Skip to main content
SpringerLink
Log in

Is tranexamic acid clinically effective and safe to prevent blood loss in total knee arthroplasty? A meta-analysis of 34 randomized controlled trials

  • Original Article
  • Published:
European Journal of Orthopaedic Surgery & Traumatology Aims and scope Submit manuscript

Abstract

Background

Tranexamic acid (TXA) is well established as a versatile intraarticular and intravenous (IV) antifibrinolytic agent that has been successfully used to control bleeding after total knee arthroplasty (TKA). The present meta-analysis aimed at assessing the effectiveness and safety of TXA in reducing blood loss and transfusion in TKA.

Methods

We searched the PubMed, Medline, Embase, Cochrane Central Register of Controlled Trials, and Google Scholar databases from 1966 to December 2013. Only randomized controlled trials (RCTs) were included in the present study. Two independent reviewers identified the eligible studies, assessed their methodological quality, and extracted data. The data were using fixed-effects or random-effects models with standard mean differences and risk ratios for continuous and dichotomous variables, respectively. Subgroup analysis was performed according to the IV or intraarticular administration of TXA.

Results

Thirty-four RCTs encompassing 2,594 patients met the inclusion criteria for our meta-analysis. Our meta-analysis indicated that when compared with the control group, the IV or intraarticular use of TXA significantly reduced total blood loss, postoperative blood loss, Hb loss, and transfusion rate as well as blood units transfused per patient after primary TKA, but did not reduce intraoperative blood loss. No significant difference in deep vein thrombosis (DVT), pulmonary embolism, or other adverse events among the study groups.

Conclusions

IV or intraarticular use of TXA for patients undergoing TKA is effective and safe for the reduction blood loss and blood transfusion requirements, yet does not increase the risk of postoperative DVT.

Level of evidence

Level II.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Park JH, Rasouli MR, Mortazavi SM, Tokarski AT, Maltenfort MG, Parvizi J (2013) Predictors of perioperative blood loss in total joint arthroplasty. J Bone Joint Surg Am 95(19):1777–1783

    Article  PubMed  Google Scholar 

  2. Banerjee S, Kapadia BH, Issa K, McElroy MJ, Khanuja HS, Harwin SF, Mont MA (2013) Postoperative blood loss prevention in total knee arthroplasty. J Knee Surg 26(6):395–400

    Article  PubMed  Google Scholar 

  3. Vielpeau C (2012) Perioperative bleeding and early mortality in hip and knee surgery. Orthop Traumatol Surg Res 98(5):475–476

    Article  CAS  PubMed  Google Scholar 

  4. Alshryda S, Mason J, Vaghela M, Sarda P, Nargol A, Maheswaran S, Tulloch C, Anand S, Logishetty R, Stothart B, Hungin AP (2013) 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 95(21):1961–1968

    Article  PubMed  Google Scholar 

  5. Schreiber GB, Busch MP, Kleinman SH, Korelitz JJ (1996) The risk of transfusion transmitted viral infections: the retrovirus epidemiology donor study. N Engl J Med 334(26):1685–1690

    Article  CAS  PubMed  Google Scholar 

  6. Muñoz M, Cobos A, Campos A (2014) Low vacuum re-infusion drains after total knee arthroplasty: is there a real benefit? Blood Transfus 12(Suppl 1):s173–s175

    PubMed Central  PubMed  Google Scholar 

  7. Horstmann W, Kuipers B, Ohanis D, Slappendel R, Kollen B, Verheyen C (2014) Autologous re-transfusion drain compared with no drain in total knee arthroplasty: a randomised controlled trial. Blood Transfus 12(Suppl 1):s176–s181

    PubMed Central  PubMed  Google Scholar 

  8. Perazzo P, Viganò M, De Girolamo L, Verde F, Vinci A, Banfi G, Romagnoli S (2013) Blood management and transfusion strategies in 600 patients undergoing total joint arthroplasty: an analysis of pre-operative autologous blood donation. Blood Transfus 11(3):370–376

