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Archives of Orthopaedic and Trauma Surgery

, Volume 135, Issue 7, pp 1017–1025 | Cite as

Topical and intravenous tranexamic acid reduce blood loss compared to routine hemostasis in total knee arthroplasty: a multicenter, randomized, controlled trial

  • X Aguilera
  • M. J. Martínez-ZapataEmail author
  • P. Hinarejos
  • M. Jordán
  • J. Leal
  • J. C. González
  • J. C. Monllau
  • F. Celaya
  • A. Rodríguez-Arias
  • J. A. Fernández
  • X. Pelfort
  • L. l. Puig-Verdie
Knee Arthroplasty

Abstract

Introduction

Tranexamic acid (TXA) is becoming widely used in orthopedic surgery to reduce blood loss and transfusion requirements, but consensus is lacking regarding the optimal route and dose of administration. The aim of this study was to compare the efficacy and safety of topical and intravenous routes of TXA with routine hemostasis in patients undergoing primary total knee arthroplasty (TKA).

Materials and methods

We performed a randomized, multicenter, parallel, open-label clinical trial in adult patients undergoing primary TKA. Patients were divided into three groups of 50 patients each: Group 1 received 1 g topical TXA, Group 2 received 2 g intravenous TXA, and Group 3 (control group) had routine hemostasis. The primary outcome was total blood loss. Secondary outcomes were hidden blood loss, blood collected in drains, transfusion rate, number of blood units transfused, adverse events, and mortality.

Results

One hundred and fifty patients were included. Total blood loss was 1021.57 (481.09) mL in Group 1, 817.54 (324.82) mL in Group 2 and 1415.72 (595.11) mL in Group 3 (control group). Differences in total blood loss between the TXA groups and the control group were clinically and statistically significant (p < 0.001). In an exploratory analysis differences between the two TXA groups were not statistically significant (p = 0.073) Seventeen patients were transfused. Transfusion requirements were significantly higher in Group 3 (p = 0.005). No significant differences were found between groups regarding adverse events.

Conclusion

We found that 1 g of topical TXA and 2 g of intravenous TXA were both safe strategies and more effective than routine hemostasis to reduce blood loss and transfusion requirements after primary TKA.

Level of evidence

I.

Keywords

Topical and intravenous tranexamic acid Total knee arthroplasty Blood loss Transfusion 

Notes

Acknowledgments

The authors wish to thank Esther Cánovas Martínez and Mercedes Subiela for data collection, Gemma Horta for logistic support, Sebastíà Videla for assistance with methodology and the revision of the manuscript, the staff at the Orthopedic Surgery Department, the secretary staff of the Iberoamerican Cochrane Centre-Clinical Epidemiology and Public Health Department, and Carolyn Newey for editing the text. The authors would also like to convey thanks to Rottapharm/Madaus for providing the tranexamic acid ampoules. Dr. Xavier Aguilera is a PhD candidate in the Surgery Department, Universitat Autónoma de Barcelona. Spain. This project was funded principally by a grant from the Spanish Ministry of Health and Social Policy to promote independent clinical research 2010 (EC10-73).

