Vol 7, No 2 (2022)
Research paper
Published online: 2022-06-23

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Effectiveness and safety of tranexamic acid in total knee arthroplasty: a systematic review and meta-analysis

Jaroslaw Pecold1, Mahdi Al-Jeabory1, Michal Pruc1, Svitlana Doan2, Ihor Navolokin2, Serhii Znamerovskyi2, Lukasz Szarpak13
Disaster Emerg Med J 2022;7(2):114-123.

Abstract

INTRODUCTION: Major elective orthopedic surgery is often associated with blood loss, requiring the need for blood transfusion. A possible pharmacological option to reduce surgical blood loss in total arthroplasty is the use of tranexamic acid. The objective of the study was to undertake a meta-analysis investigating the effects of tranexamic acid on knee arthroplasty.
MATERIAL AND METHODS: The study was designed as a systematic review and meta-analysis. The PubMed, Central, Web of Science, and Scopus databases were searched up to March 23, 2022, to identify randomized controlled trials concerning tranexamic acid (TXA) administration during knee arthroplasty. Overall and stratified pooled odds ratios (ORs) or mean differences (MDs) with their 95% confidence intervals (Cis) were obtained.
RESULTS: Fifty-two articles were included. Pooled analysis showed that hemoglobin changes in TXA group was 3.4 ± 3.1, compared to 4.03 ± 2.62 for non-TXA group (MD = −1.30; 95% CI: –1.57 to –1.03; I2 = 99%; p<0.001). Total blood loss was reported in 31 trials and was statistically significantly lower in the TXA group compared to non-TXA (MD = –391.51; 95% CI: −454.29 to −328.73; p < 0.001). Intraoperative blood loss was lower when using TXA rather than non-TXA (MD = −32.10; 95% CI: −50.63 to −13.58; p < 0.001). 24-hours blood loss from the drain was also lower with TXA than with placebo (MD = −228.68; 95% CI: −293.31 to −164.05; p < 0.001). The above dependencies also applied to the intravenous as well as topical application of TXA. Blood transfusion was performed in 11.2% of patients from TXA group, compared to 34.3% of patients treated with placebo (OR = 0.16; 95% CI: 0.11 to 0.22; p < 0.001). Deep vein thrombosis (DVT) was observed in 4.6% of patients treated with TXA, compared to 5.8% of patients treated with placebo (OR = 0.81; 95% CI: 0.49 to 1.35; p = 0.42) and pulmonary embolism was 0.5% in TXA group and 1.4% in placebo group (OR = 0.44; 95% CI: 0.15 to 1.36; p = 0.15).
CONCLUSIONS: Tranexamic acid is effective and safe in reducing blood loss, the requirement for blood transfusion, and drain output in patients undergoing knee arthroplasty.

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References

  1. Moskal JT, Capps SG. Intra-articular Tranexamic Acid in Primary Total Knee Arthroplasty: Meta-analysis. J Knee Surg. 2018; 31(1): 56–67.
  2. Fillingham YA, Ramkumar DB, Jevsevar DS, et al. The Efficacy of Tranexamic Acid in Total Knee Arthroplasty: A Network Meta-Analysis. J Arthroplasty. 2018; 33(10): 3090–3098.e1.
  3. Pecold J, Al-Jeabory M, Krupowies M, et al. Tranexamic Acid for Shoulder Arthroplasty: A Systematic Review and Meta-Analysis. J Clin Med. 2021; 11(1): 48.
  4. Brusalis CM, Bostrom MPG, Richardson SS. Has Tranexamic Acid in Total Knee Arthroplasty Made Tourniquet Use Obsolete? HSS J. 2018; 14(3): 338–340.
  5. Fu Yu, Shi Z, Han B, et al. Comparing efficacy and safety of 2 methods of tranexamic acid administration in reducing blood loss following total knee arthroplasty: A meta-analysis. Medicine (Baltimore). 2016; 95(50): e5583.
