate of 10 mg/kg/h. The primary outcome measure was the requirement for blood transfusion. Secondary outcomes included total blood loss, the decrease in the level of haemoglobin in the blood, the length of hospital stay, and the complications of this treatment.

The mean rate of transfusion was significantly lower in the TXA group (62.5% vs 12.5%, p < 0.001). The mean blood loss was also significantly reduced in the TXA group (1.9 L (standard deviation (sd) 0.9) vs 1.5 L (sd 0.7), p < 0.01). No post-operative episodes of VTE were identified in either group.

The use of TXA reduced the blood loss and the rate of transfusion after PAO significantly, without adverse effects such as an increased rate of VTE.

Cite this article: Bone Joint J 2015;97-B:1604–7.

Aims. The purpose of the present study was to evaluate the impact of intravenous tranexamic acid on the reduction of blood loss, transfusion rate, and early post-operative clinical outcome in total shoulder arthroplasty. Patients and Methods. A randomised, placebo-controlled trial which included 54 patients undergoing unilateral primary stemless anatomical or stemmed reverse total shoulder arthroplasty was undertaken. Patients received either 100 ml saline (placebo, n = 27), or 100 ml saline together with 1000 mg of tranexamic acid (TXA, n = 27) intravenously prior to skin incision and during wound closure. Peri-operative blood loss via an intra-articular drain was recorded and total blood loss was calculated. The post-operative transfusion rate was documented. Assessment of early clinical parameters included the visual analogue scale for pain (VAS), documentation of haematoma formation and adverse events. Results. Mean peri-operative blood drainage (placebo: 170 ml versus TXA: 50 ml, p = 0.001) and calculated mean total blood loss (placebo: 1248.2 ml versus TXA: 871.0 ml, p = 0.009) were significantly lower in the TXA group. No transfusions were necessary during the study period in either group. Mean VAS for pain significantly decreased from pre-operative (VAS 7) to the early post-operative period (VAS 1.7, p < 0.001). Significant differences regarding mean post-operative pain between placebo (VAS 2.0) and TXA (VAS 1.3) were detected (p = 0.05). The occurrence of haematomas was significantly more frequent in the placebo (59.3%, n = 16) than in the TXA group (25.9%, n = 6, p = 0.027). Whereas only mild haematomas developed in the TXA group, in the placebo group a total of 22.2% (n = 6) developed either moderate or severe haematomas. No adverse events associated with administration of TXA occurred. Conclusion. Intravenous administration of TXA successfully reduced mean peri-operative blood drainage, total estimated blood loss, pain during the first post-operative days, and haematoma formation in total shoulder arthroplasty. Cite this article: Bone Joint J 2017;99-B:1073–9

In our department we use an enhanced recovery protocol for joint replacement of the lower limb. This incorporates the use of intravenous tranexamic acid (IVTA; 15 mg/kg) at the induction of anaesthesia. Recently there was a national shortage of IVTA for 18 weeks; during this period all patients received an oral preparation of tranexamic acid (OTA; 25 mg/kg). This retrospective study compares the safety (surgical and medical complications) and efficacy (reduction of transfusion requirements) of OTA and IVTA. During the study period a total of 2698 patients received IVTA and 302 received OTA. After adjusting for a range of patient and surgical factors, the odds ratio (OR) of receiving a blood transfusion was significantly higher with IVTA than with OTA (OR 0.48 (95% confidence interval 0.26 to 0.89), p = 0.019), whereas the safety profile was similar, based on length of stay, rate of readmission, return to theatre, deep infection, stroke, gastrointestinal bleeding, myocardial infarction, pneumonia, deep-vein thrombosis and pulmonary embolism. The financial benefit of OTA is £2.04 for a 70 kg patient; this is amplified when the cost saving associated with significantly fewer blood transfusions is considered. Although the number of patients in the study is modest, this work supports the use of OTA, and we recommend that a randomised trial be undertaken to compare the different methods of administering tranexamic acid. Cite this article: Bone Joint J 2013;95-B:1556–61

Aims. The aim of this study was to examine the efficacy and safety of multiple boluses of intravenous (IV) tranexamic acid (TXA) on the hidden blood loss (HBL) and inflammatory response following primary total hip arthroplasty (THA). Patients and Methods. A total of 150 patients were allocated randomly to receive a single bolus of 20 mg/kg IV TXA before the incision (group A), a single bolus followed by a second bolus of 1 g IV-TXA three hours later (group B) or a single bolus followed by two boluses of 1 g IV-TXA three and six hours later (group C). All patients were treated using a standard peri-operative enhanced recovery protocol. Primary outcomes were HBL and the level of haemoglobin (Hb) as well as the levels of C-reactive protein (CRP) and interleukin-6 (IL-6) as markers of inflammation. Secondary outcomes included the length of stay in hospital and the incidence of venous thromboembolism (VTE). Results. The mean HBL was significantly lower in group C (402.13 ml standard deviation (. sd). 225.97) than group A (679.28 ml. sd. 277.16, p < 0.001) or B (560.62 ml . sd. 295.22, p = 0.010). The decrease in the level of Hb between the pre-operative baseline and the level on the third post-operative day was 30.82 g/L (. sd. 6.31 g/L) in group A, 27.16 g/L (. sd. 6.83) in group B and 21.98 g/L (. sd. 3.72) in group C. This decrease differed significantly among the three groups (p < 0.01). The mean level of CRP was significantly lower in group C than in the other two groups on the second (p ≤ 0.034) and third post-operative days (p ≤ 0.014). The levels of IL-6 were significantly lower in group C than group A on the first three post-operative days (p = 0.023). The mean length of stay was significantly lower in group C than group A (p = 0.023). No VTE or other adverse events occurred. Conclusion. Multiple boluses of IV-TXA can effectively reduce HBL following primary THA. A regime of three boluses leads to a smaller decrease in the level of Hb, less post-operative inflammation and a shorter length of stay in hospital than a single bolus. Cite this article: Bone Joint J 2017;99-B:1442–9

