Finding the Optimal Regimen for Oral Tranexamic Acid Administration in Primary Total Hip Arthroplasty: A Randomized Controlled Trial
The Journal of bone and joint surgery. American volume. 2019;101(5):438-445
BACKGROUND Previous studies have confirmed that, compared with intravenous and intra-articular formulations, oral tranexamic acid (TXA) provides equivalent reduction in blood loss, at a substantially reduced cost and greater ease of administration. However, the optimal oral dosage regimen to achieve maximum blood-loss reduction remains unclear. The aim of this study was to assess the efficacy of a regimen of multiple doses of oral TXA on blood loss in primary total hip arthroplasty. METHODS In this randomized controlled trial, 200 patients were randomized to 1 of 4 interventions. Group A received a single dose of 2.0 g of TXA orally at 2 hours preoperatively. In addition to this same preoperative dose, Group B received 1.0 g of TXA orally at 3 hours postoperatively, Group C received 1.0 g of TXA orally at 3 and 9 hours postoperatively, and Group D received 1.0 g of TXA orally at 3, 9, and 15 hours postoperatively. All patients received a 1.0-g topical dose of TXA. The primary outcome was total blood loss. Secondary outcomes included hemoglobin reduction, transfusion rate, thromboembolic complications, and adverse events. RESULTS The mean total blood loss (and standard deviation) was significantly less in Groups B, C, and D (792.2 +/- 293.0, 630.8 +/- 229.9, and 553.0 +/- 186.1 mL, respectively) than in Group A (983.6 +/- 286.7 mL) (p < 0.001). Moreover, Groups C and D had a lower mean reduction in hemoglobin than did Groups A and B. However, no differences were identified between Groups C and D for blood loss and hemoglobin reduction. Additionally, no differences were observed among the groups regarding thromboembolic complications and transfusions. CONCLUSIONS The multiple postoperative doses of oral TXA further reduced blood loss compared with a single preoperative bolus. The regimen of a preoperative dose and 3 postoperative doses of oral TXA produced maximum effective reduction of blood loss in total hip arthroplasty. LEVEL OF EVIDENCE Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.
Intravenous and subsequent long-term oral tranexamic acid in enhanced-recovery primary total knee arthroplasty without the application of a tourniquet: a randomized placebo-controlled trial
BMC musculoskeletal disorders. 2019;20(1):478
BACKGROUND To assess the efficacy and safety of intravenous and subsequent long-term oral tranexamic acid (TXA) following total knee arthroplasty (TKA) without a tourniquet. METHODS In this double-blinded trial, 118 patients undergoing primary TKA were randomized into two groups: the patients in group A received intravenous TXA at 20-mg/kg 10 min before the surgery and 3 h postoperatively, and then oral 1 g TXA from postoperative day (POD) 1 to POD 14, and the patients in group B received intravenous TXA at 20-mg/kg 10 min before surgery and 3 h postoperatively, and then oral 1 g placebo from postoperative day (POD) 1 to POD 14. The primary outcome was total blood loss. Secondary outcomes included ecchymosis area and morbidity, postoperative transfusion, postoperative laboratory values, postoperative knee function and length of hospital stay. Complications, and patient satisfaction were also recorded. RESULTS The mean total blood loss was lower in Group A than in Group B (671.7 ml vs 915.8 ml, P = 0.001). There was no significant difference in the transfusion rate between the two groups. Group A had a higher hemoglobin than Group B on POD 3 (106.0 g/L vs 99.7 g/L, P = 0.001). However, no significant difference was found for Hb or hematocrit on POD 1 or POD 14 between the two groups. Patients in Group A had less ecchymosis morbidity (7 vs 38, P = 0.001), smaller ecchymosis area (1.6 vs 3.0, P = 0.001) than Group B. The blood coagulation level as measured by fibrinolysis (D-Dimer) was lower in Group A than in Group B on POD 1 and POD 3 (4.6 mg/L vs. 8.4 mg/L, respectively, P = 0.001; 1.5 mg/L vs. 3.3 mg/L, respectively, P = 0.001). However, there was no significant difference on POD 14, and the fibrin degradation products showed the same trend. Patients in Group A had less swelling than those in Group B on POD 3 and POD 14. The circumference of the knee was 43.1 cm vs. 46.1 cm (POD 3, P = 0.001) and 41.4 cm vs. 44.9 cm (POD 14, P = 0.001) in Group A vs Group B, respectively. Nevertheless, the circumference of the knee in the two groups was similar on POD 1 and POD 3 M. No significant differences were identified in knee function, pain score, or hospital stay. No significant differences were identified in thromboembolic complications, infection, hematoma, wound healing and patients satisfaction between the two groups. CONCLUSION Intravenous and subsequent long-term oral TXA produced less blood loss and less swelling and ecchymosis compared with short-term TXA without increasing the risk of complications. TRIAL REGISTRATION The trial was registered in the Chinese Clinical Trial Registry ( ChiCTR-IPR-17012264 ).