  6. Lin C, Qi Y, Jie Li, et al. Is combined topical with intravenous tranexamic acid superior than topical, intravenous tranexamic acid alone and control groups for blood loss controlling after total knee arthroplasty: A meta-analysis. Medicine (Baltimore). 2016; 95(51): e5344.
  7. Mi B, Liu G, Lv H, et al. Is combined use of intravenous and intraarticular tranexamic acid superior to intravenous or intraarticular tranexamic acid alone in total knee arthroplasty? A meta-analysis of randomized controlled trials. J Orthop Surg Res. 2017; 12(1): 61.
  8. Bolam SM, O'Regan-Brown A, Paul Monk A, et al. Toxicity of tranexamic acid (TXA) to intra-articular tissue in orthopaedic surgery: a scoping review. Knee Surg Sports Traumatol Arthrosc. 2021; 29(6): 1862–1871.
  9. Goldstein M, Feldmann C, Wulf H, et al. Tranexamic Acid Prophylaxis in Hip and Knee Joint Replacement. Dtsch Arztebl Int. 2017; 114(48): 824–830.
  10. Park JH, Choi SW, Shin EHo, et al. The optimal protocol to reduce blood loss and blood transfusion after unilateral total knee replacement: Low-dose IA-TXA plus 30-min drain clamping versus drainage clamping for the first 3 h without IA-TXA. J Orthop Surg (Hong Kong). 2017; 25(3): 2309499017731626.
  11. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021; 372(71).
  12. Sterne JAC, Savović J, Page MJ, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019; 366: l4898.
  13. McGuinness LA, Higgins JPT. Risk-of-bias VISualization (robvis): An R package and Shiny web app for visualizing risk-of-bias assessments. Res Synth Methods. 2021; 12(1): 55–61.
  14. Alipour M, Tabari M, Keramati M, et al. Effectiveness of oral Tranexamic acid administration on blood loss after knee artroplasty: a randomized clinical trial. Transfus Apher Sci. 2013; 49(3): 574–577.
  15. Alshryda S, Mason J, Vaghela M, et al. Topical (intra-articular) tranexamic acid reduces blood loss and transfusion rates following total knee replacement: a randomized controlled trial (TRANX-K). J Bone Joint Surg Am. 2013; 95(21): 1961–1968.
  16. Alvarez JC, Santiveri FX, Ramos I, et al. Tranexamic acid reduces blood transfusion in total knee arthroplasty even when a blood conservation program is applied. Transfusion. 2008; 48(3): 519–525.
  17. Alvarez J, Santiveri FJ, Ramos MI, et al. Clinical trial on the effect of tranexamic acid on bleeding and fibrinolysis in primary hip and knee replacement. Rev Esp Anestesiol Reanim (Engl Ed). 2019; 66(6): 299–306.
  18. Antinolfi P, Innocenti B, Caraffa A, et al. Post-operative blood loss in total knee arthroplasty: knee flexion versus pharmacological techniques. Knee Surg Sports Traumatol Arthrosc. 2014; 22(11): 2756–2762.
  19. Benoni G, Fredin H. Fibrinolytic inhibition with tranexamic acid reduces blood loss and blood transfusion after knee arthroplasty: a prospective, randomised, double-blind study of 86 patients. J Bone Joint Surg Br. 1996; 78(3): 434–440.
  20. Bidolegui F, Arce G, Lugones A, et al. Tranexamic Acid Reduces Blood Loss and Transfusion in Patients Undergoing Total Knee Arthroplasty without Tourniquet: A Prospective Randomized Controlled Trial. Open Orthop J. 2014; 8: 250–254.
  21. Bradshaw A, Monoghan J, Campbell D. Oral tranexamic acid reduces blood loss in total knee replacement arthroplasty. C Orthopaedic Practice. 2012; 23(3): 209–212.
  22. Camarasa MA, Ollé G, Serra-Prat M, et al. Efficacy of aminocaproic, tranexamic acids in the control of bleeding during total knee replacement: a randomized clinical trial. Br J Anaesth. 2006; 96(5): 576–582.
