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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

  • Knee Arthroplasty
  • Published:
Archives of Orthopaedic and Trauma Surgery Aims and scope Submit manuscript

Abstract

Background

Tranexamic acid (TXA) in orthopedics has recently been gaining favor due to its efficacy and ease of use, both in intravenous (IV) and intraarticular (IA) usage. However, because of safety concerns with IV administration, there has been a growing interest in the IA use of TXA to prevent bleeding.

Materials and methods

This study conducted a systematic review and meta-analysis that included 31 randomized, controlled trials in which the effect of systemic and topical TXA on total blood loss (TBL), rates of transfusion, and thromboembolic events was investigated.

Results

Compared to the control, the IA administration of TXA led to the significant reduction of mean TBL (p < 0.001), rate of transfusion (p < 0.001), and reduction of rate of thromboembolic events (p = 0.29). Compared to the control group, the IV administration of TXA resulted in significant reduction of mean TBL (p < 0.001), rate of transfusion (p < 0.001), and rate of thromboembolic events (p = 0.66). Although no significant differences in efficacy and safety between the IA and IV administration of TXA were found, the IA method was safer than the IV method in that it reduced rate of transfusion and thromboembolic events.

Conclusion

This study showed that TXA leads to significant reductions in TBL and the rate of allogeneic transfusions. Generally, no significant difference was detected between IA and IV administration of TXA; however, more studies with focus on safety and efficacy are warranted.

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References

  1. Kurtz S, Ong K, Lau E, Mowat F, Halpern M (2007) Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to 2030. J Bone Joint Surg Am 89(4):780–785

    Article  PubMed  Google Scholar 

  2. Kirwan JR, Currey HL, Freeman MA, Snow S, Young PJ (1994) Overall long-term impact of total hip and knee joint replacement surgery on patients with osteoarthritis and rheumatoid arthritis. Br J Rheumatol 33(4):357–360

    Article  CAS  PubMed  Google Scholar 

  3. Prasad N, Padmanabhan V, Mullaji A (2007) Blood loss in total knee arthroplasty: an analysis of risk factors. Int Orthop 31(1):39–44

    Article  PubMed Central  PubMed  Google Scholar 

  4. Cushner FD, Friedman RJ (1991) Blood loss in total knee arthroplasty. Clin Orthop Relat Res 269:98–101

    PubMed  Google Scholar 

  5. Bower WF, Jin L, Underwood MJ, Lam YH, Lai PB (2010) Peri-operative blood transfusion increases length of hospital stay and number of postoperative complications in non-cardiac surgical patients. Hong Kong Med J 16(2):116–120

    CAS  PubMed  Google Scholar 

  6. Spahn DR (2010) Anemia and patient blood management in hip and knee surgery: a systematic review of the literature. Anesthesiology 113(2):482–495

    Article  PubMed  Google Scholar 

  7. Rajesparan K, Biant LC, Ahmad M, Field RE (2009) The effect of an intravenous bolus of tranexamic acid on blood loss in total hip replacement. J Bone Joint Surg Br 91(6):776–783

    Article  CAS  PubMed  Google Scholar 

  8. 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 (table of contents)

    Article  PubMed  Google Scholar 

  9. Eubanks JD (2010) Antifibrinolytics in major orthopaedic surgery. J Am Acad Orthop Surg 18(3):132–138

    PubMed  Google Scholar 

  10. Mongan PD, Brown RS, Thwaites BK (1998) Tranexamic acid and aprotinin reduce postoperative bleeding and transfusions during primary coronary revascularization. Anesth Analg 87(2):258–265

    CAS  PubMed  Google Scholar 

  11. Boylan JF, Klinck JR, Sandler AN, Arellano R, Greig PD, Nierenberg H et al (1996) Tranexamic acid reduces blood loss, transfusion requirements, and coagulation factor use in primary orthotopic liver transplantation. Anesthesiology 85(5):1043–1048 (discussion 30A–31A)

    Article  CAS  PubMed  Google Scholar 

  12. Wellington K, Wagstaff AJ (2003) Tranexamic acid: a review of its use in the management of menorrhagia. Drugs 63(13):1417–1433