    PubMed Central  PubMed  Google Scholar 

  9. Hardy JF, Desroches J (1992) Natural and synthetic antifibrino-lytics in cardiac surgery. Can J Anaesth 39(4):353–365

    Article  CAS  PubMed  Google Scholar 

  10. Abrishami A, Chung F, Wong J (2009) Topical application of antifibrinolytic drugs for on-pump cardiac surgery: a systematic review and meta-analysis. Can J Anaesth 56(3):202–212

    Article  PubMed  Google Scholar 

  11. Ker K, Edwards P, Perel P, Shakur H, Roberts I (2012) Effect of tranexamic acid on surgical bleeding: systematic review and cumulative meta-analysis. BMJ 344:e3054

    Article  PubMed Central  PubMed  Google Scholar 

  12. Zhang H, Chen J, Chen F, Que W (2012) 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 20(9):1742–1752

    Article  PubMed  Google Scholar 

  13. Aguilera X, Martinez-Zapata MJ, Bosch A, Urrútia G, González JC, Jordan M, Gich I, Maymó RM, Martínez N, Monllau JC, Celaya F, Fernández JA (2013) Efficacy and safety of fibrin glue and tranexamic Acid to prevent postoperative blood loss in total knee arthroplasty: a randomized controlled clinical trial. J Bone Joint Surg Am 95(22):2001–2007

    Article  CAS  PubMed  Google Scholar 

  14. Chareancholvanich K, Siriwattanasakul P, Narkbunnam R, Pornrattanamaneewong C (2012) Temporary clamping of drain combined with tranexamic acid reduce blood loss after total knee arthroplasty: a prospective randomized controlled trial. BMC Musculoskelet Disord 13:124

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Georgiadis AG, Muh SJ, Silverton CD, Weir RM, Laker MW (2013) A prospective double-blind placebo controlled trial of topical tranexamic acid in total knee arthroplasty. J Arthroplasty 28(8 Suppl):78–82

    Article  PubMed  Google Scholar 

  16. Kim TK, Chang CB, Kang YG, Seo ES, Lee JH, Yun JH, Lee SH (2014) 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 22(8):1870–1878

    Article  PubMed  Google Scholar 

  17. Lee SH, Cho KY, Khurana S, Kim KI (2013) 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 21(11):2611–2617

    Article  PubMed  Google Scholar 

  18. Martin JG, Cassatt KB, Kincaid-Cinnamon KA, Westendorf DS, Garton AS, Lemke JH (2014) Topical administration of tranexamic acid in primary total hip and total knee arthroplasty. J Arthroplasty 29(5):889–894

    Article  PubMed  Google Scholar 

  19. Pachauri A, Acharya KK, Tiwari AK (2013) The effect of tranexamic acid on hemoglobin levels during total knee arthroplasty. Am J Ther 21(5):366–370

  20. Roy SP, Tanki UF, Dutta A, Jain SK, Nagi ON (2012) Efficacy of intra-articular tranexamic acid in blood loss reduction following primary unilateral total knee arthroplasty. Knee Surg Sports Traumatol Arthrosc 20(12):2494–2501

    Article  PubMed  Google Scholar 

  21. Seo JG, Moon YW, Park SH, Kim SM, Ko KR (2013) The comparative efficacies of intra-articular and IV tranexamic acid for reducing blood loss during total knee arthroplasty. Knee Surg Sports Traumatol Arthrosc 21(8):1869–1874

    Article  PubMed  Google Scholar 

  22. Abrishami A (2010) Timing and volume of topical tranexamic acid administration for postoperative blood loss in total knee arthroplasty. Can J Anesth 51:S142–S143

    Google Scholar 

  23. Alvarez JC, Santiveri FX, Ramos I, Vela E, Puig L, Escolano F (2008) Tranexamic acid reduces blood transfusion in total knee arthroplasty even when a blood conservation program is applied. Transfusion 48(3):519–525

