J Knee Surg 2018; 31(07): 654-663
DOI: 10.1055/s-0037-1606376
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Most Effective Regimen of Tranexamic Acid for Reducing Bleeding and Transfusions in Primary Total Knee Arthroplasty: A Meta-Analysis of Randomized Controlled Trials

Wen-Li Dai
1   Department of Orthopaedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
,
Ai-Guo Zhou
1   Department of Orthopaedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
,
Hua Zhang
1   Department of Orthopaedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
,
Jian Zhang
1   Department of Orthopaedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
› Author Affiliations
Further Information

Publication History

24 January 2017

04 August 2017

Publication Date:
11 September 2017 (online)

Abstract

The use of tranexamic acid (TXA) during primary total knee arthroplasty (TKA) is well documented. However, considering the potential side effects, including deep vein thrombosis (DVT) and pulmonary embolism (PE), the ideal route of administration remains controversial. Therefore, we performed a meta-analysis to compare the efficacy of topical versus intravenous TXA and explore the most effective regimen in patients undergoing primary TKA. We conducted a systematic literature search in PubMed, Embase, and the Cochrane database through July 2016 to identify randomized controlled trials (RCTs) evaluating the efficacy and safety of topical and intravenous TXA in primary TKA. We assessed the risk of bias using the Cochrane Collaboration's tool. We assessed the quality of evidence using the GRADE profiler software. A total of 15 RCTs including 1,240 participants met the inclusion criteria. We found no statistically significant difference between topical and intravenous TXA in terms of transfusion rate (p = 0.75), total blood loss (p = 0.51), total drain output (p = 0.60), maximum hemoglobin drop (p = 0.24), length of stay (p = 0.08), and thromboembolic complications (p = 0.73). Subgroup analyses showed that compared with 1 g topical TXA, 2 g topical TXA was more effective to reduce blood transfusion rate and total blood loss, and did not increase thromboembolic complications. We also found three times intravenous TXA was more effective than one time of intravenous TXA to reduce blood transfusion rate and total blood loss without increasing of thromboembolic complications. Topical TXA had a similar efficacy to intravenous TXA in reducing blood transfusion and blood loss, and did not increase the risk of thromboembolic complications in primary TKA. Besides, the current meta-analysis suggested that three times of intravenous TXA is efficient and safe. We also recommended 2 g topical TXA instead of 1 g topical TXA because it was more efficient to reduce blood transfusion rate and total blood loss and did not increase thromboembolic complications.

Authors' Contributions

W.L.D. conceived the study, participated in the design, collected data, performed statistical analyses, and drafted the article. A.G.Z. collected data and assisted with statistical analyses. H.Z. collected and interpreted data, drafted the article. J.Z. conceived the study, participated in the design, and helped draft the article. All the authors have read and approved the final article.