    Article  CAS  PubMed  Google Scholar 

  13. Ipema HJ, Tanzi MG (2012) Use of topical tranexamic acid or aminocaproic acid to prevent bleeding after major surgical procedures. Ann Pharmacother 46(1):97–107

    Article  CAS  PubMed  Google Scholar 

  14. Gybel M, Kristensen K, Roseva-Nielsen N (2013) Cardiac arrest caused by massive pulmonary embolism during treatment with tranexamic acid. Ugeskr Laeger 175(20):1426–1427

    PubMed  Google Scholar 

  15. Taparia M, Cordingley FT, Leahy MF (2002) Pulmonary embolism associated with tranexamic acid in severe acquired haemophilia. Eur J Haematol 68(5):307–309

    Article  PubMed  Google Scholar 

  16. Krivokuca I, Lammers JW (2011) Recurrent pulmonary embolism associated with a hemostatic drug: tranexamic acid. Clin Appl Thromb Hemost Off J Int Acad Clin Appl Thromb Hemost 17(1):106–107

    Article  CAS  Google Scholar 

  17. Bruce-Brand R, Dragomir R, Baker J, Harty J (2013) Cerebrovascular infarction following bilateral total knee arthroplasty and tranexamic acid administration. Acta Orthop Belg 79(3):351–354

    PubMed  Google Scholar 

  18. Gandhi R, Evans HM, Mahomed SR, Mahomed NN (2013) Tranexamic acid and the reduction of blood loss in total knee and hip arthroplasty: a meta-analysis. BMC Res Notes 6:184

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. 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 

  20. Alshryda S, Sukeik M, Sarda P, Blenkinsopp J, Haddad FS, Mason JM (2014) A systematic review and meta-analysis of the topical administration of tranexamic acid in total hip and knee replacement. Bone Joint J 96-B(8):1005–1015

    Article  CAS  PubMed  Google Scholar 

  21. Kagoma YK, Crowther MA, Douketis J, Bhandari M, Eikelboom J, Lim W (2009) Use of antifibrinolytic therapy to reduce transfusion in patients undergoing orthopedic surgery: a systematic review of randomized trials. Thrombosis Res 123(5):687–696

    Article  CAS  Google Scholar 

  22. Sa-Ngasoongsong P, Channoom T, Kawinwonggowit V, Woratanarat P, Chanplakorn P, Wibulpolprasert B et al (2011) Postoperative blood loss reduction in computer-assisted surgery total knee replacement by low dose intra-articular tranexamic acid injection together with 2-hour clamp drain: a prospective triple-blinded randomized controlled trial. Orthop Rev 3(2):e12

    Article  Google Scholar 

  23. Sa-Ngasoongsong P, Wongsak S, Chanplakorn P, Woratanarat P, Wechmongkolgorn S, Wibulpolprasert B et al (2013) Efficacy of low-dose intra-articular tranexamic acid in total knee replacement; a prospective triple-blinded randomized controlled trial. BMC Musculoskelet Disord 14:340

    Article  PubMed Central  PubMed  Google Scholar 

  24. Alshryda S, Mason J, Vaghela M, Sarda P, Nargol A, Maheswaran S et al (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 

  25. 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 

  26. 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 

  27. Camarasa MA, Olle G, Serra-Prat M, Martin A, Sanchez M, Ricos P et al (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 

  28. 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 

  29. 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 

  30. 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 

  31. 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 

  32. Hiippala S, Strid L, Wennerstrand M, Arvela V, Mantyla S, Ylinen J et al (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. Hiippala ST, Strid LJ, Wennerstrand MI, Arvela JV, Niemela HM, Mantyla SK et al (1997) Tranexamic acid radically decreases blood loss and transfusions associated with total knee arthroplasty. Anesth Analg 84(4):839–844

    CAS  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. 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 Off J ESSKA 21(11):2611–2617

    Article  Google Scholar 

  37. MacGillivray RG, Tarabichi SB, Hawari MF, Raoof NT (2011) Tranexamic acid to reduce blood loss after bilateral total knee arthroplasty: a prospective, randomized double blind study. J Arthroplasty 26(1):24–28