    Article  PubMed  Google Scholar 

  24. Benoni G, Fredin H (1996) 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 78(3):434–440

    CAS  PubMed  Google Scholar 

  25. Camarasa MA, Ollé G, Serra-Prat M, Martín A, Sánchez M, Ricós P, Pérez A, Opisso L (2006) Efficacy of aminocaproic, tranexamic acids in the control of bleeding during total knee replacement: a randomized clinical trial. Br J Anaesth 96(5):576–582

    Article  CAS  PubMed  Google Scholar 

  26. Charoencholvanich K, Siriwattanasakul P (2011) Tranexamic acid reduces blood loss and blood transfusion after TKA: a prospective randomized controlled trial. Clin Orthop Relat Res 469(10):2874–2880

    Article  PubMed Central  PubMed  Google Scholar 

  27. Ellis MH, Fredman B, Zohar E, Ifrach N, Jedeikin R (2001) The effect of tourniquet application, tranexamic acid, and desmopressin on the procoagulant and fibrinolytic systems during total knee replacement. J Clin Anesth 13(7):509–513

    Article  CAS  PubMed  Google Scholar 

  28. Engel JM, Hohaus T, Ruwoldt R, Menges T, Jürgensen I, Hempelmann G (2001) Regional hemostatic status and blood requirements after total knee arthroplasty with and without tranexamic acid or aprotinin. Anesth Analg 92(3):775–780

    Article  CAS  PubMed  Google Scholar 

  29. Gautam PL, Katyal S, Yamin M, Singh A (2011) Effect of tranexamic acid on blood loss and transfusion requirement in total knee replacement in the Indian population: a case series. Indian J Anaesth 55(6):590–593

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Good L, Peterson E, Lisander B (2003) Tranexamic acid decreases external blood loss but not hidden blood loss in total knee replacement. Br J Anaesth 90(5):596–599

    Article  CAS  PubMed  Google Scholar 

  31. Hiippala ST, Strid LJ, Wennerstrand MI, Arvela JV, Niemelä HM, Mäntylä SK, Kuisma RP, Ylinen JE (1997) Tranexamic acid radically decreases blood loss and transfusions associated with total knee arthroplasty. Anesth Analg 84(4):839–844

    CAS  PubMed  Google Scholar 

  32. Hiippala S, Strid L, Wennerstrand M, Arvela V, Mäntylä S, Ylinen J, Niemelä H (1995) Tranexamic acid (Cyklokapron) reduces perioperative blood loss associated with total knee arthroplasty. Br J Anaesth 74(5):534–537

    Article  CAS  PubMed  Google Scholar 

  33. Ishida K, Tsumura N, Kitagawa A, Hamamura S, Fukuda K, Dogaki Y, Kubo S, Matsumoto T, Matsushita T, Chin T, Iguchi T, Kurosaka M, Kuroda R (2011) Intra-articular injection of tranexamic acid reduces not only blood loss but also knee joint swelling after total knee arthroplasty. Int Orthop 35(11):1639–1645

    Article  PubMed Central  PubMed  Google Scholar 

  34. Jansen AJ, Andreica S, Claeys M, D’Haese J, Camu F, Jochmans K (1999) Use of tranexamic acid for an effective blood conservation strategy after total knee arthroplasty. Br J Anaesth 83(4):596–601

    Article  CAS  PubMed  Google Scholar 

  35. Kakar PN, Gupta N, Govil P, Shah V (2009) Efficacy and safety of tranexamic acid in control of bleeding following TKR: a randomized clinical trial. Indian J Anaesth 53(6):667–671

    PubMed Central  CAS  PubMed  Google Scholar 

  36. Maniar RN, Kumar G, Singhi T, Nayak RM, Maniar PR (2012) Most effective regimen of tranexamic acid in knee arthroplasty: a prospective randomized controlled study in 240 patients. Clin Orthop Relat Res 470(9):2605–2612

