The antifibrinolytic and anti-inflammatory effects of a high initial-dose tranexamic acid in total knee arthroplasty: a randomized controlled trial
Lei YT, Xie JW, Huang Q, Huang W, Pei FX
International orthopaedics. 2019
PURPOSE The aim of this study was to evaluate the effects of a high initial-dose (60 mg/kg) intravenous tranexamic acid (IV-TXA) on fibrinolysis and inflammation after total knee arthroplasty (TKA). METHODS A total of 132 patients were categorized into two groups based on different TXA regimens: 20 mg/kg before incision (A) or 60 mg/kg before incision (B). All patients received five doses of 1 g TXA at three, six, 12, 18, and 24 hours after the first dose. The primary outcomes were peri-operative blood loss and transfusion rate. Other outcome measurements such as, haemoglobin level, fibrinolysis parameters [fibrin(-ogen) degradation products (FDP), D-dimer], inflammatory factors [C-reactive protein (CRP), interleukin-6 (IL-6)], visual analog scale (VAS) score, consumption of analgesic rescue, coagulation parameters [activated partial thromboplastin time (APTT), prothrombin time (PT), platelet count, thrombelastography (TEG), and anti-factor Xa activity (AFXa)] and complications, were also compared. RESULTS There was a favourable effect in reducing peri-operative blood loss and transfusion rate for patients in Group B, compared with patients in Group A. In addition, the levels of FDP, D-dimer, CRP, IL-6, and dynamic pain in Group B were significantly lower than those in Group A on post-operative days one, two and three. There were no statistically significant differences in postoperative coagulation parameters and complications between the two groups. CONCLUSION A high initial-dose (60 mg/kg) IV-TXA before surgery followed by five doses can further reduce blood loss, provide additional fibrinolysis and inflammation control, and ameliorate post-operative pain following TKA, without increasing the risk of treatment-related complications.
Finding the Optimal Regimen for Oral Tranexamic Acid Administration in Primary Total Hip Arthroplasty: A Randomized Controlled Trial
Wang D, Wang HY, Luo ZY, Pei FX, Zhou ZK, Zeng WN
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.
Effect of Multiple Doses of Oral Tranexamic Acid on Haemostasis and Inflammatory Reaction in Total Hip Arthroplasty: A Randomized Controlled Trial
Wang D, Yang Y, He C, Luo ZY, Pei FX, Li Q, Zhou ZK, Zeng WN
Thrombosis and haemostasis. 2019;119(1):92-103
Tranexamic acid (TXA) reduces surgical blood loss and alleviates inflammatory response in total hip arthroplasty. However, studies have not identified an optimal regimen. The objective of this study was to identify the most effective regimen of multiple-dose oral TXA in achieving maximum reduction of blood loss and inflammatory response based on pharmacokinetic recommendations. We prospectively studied four multiple-dose regimens (60 patients each) with control group (group A: matching placebo). The four multiple-dose regimens included: 2-g oral TXA 2 hours pre-operatively followed by 1-g oral TXA 3 hours post-operatively (group B), 2-g oral TXA followed by 1-g oral TXA 3 and 7 hours post-operatively (group C), 2-g oral TXA followed by 1-g oral TXA 3, 7 and 11 hours post-operatively (group D) and 2-g oral TXA followed by 1-g oral TXA 3, 7, 11 and 15 hours post-operatively (group E). The primary endpoint was estimated blood loss on post-operative day (POD) 3. Secondary endpoints were thromboelastographic parameters, inflammatory components, function recovery and adverse events. Groups D and E had significantly less blood loss on POD 3, with no significant difference between the two groups. Group E had the most prolonged haemostatic effect, and all thromboelastographic parameters remained within normal ranges. Group E had the lowest levels of inflammatory cytokines and the greatest range of motion. No thromboembolic complications were observed. The post-operative four-dose regimen brings about maximum efficacy in reducing blood loss, alleviating inflammatory response and improving analgaesia and immediate recovery.
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
Wang HY, Wang L, Luo ZY, Wang D, Tang X, Zhou ZK, Pei FX
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 ).
Tranexamic acid in primary total knee arthroplasty without tourniquet: a randomized, controlled trial of oral versus intravenous versus topical administration
Wang D, Wang HY, Cao C, Li LL, Meng WK, Pei FX, Li DH, Zhou ZK, Zeng WN
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.
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
Wang D, Wang HY, Luo ZY, Meng WK, Pei FX, Li Q, Zhou ZK, Zeng WN
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.
The antifibrinolytic and anti-inflammatory effects of multiple doses of oral tranexamic acid in total knee arthroplasty patients: a randomized controlled trial
Wang D, Luo ZY, Yu ZP, Liu LX, Chen C, Meng WK, Yu QP, Pei FX, Zhou ZK, Zeng WN
Journal of Thrombosis and Haemostasis. 2018;16((12):):2442-2453.