  23. Cao G, Xie J, Huang Z, et al. Efficacy and safety of multiple boluses of oral versus intravenous tranexamic acid at reducing blood loss after primary total knee arthroplasty without a tourniquet: A prospective randomized clinical trial. Thromb Res. 2018; 171: 68–73.
  24. Chen X, Cao X, Yang C, et al. Effectiveness and Safety of Fixed-Dose Tranexamic Acid in Simultaneous Bilateral Total Knee Arthroplasty: A Randomized Double-Blind Controlled Trial. J Arthroplasty. 2016; 31(11): 2471–2475.
  25. Chiang ER, Chen KH, Wang ST, et al. Intra-articular Injection of Tranexamic Acid Reduced Postoperative Hemarthrosis in Arthroscopic Anterior Cruciate Ligament Reconstruction: A Prospective Randomized Study. Arthroscopy. 2019; 35(7): 2127–2132.
  26. Ellis MH, Fredman B, Zohar E, et al. The effect of tourniquet application, tranexamic acid, and desmopressin on the procoagulant and fibrinolytic systems during total knee replacement. J Clin Anesth. 2001; 13(7): 509–513.
  27. Engel JM, Hohaus T, Ruwoldt R, et al. Regional hemostatic status and blood requirements after total knee arthroplasty with and without tranexamic acid or aprotinin. Anesth Analg. 2001; 92(3): 775–780.
  28. Guerreiro JP, Badaro BS, Balbino JR, et al. Application of Tranexamic Acid in Total Knee Arthroplasty - Prospective Randomized Trial. Open Orthop J. 2017; 11: 1049–1057.
  29. Good L, Peterson E, Lisander B. Tranexamic acid decreases external blood loss but not hidden blood loss in total knee replacement. Br J Anaesth. 2003; 90(5): 596–599.
  30. Guzel Y, Gurcan OT, Golge UH, et al. Topical tranexamic acid versus autotransfusion after total knee arthroplasty. J Orthop Surg (Hong Kong). 2016; 24(2): 179–182.
  31. Hiippala ST, Strid LJ, Wennerstrand MI, et al. Tranexamic acid radically decreases blood loss and transfusions associated with total knee arthroplasty. Anesth Analg. 1997; 84(4): 839–844.
  32. Hiippala ST, Strid LJ, Wennerstrand MI, et al. Tranexamic acid (Cyklokapron) reduces perioperative blood loss associated with total knee arthroplasty. Br J Anaesth. 1995; 74(5): 534–537.
  33. Huang Z, Xie X, Li L, et al. Intravenous and Topical Tranexamic Acid Alone Are Superior to Tourniquet Use for Primary Total Knee Arthroplasty: A Prospective, Randomized Controlled Trial. J Bone Joint Surg Am. 2017; 99(24): 2053–2061.
  34. Ishida K, Tsumura N, Kitagawa A, et al. Intra-articular injection of tranexamic acid reduces not only blood loss but also knee joint swelling after total knee arthroplasty. Int Orthop. 2011; 35(11): 1639–1645.
  35. Jansen AJ, Andreica S, Claeys M, et al. Use of tranexamic acid for an effective blood conservation strategy after total knee arthroplasty. Br J Anaesth. 1999; 83(4): 596–601.
  36. Karaaslan F, Karaoğlu S, Mermerkaya MU, et al. Reducing blood loss in simultaneous bilateral total knee arthroplasty: combined intravenous-intra-articular tranexamic acid administration. A prospective randomized controlled trial. Knee. 2015; 22(2): 131–135.
  37. Kim TK, Chang CB, Kang YG, et al. Clinical value of tranexamic acid in unilateral and simultaneous bilateral TKAs under a contemporary blood-saving protocol: a randomized controlled trial. Knee Surg Sports Traumatol Arthrosc. 2014; 22(8): 1870–1878.