    Article  PubMed Central  PubMed  Google Scholar 

  37. McConnell JS, Shewale S, Munro NA, Shah K, Deakin AH, Kinninmonth AW (2012) Reducing blood loss in primary knee arthroplasty: a prospective randomised controlled trial of tranexamic acid and fibrin spray. Knee 19(4):295–298

    Article  PubMed  Google Scholar 

  38. Molloy DO, Archbold HA, Ogonda L, McConway J, Wilson RK, Beverland DE (2007) 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 89(3):306–309

    Article  CAS  PubMed  Google Scholar 

  39. Onodera T, Majima T, Sawaguchi N, Kasahara Y, Ishigaki T, Minami A (2012) Risk of deep venous thrombosis in drain clamping with tranexamic acid and carbazochrome sodium sulfonate hydrate in total knee arthroplasty. J Arthroplasty 27(1):105–108

    Article  PubMed  Google Scholar 

  40. Orpen NM, Little C, Walker G, Crawfurd EJ (2006) Tranexamic acid reduces early post-operative blood loss after total knee arthroplasty: a prospective randomised controlled trial of 29 patients. Knee 13(2):106–110

    Article  PubMed  Google Scholar 

  41. Tanaka N, Sakahashi H, Sato E, Hirose K, Ishima T, Ishii S (2001) Timing of the administration of tranexamic acid for maximum reduction in blood loss in arthroplasty of the knee. J Bone Joint Surg Br 83(5):702–705

    Article  CAS  PubMed  Google Scholar 

  42. Veien M, Sørensen JV, Madsen F, Juelsgaard P (2002) Tranexamic acid given intraoperatively reduces blood loss after total knee replacement: a randomized, controlled study. Acta Anaesthesiol Scand 46(10):1206–1211

    Article  CAS  PubMed  Google Scholar 

  43. Wong J, Abrishami A, El Beheiry H, Mahomed NN, Roderick Davey J, Gandhi R, Syed KA, Muhammad Ovais Hasan S, De Silva Y, Chung F (2010) Topical application of tranexamic acid reduces postoperative blood loss in total knee arthroplasty: a randomized, controlled trial. J Bone Joint Surg Am 92(15):2503–2513

    Article  PubMed  Google Scholar 

  44. Zhang F, Gao Z, Yu J (2007) Clinical comparative studies on effect of tranexamic acid on blood loss associated with total knee arthroplasty. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 21(12):1302–1304

    CAS  PubMed  Google Scholar 

  45. Zohar E, Ellis M, Ifrach N, Stern A, Sapir O, Fredman B (2004) The postoperative blood-sparing efficacy of oral versus intravenous tranexamic acid after total knee replacement. Anesth Analg 99(6):1679–1683

    Article  PubMed  Google Scholar 

  46. Tan J, Chen H, Liu Q, Chen C, Huang W (2013) A meta-analysis of the effectiveness and safety of using tranexamic acid in primary unilateral total knee arthroplasty. J Surg Res 184(2):880–887

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Orthopaedics, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, 314 An Shan Xi Road, Nan Kai District, Tianjin, 300000, People’s Republic of China

    Qiang Wu, Hong-An Zhang, Shi-Long Liu, Tao Meng, Xin Zhou & Ping Wang

Authors
  1. Qiang Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hong-An Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shi-Long Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tao Meng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xin Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ping Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ping Wang.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wu, Q., Zhang, HA., Liu, SL. et al. Is tranexamic acid clinically effective and safe to prevent blood loss in total knee arthroplasty? A meta-analysis of 34 randomized controlled trials. Eur J Orthop Surg Traumatol 25, 525–541 (2015). https://doi.org/10.1007/s00590-014-1568-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00590-014-1568-z

Keywords

Search

Navigation