Tranexamic acid (TEA), an inhibitor of fibrinolysis, reduces blood loss after routine total knee replacement (TKR). However, controversy persists regarding the dosage and timing of administration of this drug during surgery. We performed a prospective randomised controlled study to examine the optimum blood-saving effect of TEA in minimally invasive TKR. We randomly assigned 151 patients who underwent unilateral minimally invasive TKR to three groups: 1) a placebo group (50 patients); 2) a one-dose TEA group (52 patients), who received one injection of TEA (10 mg/kg) intra-operatively on deflation of the tourniquet; and 3) a two-dose TEA group (49 patients), who received two injections of TEA (10 mg/kg) given pre-operatively and intra-operatively. Total blood loss was calculated from the maximum loss of haemoglobin. All patients were followed clinically for the presence of venous thromboembolism (VTE). The mean total blood loss was significantly higher in the placebo group than in the other two groups (1222 ml (845 to 2043) versus 1035 ml (397 to 1934) and 986 ml (542 to 1811), respectively (both p < 0.0001)). The mean blood loss was not significantly different between the one- and two-TEA groups (p = 0.148). The mean transfusion rate was higher in the placebo group than in the other two groups (22% versus 3.8% (p = 0.006) and 6.1% (p = 0.041), respectively) and there was no statistically significant difference in the mean transfusion rate between the one- and two-TEA groups (p = 0.672). Only one patient, in the two-dose group, had a radiologically confirmed deep venous thrombosis. Our prospective randomised controlled study showed that one intra-operative injection of TEA is effective for blood conservation after minimally invasive TKR

Aims. Blood transfusion and postoperative anaemia are complications of total knee arthroplasty (TKA) that are associated with substantial healthcare costs, morbidity, and mortality. There are few data from large datasets on the risk factors for these complications. Methods. We retrospectively reviewed the records of TKA patients from a single tertiary care institution from February 2016 to December 2020. There were a total of 14,901 patients in this cohort with a mean age of 67.9 years (SD 9.2), and 5,575 patients (37.4%) were male. Outcomes included perioperative blood transfusion and postoperative anaemia, defined a priori as haemoglobin level < 10 g/dl measured on the first day postoperatively. In order to establish a preoperative haemoglobin cutoff, we investigated a preoperative haemoglobin level that would limit transfusion likelihood to ≤ 1% (13 g/dl) and postoperative anaemia likelihood to 4.1%. Risk factors were assessed through multivariable Poisson regression modelling with robust error variance. Results. In multivariable analyses, each gram of tranexamic acid reduced transfusion likelihood by 39% (adjusted risk ratio (ARR) 0.61 (95% confidence interval (CI) 0.47 to 0.78)). Risk factors associated with an increased risk of transfusion included operating time (ARR 2.07 (95% CI 1.54 to 2.77)) and drain use (ARR 1.73 (95% CI 1.34 to 2.24)). Conclusion. In this study, we found that increased tranexamic acid dosing, decreased operating time, and decreased drain use may reduce transfusions following TKA. We also established a single preoperative haemoglobin cutoff of 13 g/dl that could help minimize transfusions and reduce postoperative complete blood counts. Cite this article: Bone Joint J 2023;105-B(10):1086–1093

The February 2023 Foot & Ankle Roundup. 360. looks at: Joint inflammatory response in ankle and pilon fractures; Tibiotalocalcaneal fusion with a custom cage; Topical application of tranexamic acid can reduce blood loss in calcaneal fractures; Risk factors for failure of total ankle arthroplasty; Pain catastrophizing: the same as pain forecasting?

The February 2024 Research Roundup. 360. looks at: If you use a surgical helmet, you should seal your gown-glove interface; The use of iodophor-impregnated drapes in patients with iodine-related allergies: a case series and review of the literature; Location of the ovaries in children and efficacy of gonadal shielding in hip and pelvis radiography; Prehospital tranexamic acid administration does not improve outcomes in severe trauma patients; Silver-coated distal femur megaprosthesis in chronic infections with severe bone loss: a multicentre case series