  38. Kim JK, Park JY, Lee DoY, et al. Optimal dose of topical tranexamic acid considering efficacy and safety in total knee arthroplasty: a randomized controlled study. Knee Surg Sports Traumatol Arthrosc. 2021; 29(10): 3409–3417.
  39. Kundu R, Das A, Basunia SR, et al. Does a single loading dose of tranexamic acid reduce perioperative blood loss and transfusion requirements after total knee replacement surgery? A randomized, controlled trial. J Nat Sci Biol Med. 2015; 6(1): 94–99.
  40. Gautam PL, Katyal S, Yamin M, et al. Effect of tranexamic acid on blood loss and transfusion requirement in total knee replacement in the Indian population: A case series. Indian J Anaesth. 2011; 55(6): 590–593.
  41. Lee SH, Cho KY, Khurana S, et al. Less blood loss under concomitant administration of tranexamic acid and indirect factor Xa inhibitor following total knee arthroplasty: a prospective randomized controlled trial. Knee Surg Sports Traumatol Arthrosc. 2013; 21(11): 2611–2617.
  42. Lee QJ, Ching WY, Wong YC. Blood Sparing Efficacy of Oral Tranexamic Acid in Primary Total Knee Arthroplasty: A Randomized Controlled Trial. Knee Surg Relat Res. 2017; 29(1): 57–62.
  43. Liu W, Yang C, Huang X, et al. Tranexamic Acid Reduces Occult Blood Loss, Blood Transfusion, and Improves Recovery of Knee Function after Total Knee Arthroplasty: A Comparative Study. J Knee Surg. 2018; 31(3): 239–246.
  44. MacGillivray RG, Tarabichi SB, Hawari MF, et al. Tranexamic acid to reduce blood loss after bilateral total knee arthroplasty: a prospective, randomized double blind study. J Arthroplasty. 2011; 26(1): 24–28.
  45. Maniar RN, Kumar G, Singhi T, et al. Most effective regimen of tranexamic acid in knee arthroplasty: a prospective randomized controlled study in 240 patients. Clin Orthop Relat Res. 2012; 470(9): 2605–2612.
  46. Molloy DO, Archbold HAP, Ogonda L, et al. Comparison of topical fibrin spray and tranexamic acid on blood loss after total knee replacement: a prospective, randomised controlled trial. J Bone Joint Surg Br. 2007; 89(3): 306–309.
  47. Motififard M, Tahririan MA, Saneie M, et al. Low Dose Perioperative Intravenous Tranexamic Acid in Patients Undergoing Total Knee Arthroplasty: A Double-Blind Randomized Placebo Controlled Clinical Trial. J Blood Transfus. 2015; 2015: 948304.
  48. Onodera T, Majima T, Sawaguchi N, et al. Risk of deep venous thrombosis in drain clamping with tranexamic acid and carbazochrome sodium sulfonate hydrate in total knee arthroplasty. J Arthroplasty. 2012; 27(1): 105–108.
  49. Orpen NM, Little C, Walker G, et al. Tranexamic acid reduces early post-operative blood loss after total knee arthroplasty: a prospective randomised controlled trial of 29 patients. Knee. 2006; 13(2): 106–110.
  50. 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(4): 698–707.
  51. Roy SP, Tanki UF, Dutta A, et al. Efficacy of intra-articular tranexamic acid in blood loss reduction following primary unilateral total knee arthroplasty. Knee Surg Sports Traumatol Arthrosc. 2012; 20(12): 2494–2501.
  52. Sa-Ngasoongsong P, Wongsak S, Chanplakorn P, et al. Efficacy of low-dose intra-articular tranexamic acid in total knee replacement; a prospective triple-blinded randomized controlled trial. BMC Musculoskelet Disord. 2013; 14: 340.
  53. Morales Santias M, Mas Martinez J, Sanz-Reig J, et al. Topical tranexamic acid in cemented primary total knee arthroplasty without tourniquet: a prospective randomized study. Eur J Orthop Surg Traumatol. 2020; 30(6): 1003–1008.