 
  • References

  • 1 Carr AJ, Robertsson O, Graves S. , et al. Knee replacement. Lancet 2012; 379 (9823): 1331-1340
  • 2 Lotke PA, Faralli VJ, Orenstein EM, Ecker ML. Blood loss after total knee replacement. Effects of tourniquet release and continuous passive motion. J Bone Joint Surg Am 1991; 73 (07) 1037-1040
  • 3 Sehat KR, Evans R, Newman JH. How much blood is really lost in total knee arthroplasty? Correct blood loss management should take hidden loss into account. Knee 2000; 7 (03) 151-155
  • 4 Cushner FD, Friedman RJ. Blood loss in total knee arthroplasty. Clin Orthop Relat Res 1991; (269) 98-101
  • 5 Friedman R, Homering M, Holberg G, Berkowitz SD. Allogeneic blood transfusions and postoperative infections after total hip or knee arthroplasty. J Bone Joint Surg Am 2014; 96 (04) 272-278
  • 6 Stokes ME, Ye X, Shah M. , et al. Impact of bleeding-related complications and/or blood product transfusions on hospital costs in inpatient surgical patients. BMC Health Serv Res 2011; 11: 135
  • 7 Lemaire R. Strategies for blood management in orthopaedic and trauma surgery. J Bone Joint Surg Br 2008; 90 (09) 1128-1136
  • 8 Dunn CJ, Goa KL. Tranexamic acid: a review of its use in surgery and other indications. Drugs 1999; 57 (06) 1005-1032
  • 9 Ker K, Edwards P, Perel P, Shakur H, Roberts I. Effect of tranexamic acid on surgical bleeding: systematic review and cumulative meta-analysis. BMJ 2012; 344: e3054
  • 10 Yang ZG, Chen WP, Wu LD. Effectiveness and safety of tranexamic acid in reducing blood loss in total knee arthroplasty: a meta-analysis. J Bone Joint Surg Am 2012; 94 (13) 1153-1159
  • 11 Alshryda S, Sarda P, Sukeik M, Nargol A, Blenkinsopp J, Mason JM. Tranexamic acid in total knee replacement: a systematic review and meta-analysis. J Bone Joint Surg Br 2011; 93 (12) 1577-1585
  • 12 Zhang H, Chen J, Chen F, Que W. The effect of tranexamic acid on blood loss and use of blood products in total knee arthroplasty: a meta-analysis. Knee Surg Sports Traumatol Arthrosc 2012; 20 (09) 1742-1752
  • 13 Raveendran R, Wong J. Tranexamic acid reduces blood transfusion in surgical patients while its effects on thromboembolic events and mortality are uncertain. Evid Based Med 2013; 18 (02) 65-66
  • 14 Wong J, Abrishami A, El Beheiry H. , et al. Topical application of tranexamic acid reduces postoperative blood loss in total knee arthroplasty: a randomized, controlled trial. J Bone Joint Surg Am 2010; 92 (15) 2503-2513
  • 15 Shemshaki H, Nourian SM, Nourian N, Dehghani M, Mokhtari M, Mazoochian F. One step closer to sparing total blood loss and transfusion rate in total knee arthroplasty: a meta-analysis of different methods of tranexamic acid administration. Arch Orthop Trauma Surg 2015; 135 (04) 573-588
  • 16 Gomez-Barrena E, Ortega-Andreu M, Padilla-Eguiluz NG, Pérez-Chrzanowska H, Figueredo-Zalve R. Topical intra-articular compared with intravenous tranexamic acid to reduce blood loss in primary total knee replacement: a double-blind, randomized, controlled, noninferiority clinical trial. J Bone Joint Surg Am 2014; 96 (23) 1937-1944
  • 17 Tzatzairis TK, Drosos GI, Kotsios SE, Ververidis AN, Vogiatzaki TD, Kazakos KI. Intravenous vs Topical Tranexamic Acid in Total Knee Arthroplasty Without Tourniquet Application: A Randomized Controlled Study. J Arthroplasty 2016; 31 (11) 2465-2470
  • 18 Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available at: http://handbook.cochrane.org . Accessed July 1, 2016
  • 19 Moher D, Liberati A, Tetzlaff J, Altman DG. ; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 2009; 339: b2535
  • 20 Langer G, Meerpohl JJ, Perleth M, Gartlehner G, Kaminski-Hartenthaler A, Schünemann H. GRADE guidelines: 2. Framing the question and deciding on important outcomes [in German]. Z Evid Fortbild Qual Gesundhwes 2012; 106 (05) 369-376
  • 21 Guyatt GH, Oxman AD, Schünemann HJ, Tugwell P, Knottnerus A. GRADE guidelines: a new series of articles in the Journal of Clinical Epidemiology. J Clin Epidemiol 2011; 64 (04) 380-382
  • 22 Meerpohl JJ, Langer G, Perleth M, Gartlehner G, Kaminski-Hartenthaler A, Schünemann H. GRADE guidelines: 4. Rating the quality of evidence - limitations of clinical trials (risk of bias) [in German]. Z Evid Fortbild Qual Gesundhwes 2012; 106 (06) 457-469
  • 23 Perleth M, Langer G, Meerpohl JJ, Gartlehner G, Kaminski-Hartenthaler A, Schünemann HJ. GRADE guidelines: 7. Rating the quality of evidence – inconsistency [in German]. Z Evid Fortbild Qual Gesundhwes 2012; 106 (10) 733-744