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Fahmy NR, Patel DG (1981) Hemostatic changes and postoperative deep-vein thrombosis associated with use of a pneumatic tourniquet. J Bone Joint Surg Am 63(3):461–465PubMedGoogle Scholar
  2. 2.
    Petäjä J, Myllynen P, Myllylä G, Vahtera E (1987) Fibrinolysis after application of pneumatic tourniquet. Acta Chir Scand 153(11–12):647–651PubMedGoogle Scholar
  3. 3.
    Kozek-Langenecker SA, Afshari A, Albaladejo P, Santullano CA, De Robertis E, Filipescu DC, Fries D, Görlinger K, Haas T, Imberger G, Jacob M, Lancé M, Llau J, Mallett S, Meier J, Rahe-Meyer N, Samama CM, Smith A, Solomon C, Van der Linden P, Wikkelsø AJ, Wouters P, Wyffels P (2013) Management of severe perioperative bleeding: guidelines from the European Society of Anaesthesiology. Eur J Anaesthesiol 30(6):270–382PubMedCrossRefGoogle Scholar
  4. 4.
    Goodnough LT, Maniatis A, Earnshaw P, Benoni G, Beris P, Bisbe E, Fergusson DA, Gombotz H, Habler O, Monk TG, Ozier Y, Slappendel R, Szpalski M (2011) Detection, evaluation, and management of preoperative anaemia in the elective orthopaedic surgical patient: NATA guidelines. Br J Anaesth 106(1):13–22PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Kelley TC, Tucker KK, Adams MJ, Dalury DF (2014) Use of tranexamic acid results in decreased blood loss and decreased transfusions in patients undergoing staged bilateral total knee arthroplasty. Transfusion 54(1):26–30PubMedCrossRefGoogle Scholar
  6. 6.
    Henry DA, Carless PA, Moxey AJ, O’Connell D, Stokes BJ, Fergusson DA, Ker K (2011) Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion. Cochrane Database Syst Rev 19(1):CD001886Google Scholar
  7. 7.
    Ker K, Beecher D, Roberts I (2013) Topical application of tranexamic acid for the reduction of bleeding. Cochrane Database Syst Rev 23(7):CD010562Google Scholar
  8. 8.
    Kim TK, Chang CB, Koh IJ (2014) Practical issues for the use of tranexamic acid in total knee arthroplasty: a systematic review. Knee Surg Sports Traumatol Arthrosc 22(8):1849–1858PubMedCrossRefGoogle Scholar
  9. 9.
    Yang ZG, Chen WP, Wu LD (2012) Effectiveness and safety of tranexamic acid in reducing blood loss in total knee arthroplasty: a meta-analysis. J Bone Joint Surg Am 94(13):1153–1159PubMedCrossRefGoogle Scholar
  10. 10.
    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):1742–1752PubMedCrossRefGoogle Scholar
  11. 11.
    Panteli M, Papakostidis C, Dahabreh Z, Giannoudis PV (2013) Topical tranexamic acid in total knee replacement: a systematic review and meta-analysis. Knee 20(5):300–309PubMedCrossRefGoogle Scholar
  12. 12.
    Hedge C, Wasnik S, Kulkarni S, Pradhan S, Shetty V (2013) Simultaneous bilateral computer assisted total knee arthroplasty: the effect of intravenous or intraarticular tranexamic acid. J Arthroplasty 28(10):1888–1891CrossRefGoogle Scholar
  13. 13.
    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):2605–2612PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    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):1080–1083Google Scholar
  15. 15.
    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):1869–1874PubMedCrossRefGoogle Scholar
  16. 16.
    Gomez-Barrena E, Ortega-Andreu M, Padilla-Eguiluz NG, Pérez-Chrzanowska H, Figueredo-Zalve R (2014) 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 96(23):1937–1944PubMedCrossRefGoogle Scholar
  17. 17.
    Huang Z, Ma J, Shen B, Pei F (2014) Combination of intravenous and topical application of tranexamic acid in primary total knee arthroplasty: a prospective randomized controlled trial. J Arthroplasty 29(12):2342–2346PubMedCrossRefGoogle Scholar
  18. 18.
    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):1525–1527PubMedCrossRefGoogle Scholar
  19. 19.