Essentials Perioperative blood loss and inflammatory response can significantly affect recovery after surgery. We studied the effects of multiple-dose oral tranexamic acid on blood loss and inflammatory response. A postoperative four-dose regimen brought about maximum reduction in postoperative blood loss. A postoperative four-dose regimen reduced inflammatory response and promoted early rehabilitation. SUMMARY Background Tranexamic acid (TXA) can reduce blood loss and the inflammatory response at multiple doses in total knee arthroplasty patients. However, the optimal regimen has not been determined. Objectives To identify the most effective regimen for achieving maximum reductions in blood loss and the inflammatory response. Patients/Methods Two hundred and seventy-five patients were randomized to receive a placebo (group A), a single 2-g oral dose of TXA 2 h preoperatively followed by 1 g of oral TXA 3 h postoperatively (group B), a single dose followed by 1 g of oral TXA 3 h and 7 h postoperatively (group C), a single dose followed by 1 g of oral TXA 3 h, 7 h and 11 h postoperatively (group D), or a single dose followed by 1 g of oral TXA 3 h, 7 h, 11 h and 15 h postoperatively (group E). The primary outcome was total blood loss on postoperative day (POD) 3. Secondary outcomes included a decrease in the hemoglobin level, coagulation parameters, inflammatory marker levels, and thromboembolic complications. Results Groups D and E had significantly lower blood loss and smaller decreases in hemoglobin level than groups A, B, and C, with no significant difference on POD 3 between groups D and E. Significantly enhanced coagulation was identified for the four multiple-dose regimens; however, all thromboelastographic parameters remained within normal ranges. Group E had the lowest inflammatory marker levels and pain, and the greatest range of motion. No thromboembolic complications were identified. Conclusion The four-dose regimen yielded the maximum reductions in blood loss and inflammatory response, improved analgesia, and promoted early rehabilitation. Further studies are required to ensure that these findings are reproducible.
Oral vs intravenous vs topical tranexamic acid in primary hip arthroplasty: a prospective, randomized, double-blind, controlled study
Luo ZY, Wang HY, Wang D, Zhou K, Pei FX, Zhou ZK
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.
Intravenous combined with topical administration of tranexamic acid in primary total hip arthroplasty: a randomized controlled trial
Zeng Y, Si HB, Shen B, Yang J, Zhou ZK, Kang PD, Pei FX
Orthopaedic Surgery. 2017;9((2):):174-179
OBJECTIVE Although there are still some controversies, large previous studies have confirmed that intravenous (i.v.) tranexamic acid (TXA) can effectively reduce blood loss and transfusions in total hip arthroplasty (THA) without increasing the risk of deep venous thrombosis. However, few studies have investigated the combination of i.v. and topical application of TXA in primary THA. The purpose of our current study is to examine whether i.v. combined with topical administration of TXA decreases postoperative blood loss and transfusion rates after THA. METHODS From December 2013 to May 2014, all adult patients undergoing primary THA at our arthroplasty center were considered for inclusion in the present study. Included patients were randomly assigned to two groups by computer-generated list number: a TXA group and a placebo group. Patients in the TXA group received i.v. (15 mg/kg) combined with topical administration (1.0 g) of TXA during the THA procedure, and patients in the other group received the same dosage of normal saline both i.v. and topically. Our primary outcome measures were total blood loss (calculated using Gross's equation), hemoglobin, hematocrit and platelet concentration changes on the third postoperative day, the amount of drainage, the amount of intraoperative blood loss, the frequency of transfusion, and the number of blood units transfused. Secondary outcome measures were the length of postoperative stay, range of hip motion (measured by goniometer), Harris hip scores (HHS), and any perioperative complications or events such as infection, DVT or PE. Range of motion and HHS were measured at 3 week follow-up and compared with preoperative values. RESULTS This trial included 100 patients (50 in each group). Patients in the TXA group had significantly higher postoperative hemoglobin (103 vs 87.7 g/dL, P < 0.01), lower hemoglobin changes (32.2 vs 44.9 g/dL, P < 0.01), higher postoperative hematocrit (0.32 vs 0.27 L/L, P < 0.01), lower hematocrit changes (0.1 vs 0.14 L/L, P < 0.01), lower total blood loss (822 vs 1100 mL, P = 0.004), lower drainage (117.8 vs 242.4 mL, P < 0.01), lower intraoperative blood loss (193.8 vs 288.2 mL, P < 0.01), and lower transfusion rate (2% vs 34%, P < 0.01) compared with those in the placebo group. No statistical difference was found in postoperative platelets between the two groups. There were no differences in perioperative complications or venous thromboembolism (VTE) events. CONCLUSIONS The combined administration of i.v. and topical TXA resulted in a clinically relevant reduction in blood loss, compared with placebo group. No thromboembolic complications were observed. This randomized controlled trial supports the combined i.v. and topical administration of TXA in primary THA.
The efficacy and safety of postoperative retransfusion drain following total hip arthroplasty: a meta-analysis
Xie JW, Xu B, Kang PD, Zhou ZK, Shen B, Yang J, Pei FX
Zhonghua Wai Ke Za Zhi [Chinese Journal of Surgery]. 2016;54((2)):108-13.
OBJECTIVE To investigate the effectiveness and safety of post-operative retransfusion drain(PRD) after total hip arthroplasty. METHODS A systematic literature review based on PubMed, EMBase, the Cochrane Library, China Biology Medicine disc, CNKI, VIP and WanFang Database in any language regarding PRD following total hip arthroplasty was performed.The data was evaluated using modified Jadad score and then analyzed using RevMan 5.2. RESULTS Nine randomized controlled trials totaling 1 824 patients, 913 patients in PRD group and 911 in control group, were eligible for data extraction and Meta-analysis.The results indicated that the use of PRD could reduce the requirement of allogeneic blood transfusion when compared with ordinary vacuum drainage (RR=0.61, 95% CI= 0.47-0.79), but the benefit was not found when compared with no drainage group(RR=1.07, 95% CI=0.67-1.71). And the postoperative hemoglobin level was higher in PRD group(MD=0.14, 95% CI=0.01-0.27, P=0.04). No significant difference was identified regarding transfusion index, length of hospital stay, the incidence of febrile reaction and wound-related complications. CONCLUSIONS PRD in reducing requirement of blood transfusion following THA is effective and safe when compared with ordinary vacuum drainage, but the benefit is not found when compared with no drainage.And more robust evidence is needed to confirm this result.