  • 24 Rasch A, Perleth M, Langer G. , et al. GRADE guidelines: 8. Rating the quality of evidence – indirectness [in German]. Z Evid Fortbild Qual Gesundhwes 2012; 106 (10) 745-753
  • 25 Kulig M, Perleth M, Langer G. , et al. GRADE guidelines: 6. Rating the quality of evidence: imprecision [in German]. Z Evid Fortbild Qual Gesundhwes 2012; 106 (09) 677-688
  • 26 Nolting A, Perleth M, Langer G. , et al. GRADE guidelines: 5. Rating the quality of evidence: publication bias [in German]. Z Evid Fortbild Qual Gesundhwes 2012; 106 (09) 670-676
  • 27 Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003; 327 (7414): 557-560
  • 28 Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315 (7109): 629-634
  • 29 Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics 1994; 50 (04) 1088-1101
  • 30 Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics 1977; 33 (01) 159-174
  • 31 Sarzaeem MM, Razi M, Kazemian G, Moghaddam ME, Rasi AM, Karimi M. Comparing efficacy of three methods of tranexamic acid administration in reducing hemoglobin drop following total knee arthroplasty. J Arthroplasty 2014; 29 (08) 1521-1524
  • 32 Patel JN, Spanyer JM, Smith LS, Huang J, Yakkanti MR, Malkani AL. Comparison of intravenous versus topical tranexamic acid in total knee arthroplasty: a prospective randomized study. J Arthroplasty 2014; 29 (08) 1528-1531
  • 33 Seo JG, Moon YW, Park SH, Kim SM, Ko KR. The comparative efficacies of intra-articular and IV tranexamic acid for reducing blood loss during total knee arthroplasty. Knee Surg Sports Traumatol Arthrosc 2013; 21 (08) 1869-1874
  • 34 Soni A, Saini R, Gulati A, Paul R, Bhatty S, Rajoli SR. Comparison between intravenous and intra-articular regimens of tranexamic acid in reducing blood loss during total knee arthroplasty. J Arthroplasty 2014; 29 (08) 1525-1527
  • 35 Maniar RN, Kumar G, Singhi T, Nayak RM, Maniar PR. Most effective regimen of tranexamic acid in knee arthroplasty: a prospective randomized controlled study in 240 patients. Clin Orthop Relat Res 2012; 470 (09) 2605-2612
  • 36 Çavuşoğlu AT, Ayanoğlu T, Esen E, Atalar H, Turanlı S. Is intraarticular administration of tranexamic acid efficient and safe as systemic administration in total knee arthroplasty? Single center, randomized, controlled trial [in Turkish]. Eklem Hastalik Cerrahisi 2015; 26 (03) 164-167
  • 37 Digas G, Koutsogiannis I, Meletiadis G, Antonopoulou E, Karamoulas V, Bikos Ch. Intra-articular injection of tranexamic acid reduce blood loss in cemented total knee arthroplasty. Eur J Orthop Surg Traumatol 2015; 25 (07) 1181-1188
  • 38 Aguilera X, Martínez-Zapata MJ, Hinarejos P. , et al. Topical and intravenous tranexamic acid reduce blood loss compared to routine hemostasis in total knee arthroplasty: a multicenter, randomized, controlled trial. Arch Orthop Trauma Surg 2015; 135 (07) 1017-1025
  • 39 Chen JY, Chin PL, Moo IH. , et al. Intravenous versus intra-articular tranexamic acid in total knee arthroplasty: A double-blinded randomised controlled noninferiority trial. Knee 2016; 23 (01) 152-156
  • 40 Öztaş S, Öztürk A, Akalin Y. , et al. The effect of local and systemic application of tranexamic acid on the amount of blood loss and allogeneic blood transfusion after total knee replacement. Acta Orthop Belg 2015; 81 (04) 698-707
  • 41 Ugurlu M, Aksekili MA, Caglar C, Yüksel K, Şahin E, Akyol M. Effect of topical and intravenously applied tranexamic acid compared to control group on bleeding in primary unilateral total knee arthroplasty. J Knee Surg 201 2017; 30 (02) 152-157
  • 42 Drosos GI, Ververidis A, Valkanis C. , et al. A randomized comparative study of topical versus intravenous tranexamic acid administration in enhanced recovery after surgery (ERAS) total knee replacement. J Orthop 2016; 13 (03) 127-131
  • 43 May JH, Rieser GR, Williams CG, Markert RJ, Bauman RD, Lawless MW. The assessment of blood loss during total knee arthroplasty when comparing intravenous vs intracapsular administration of tranexamic acid. J Arthroplasty 2016; 31 (11) 2452-2457
  • 44 Panteli M, Papakostidis C, Dahabreh Z, Giannoudis PV. Topical tranexamic acid in total knee replacement: a systematic review and meta-analysis. Knee 2013; 20 (05) 300-309
  • 45 Xie J, Ma J, Yao H, Yue C, Pei F. Multiple boluses of intravenous tranexamic acid to reduce hidden blood loss after primary total knee arthroplasty without tourniquet: a randomized clinical trial. J Arthroplasty 2016; 31 (11) 2458-2464