Blood-conserving efficacy of multiple doses of oral tranexamic acid associated with an enhanced-recovery programme in primary total knee arthroplasty: a randomized controlled trial
Bone & Joint Journal. 2018;100 B.C.((8)):1025-1032.
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.
Tranexamic acid in primary total knee arthroplasty without tourniquet: a randomized, controlled trial of oral versus intravenous versus topical administration
Scientific Reports. 2018;8((1)):13579.
Abundant literature confirms that intravenous (IV) and intra-articular (IA) administration of tranexamic acid (TXA) reduces blood loss in total knee arthroplasty (TKA). Oral formulations of TXA exhibit profound cost-saving benefits. However, comparisons of the clinical efficacy among three different modalities of TXA administration have not been previously investigated in the setting of TKA with no closed suction drain and tourniquet. A total of 180 patients undergoing TKA were randomized to receive 2-g oral TXA 2 hours preoperatively, 20-mg/kg IV TXA 5 minutes prior to incision, or 2-g IA TXA. The primary outcome was 72-hour blood loss. Secondary outcomes were reductions in hemoglobin, the rate of transfusions, and adverse events. No significant differences were identified with regard to the mean 72-hour blood loss among the three groups (1003 mL in oral group, 1108 mL in IV group, and 1059 mL in IA group, respectively). Similarly, hemoglobin reduction was equivalent among the groups. Only one patient in IV group exhibited deep venous thrombosis. No difference was identified regarding transfusion rates. Oral TXA results in similar blood loss in TKA, with a profound cost-saving benefit, compared with the IA and IV formulations.
Is topical or intravenous tranexamic acid preferred in total hip arthroplasty? A randomized, controlled, noninferiority clinical trial
Plos One. 2018;13((10)):e0204551.
PURPOSE The present study aimed to confirm the efficacy and safety of topical and intravenous tranexamic acid (TXA) compared with that of topical placebo and to assess the noninferiority between the two application methods of TXA in patients undergoing unilateral primary total hip arthroplasty. METHODS Our randomized controlled trial investigated 170 patients with 1:1:1 allocation to two doses of 10-mg/kg intravenous TXA, 3-g topical TXA, and topical placebo of 60-ml physiological saline groups. The primary outcome, total blood loss, was calculated with Nadler and Gross formula. The secondary outcomes included allogeneic blood transfusion requirement, drain blood loss, decreased hemoglobin level. Noninferiority would be established when the upper limit 95% CI is lower than 250 ml of the noninferiority margin for the mean difference of total blood loss between topical and intravenous TXA. Thromboembolic complication incidence was considered as a safety outcome. RESULTS The total blood loss of patients administered intravenous (mean+/-standard deviation, 1125+/-514 ml) and topical TXA (1211+/-425 ml) was significantly reduced compared with that of those administered topical placebo (1464+/-556 ml) (p = 0.0012). Drain blood loss and hemoglobin level reduction in patients administered with TXA were also significantly lower than those in patients administered topical placebo. The mean difference of total blood loss between topical and intravenous TXA is 86 ml (95% CI, -88 to 260 ml). The complications were comparable between patients managed with TXA and patients with topical placebo. CONCLUSION The noninferiority of topical TXA to intravenous TXA can not be concluded. Considering no significant difference was found in all efficacy outcomes between the two administration methods. Any of the two TXA administration methods can be adopted for blood loss prevention in total hip arthroplasty.