  54. Shen PF, Hou WL, Chen JB, et al. Effectiveness and safety of tranexamic acid for total knee arthroplasty: a prospective randomized controlled trial. Med Sci Monit. 2015; 21: 576–581.
  55. Shinde A, Sobti A, Maniar S, et al. Tranexamic acid reduces blood loss and need of blood transfusion in total knee arthroplasty: A prospective, randomized, double-blind study in Indian population. Asian J Transfus Sci. 2015; 9(2): 168–172.
  56. Sun Qi, Yu X, Wu J, et al. Efficacy of a Single Dose and an Additional Dose of Tranexamic Acid in Reduction of Blood Loss in Total Knee Arthroplasty. J Arthroplasty. 2017; 32(7): 2108–2112.
  57. Veien M, Sørensen JV, Madsen F, et al. Tranexamic acid given intraoperatively reduces blood loss after total knee replacement: a randomized, controlled study. Acta Anaesthesiol Scand. 2002; 46(10): 1206–1211.
  58. Volquind D, Zardo RA, Winkler BC, et al. [Use of tranexamic acid in primary total knee replacement: effects on perioperative blood loss]. Rev Bras Anestesiol. 2016; 66(3): 254–258.
  59. Wang Cg, Sun Zh, Liu J, et al. Safety and efficacy of intra-articular tranexamic acid injection without drainage on blood loss in total knee arthroplasty: A randomized clinical trial. Int J Surg. 2015; 20: 1–7.
  60. 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.
  61. Yang Y, Lv YM, Ding PJ, et al. The reduction in blood loss with intra-articular injection of tranexamic acid in unilateral total knee arthroplasty without operative drains: a randomized controlled trial. Eur J Orthop Surg Traumatol. 2015; 25(1): 135–139.
  62. Yen SH, Lin PC, Wu CT, et al. Comparison of Effects of a Thrombin-Based Hemostatic Agent and Topical Tranexamic Acid on Blood Loss in Patients with Preexisting Thromboembolic Risk Undergoing a Minimally Invasive Total Knee Arthroplasty. A Prospective Randomized Controlled Trial. Biomed Res Int. 2021; 2021: 2549521.
  63. Zhang S, Xie J, Cao G, et al. Six-Dose Intravenous Tranexamic Acid Regimen Further Inhibits Postoperative Fibrinolysis and Reduces Hidden Blood Loss following Total Knee Arthroplasty. J Knee Surg. 2021; 34(2): 224–232.
  64. Zhang X, Ma D, Pan J, et al. Effects of Different Applications of Tranexamic Acid on Perioperative Blood Transfusion Rate and Postoperative Pain in Unilateral Total Knee Arthroplasty. Adv Ther. 2021; 38(2): 1143–1154.
  65. Zohar E, Ellis M, Ifrach N, et al. The postoperative blood-sparing efficacy of oral versus intravenous tranexamic acid after total knee replacement. Anesth Analg. 2004; 99(6): 1679–1683.
  66. Al-Jeabory M, Gawel W, Gasecka A, et al. Tranexamic acid use in emergency medicine. Disaster and Emergency Medicine Journal. 2022; 7(1): 47–51.
  67. Boutsiadis A, Reynolds RJ, Saffarini Mo, et al. Factors that influence blood loss and need for transfusion following total knee arthroplasty. Ann Transl Med. 2017; 5(21): 418.
  68. Lee SY, Chong S, Balasubramanian D, et al. What is the Ideal Route of Administration of Tranexamic Acid in TKA? A Randomized Controlled Trial. Clin Orthop Relat Res. 2017; 475(8): 1987–1996.
  69. McLean M, McCall K, Smith IDM, et al. Tranexamic acid toxicity in human periarticular tissues. Bone Joint Res. 2019; 8(1): 11–18.
  70. Sun C, Zhang X, Ma Qi, et al. Impact of tourniquet during total knee arthroplasty when tranexamic acid was used: a meta-analysis of randomized controlled trials. J Orthop Surg Res. 2022; 17(1): 18.



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