    Article  PubMed  Google Scholar 

  38. 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 

  39. Oremus K, Sostaric S, Trkulja V, Haspl M (2014) Influence of tranexamic acid on postoperative autologous blood retransfusion in primary total hip and knee arthroplasty: a randomized controlled trial. Transfusion 54(1):31–41

    Article  CAS  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. 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 Off J ESSKA 20(12):2494–2501

    Article  Google Scholar 

  42. Wong J, Abrishami A, El Beheiry H, Mahomed NN, Roderick Davey J, Gandhi R et al (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 

  43. 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 

  44. 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 

  45. 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 

  46. Aguilera X, Martinez-Zapata MJ, Bosch A, Urrutia G, Gonzalez JC, Jordan M et al (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 

  47. Engel JM, Hohaus T, Ruwoldt R, Menges T, Jurgensen 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 

  48. Ishida K, Tsumura N, Kitagawa A, Hamamura S, Fukuda K, Dogaki Y et al (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 

  49. 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 

  50. Veien M, Sorensen 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 

  51. 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 

  52. Mylod AG Jr, France MP, Muser DE, Parsons JR (1990) Perioperative blood loss associated with total knee arthroplasty. A comparison of procedures performed with and without cementing. J Bone Joint Surg Am 72(7):1010–1012

    PubMed  Google Scholar 

  53. Raut VV, Stone MH, Wroblewski BM (1993) Reduction of postoperative blood loss after press-fit condylar knee arthroplasty with use of a femoral intramedullary plug. J Bone Joint Surg Am 75(9):1356–1357

    CAS  PubMed  Google Scholar 

  54. Modig J, Karlstrom G (1987) Intra- and post-operative blood loss and haemodynamics in total hip replacement when performed under lumbar epidural versus general anaesthesia. Eur J Anaesthesiol 4(5):345–355

    CAS  PubMed  Google Scholar 

  55. Soni A, Saini R, Gulati A, Paul R, Bhatty S, Rajoli SR (2014) Comparison between intravenous and intra-articular regimens of tranexamic acid in reducing blood loss during total knee arthroplasty. J Arthroplasty 29(8):1525–1527

    Article  PubMed  Google Scholar 

  56. Patel JN, Spanyer JM, Smith LS, Huang J, Yakkanti MR, Malkani AL (2014) Comparison of intravenous versus topical tranexamic acid in total knee arthroplasty: a prospective randomized study. J Arthroplasty 29(8):1528–1531

    Article  PubMed  Google Scholar 

  57. White RH, Romano PS, Zhou H, Rodrigo J, Bargar W (1998) Incidence and time course of thromboembolic outcomes following total hip or knee arthroplasty. Arch Intern Med 158(14):1525–1531

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We are all thankful for the editing assistance that Mahboobeh Fereidan-Esfahani (Isfahan University of Medical Sciences, Iran) provided.

Conflict of interest

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Authors and Affiliations

  1. Orthopaedic Surgery Department, Crona Clinik, Eberhard Karls University, Tuebingen, Germany

    Hamidreza Shemshaki

  2. Department of Biological Sciences, California State University, Stanislaus, Turlock, CA, 95382, USA

    Sayed Mohammad Amin Nourian

  3. Najafabad Azad University of Medical Sciences, Najafabad, Iran

    Niloofaralsadat Nourian

  4. Department of Orthopedic Surgery, Saadi Hospital, Isfahan, Iran

    Masoudhatef Dehghani

  5. Isfahan University of Medical Sciences, Isfahan, Iran

    Masoud Mokhtari

  6. Department of Orthopedic Surgery, University of Munich (LMU), Campus Grosshadern, Marchioninistraße 15, 81377, Munich, Germany

    Farhad Mazoochian

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  1. Hamidreza Shemshaki
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Correspondence to Hamidreza Shemshaki.

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Shemshaki, H., Nourian, S.M.A., Nourian, N. et al. 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 135, 573–588 (2015). https://doi.org/10.1007/s00402-015-2189-7

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  • DOI: https://doi.org/10.1007/s00402-015-2189-7

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