Oral vs intravenous vs topical tranexamic acid in primary hip arthroplasty: a prospective, randomized, double-blind, controlled study
The Journal of Arthroplasty. 2017;33((3):):786-793
BACKGROUND Tranexamic acid (TXA) has demonstrated efficacy in reducing blood loss, reduction in hemoglobin, and blood transfusion requirements in primary total hip arthroplasty (THA). The optimal mode of TXA administration for patients undergoing primary THA is unclear. The purpose of this randomized controlled trial is to determine whether oral administration of TXA was superior to intravenous or topical routes in these patients. METHODS In this double-blinded, placebo-controlled trial, patients undergoing primary THA were randomized to oral (2 g TXA orally 2 hours preoperatively), intravenous (20 mg/kg intravenous TXA bolus 5 minutes before the incision), or topical (2 g TXA applied topically) TXA groups. The primary outcome was the reduction in hemoglobin. Secondary outcomes included blood loss, transfusion rate, cost of TXA (Chinese yuan ( yen); in 2017, yen1 = $0.147), and adverse events. RESULTS One hundred eighty patients were randomized into the 3 groups. Demographic characteristics were similar among the groups. The mean reduction in hemoglobin was similar among the oral, intravenous, and topical groups (3.48 +/- 1.32, 3.58 +/- 1.07, and 3.66 +/- 1.26 g/dL, respectively). Similarly, the mean total blood loss did not differ significantly among the 3 groups. The oral group incurred the lowest TXA cost ( yen480) compared with that in the intravenous ( yen3329.28) and topical ( yen3540) groups (P = .01). None of the patients sustained a deep venous thrombosis, pulmonary embolism, or an infection. CONCLUSION The blood-sparing efficacy of oral TXA is comparable to that of the intravenous and topical forms. Oral TXA is recommended because of its cost-benefit superiority and ease of administration.
Tranexamic acid and blood loss during and after cesarean section: a meta-analysis
Journal of Perinatology. 2015;35((10)):818-25.
OBJECTIVE A meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate whether tranexamic acid (TXA) could significantly reduce blood loss during and after cesarean section (CS) when compared with no TXA. STUDY DESIGN MEDLINE (PubMed), EMBASE, Cochrane Central Register of Controlled Trials and Web of Science were searched to identify RCTs that compared intravenous TXA with no TXA before CS for blood loss. The related data were extracted by two independent authors. The fixed or random-effect methods were used to combine data. RESULT Eleven RCTs were included in this analysis with a total of 1276 women in TXA group and 1255 in no TXA (control) group. Total blood loss during and after CS was significantly less in TXA group than in control group (mean difference (MD) -141.61ml, 95% confidence interval (CI) -207.09 to -76.14, P<0.01). There was a significant reduction in intraoperative and postpartum blood loss in TXA group as compared with control group (MD -143.36ml, 95% CI -220.38 to -66.35, P<0.01; and MD -38.20ml, 95% CI -59.27 to -17.12, P<0.01, respectively). Declines in hemoglobin and hematocrit values after CS were both significantly less in TXA group than in control group. The difference of postpartum hemorrhage rate was statistically significant between groups (risk ratio (RR) 0.57, 95% CI 0.37 to 0.89, P=0.01). The need for blood transfusion was significantly less in TXA group than control group (RR 0.23, 95% CI 0.10 to 0.57, P<0.01). CONCLUSION Our results demonstrate that TXA offers an advantage over no TXA in reducing blood loss during and after CS.