    Wind TC, Barfield WR, Moskal JT (2013) The effect of tranexamic acid on blood loss and transfusion rate in primary total knee arthroplasty. J Arthroplasty 28(7):1080–1083PubMedCrossRefGoogle Scholar
  20. 20.
    Nadler SB, Hidalgo JU, Bloch T (1962) Prediction of blood volume in normal human adults. Surgery 51(2):224–232PubMedGoogle Scholar
  21. 21.
    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):702–705PubMedCrossRefGoogle Scholar
  22. 22.
    Aguilera X, Martínez-Zapata MJ, Bosch A, Urrutia G, González JC, Jordán 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):2001–2007PubMedCrossRefGoogle Scholar
  23. 23.
    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):2503–2513PubMedCrossRefGoogle Scholar
  24. 24.
    Chimento GF, Huff T, Ochsner JL, Meyer M, Brandner L, Babin S (2013) An evaluation of the use of topical tranexamic acid in total knee arthroplasty. J Artroplasty 28(Suppl 1):74–77CrossRefGoogle Scholar
  25. 25.
    Gilbody J, Dhotar HS, Perruccio AV, Davey JR (2014) Topical tranexamic acid reduces transfusion rates in total hip and knee arthroplasty. J Arthroplasty 29(4):681–684PubMedCrossRefGoogle Scholar
  26. 26.
    Konig G, Hamlin BR, Waters JH (2013) Topical tranexamic acid reduces blood loss and transfusion rates in total hip and total knee arthroplasty. J Arthroplasty 28(9):1473–1476PubMedCrossRefGoogle Scholar
  27. 27.
    Sarzaeem MM, Razi M, Kazemian G, Moghaddam ME, Rasi AM, Karimi M (2014) Comparing efficacy of three methods of tranexamic acid administration in reducing hemoglobin drop following total knee arthroplasty. J Arthroplasty 29(8):1521–1524PubMedCrossRefGoogle Scholar
  28. 28.
    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):1961–1968PubMedCrossRefGoogle Scholar
  29. 29.
    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):1639–1645PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    Sa-Ngasoongsong P, Channoom T, Kawinwonggowit V, Woratanarat P, Chanplakorn P, Wibulpolprasert B, Wongsak S, Udomsubpayakul U, Wechmongkolgorn S, Lekpittaya N (2011) Postoperative blood loss reduction in computer-assisted surgery total knee replacement by low dose intra-articular tranexamic acid injection together with 2-h clamp drain: a prospective triple-blinded randomized controlled trial. Orthop Rev (Pavia) 3(2):e1. doi: 10.4081/or.2011.e1232 CrossRefGoogle Scholar
  31. 31.
    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):889–894PubMedCrossRefGoogle Scholar
  32. 32.
    Mutsuzaki H, Ikeda K (2012) Intra-articular injection of tranexamic acid via a drain plus rain-clamping to reduce blood loss in cementless total knee arthroplasty. J Orthop Surg Res 7:32. doi: 10.1186/1749-799X-7-32 PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    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):2494–2501PubMedCrossRefGoogle Scholar
  34. 34.
    Diamond PT, Conaway MR, Mody SH, Bhirangi K (2006) Influence of haemoglobin levels on inpatient rehabilitation outcomes after total knee arthroplasty. J Arthroplasty 21(5):636–641PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • X Aguilera
    • 1
  • M. J. Martínez-Zapata
    • 2
    Email author
  • P. Hinarejos
    • 3
  • M. Jordán
    • 1
  • J. Leal
    • 3
  • J. C. González
    • 1
  • J. C. Monllau
    • 3
  • F. Celaya
    • 1
  • A. Rodríguez-Arias
    • 4
  • J. A. Fernández
    • 5
  • X. Pelfort
    • 3
  • L. l. Puig-Verdie
    • 3
  1. 1.Orthopedic Surgery and Traumatology DepartmentHospital de la Santa Creu i Sant PauBarcelonaSpain
  2. 2.Iberoamerican Cochrane Centre, CIBER de Epidemiología y Salud Pública (CIBERESP), IIB Sant PauBarcelonaSpain
  3. 3.Orthopedic Surgery and Traumatology DepartmentParc de Salut MarBarcelonaSpain
  4. 4.Pharmacy DepartmentHospital de la Santa Creu i Sant PauBarcelonaSpain
  5. 5.Anesthesiology DepartmentHospital de la Santa Creu i Sant PauBarcelonaSpain

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