Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

The use of factor Xa inhibitors following opening-wedge high tibial osteotomy for venous thromboembolism prophylaxis



This study aimed to investigate the incidence of venous thromboembolism (VTE) after medial opening-wedge high tibial osteotomy (OWHTO) and evaluate the efficacy and safety of edoxaban for the prevention of VTE in patients undergoing OWHTO.


A total of 139 patients with osteoarthritis or osteonecrosis undergoing OWHTO were enrolled in this prospective, randomized study. Four patients were excluded because of preoperatively diagnosed VTE, and 135 patients were divided into two groups—an edoxaban group and a non-edoxaban group—and underwent computed tomography venography on day 7 to check for postoperative VTE. Blood samples were taken on the day before OWHTO and on postoperative days 1, 3, 7, and 14.


Treatment with edoxaban reduced the incidence of VTE after OWHTO; however, there was no statistically significant difference between the two groups. No major bleeding was noted in the edoxaban group. There were significant differences in the D-dimer level, prothrombin time, fibrinogen level, and thrombin antithrombin complex levels between the groups.


Edoxaban is an oral, once-daily, selective, direct factor Xa inhibitor that is safe and easy to handle. It may offer a new option for preventing VTE after OWHTO.

Level of evidence


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

Fig. 1
Fig. 2


  1. 1.

    Abelseth G, Buckley RE, Pineo GE, Hull R, Rose MS (1996) Incidence of deep-vein thrombosis in patients with fractures of the lower extremity distal to the hip. J Orthop Trauma 10:230–235

  2. 2.

    Bauersachs RM (2012) Clinical presentation of deep vein thrombosis and pulmonary embolism. Best Pract Res Clin Haematol 25:243–251

  3. 3.

    Brosset T, Pasquier G, Migaud H, Gougeon F (2011) Opening wedge high tibial osteotomy performed without filling the defect but with locking plate fixation (TomoFixTM) and early weight-bearing: prospective evaluation of bone union, precision and maintenance of correction in 51 cases. Orthop Traumatol Surg Res 97:705–711

  4. 4.

    Duivenvoorden T, van Diggele P, Reijman M, Bos PK, van Egmond J, Bierma-Zeinstra SMA, Verhaar JAN (2015) Adverse events and survival after closing- and opening-wedge high tibial osteotomy: a comparative study of 412 patients. Knee Surg Sports Traumatol Arthrosc. doi:10.1007/s00167-015-3644-2

  5. 5.

    Fuji T, Fujita S, Tachibana S, Kawai Y (2010) A dose-ranging study evaluating the oral factor Xa inhibitor edoxaban for the prevention of venous thromboembolism in patients undergoing total knee arthroplasty. J Thromb Haemost 8:2458–2468

  6. 6.

    Fuji T, Fujita S, Kawai Y, Nakamura M, Kimura T, Kiuchi Y, Abe K, Tachibana S (2014) Safety and efficacy of edoxaban in patients undergoing hip fracture surgery. Thromb Res 133:1016–1022

  7. 7.

    Fuji T, Wang CJ, Fujita S, Kawai Y, Kimura T, Tachibana S (2014) Safety and efficacy of edoxaban, an oral factor Xa inhibitor, for thromboprophylaxis after total hip arthroplasty in Japan and Taiwan. J Arthroplasty 29:2439–2446

  8. 8.

    Geerts WH, Pineo GF, Heit JA, Bergqvist D, Lassen MR, Colwell CW, Ray JG (2004) Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 126:338S–400S

  9. 9.

    Geerts WH, Bergqvist D, Pineo GF, Heit JA, Samama CM, Lassen MR, Colwell CW, American College of Chest Physicians (2008) Prevention of venous thromboembolism: American College of Chest Physicians evidence-based clinical practice guidelines (8th edition). Chest 133:381S–453S

  10. 10.

    Goshima K, Sawaguchi T, Sakagoshi D, Shigemoto K, Hatsuchi Y, Akahane M (2015) Age does not affect the clinical and radiological outcomes after open-wedge high tibial osteotomy. Knee Surg Sports Traumatol Arthrosc. doi:10.1007/s00167-015-3847-6

  11. 11.

    Gras J (2011) Edoxaban for the prevention of thromboembolic events after surgery. Drugs today 47:753–761

  12. 12.

    Kawaji H, Ishii M, Tamaki Y, Sasaki K, Takagi M (2012) Edoxaban for prevention of venous thromboembolism after major orthopaedic surgery. Orthop Res Rev 4:53–64

  13. 13.

    Lawrence RC, Felson DT, Helmick CG, Arnold LM, Choi H, Deyo RA, Gabriel S, Hirsch R, Hochberg MC, Hunder GG, Jordan JM, Katz JN, Kremers HM, Wolfe F (2008) Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II. Arthritis Rheum 58:26–35

  14. 14.

    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 21:2611–2617

  15. 15.

    Martin R, Birmingham TB, Willits K, Litchfield R, Lebel ME, Giffin JR (2014) Adverse event rates and classifications in medial opening wedge high tibial osteotomy. Am J Sports Med 42:1118–1126

  16. 16.

    McNamara I, Birmingham TB, Fowler PJ, Giffin JR (2013) High tibial osteotomy: evolution of research and clinical applications—a Canadian experience. Knee Surg Sports Traumatol Arthrosc 21:23–31

  17. 17.

    Miller BS, Downie B, Mc Donough EB, Wojtys EM (2009) Complications after medial opening wedge high tibial osteotomy. Arthroscopy 25:639–646

  18. 18.

    Motycka T, Eggerth G, Landsiedl F (2000) The incidence of thrombosis in high tibial osteotomies with and without the use of a tourniquet. Arch Orthop Trauma Surg 120:157–159

  19. 19.

    Polyzois D, Stavlas P, Polyzois V, Zacharakis N (2006) The oblique high tibial osteotomy technique without bone removal and with rigid blade plate fixation for the treatment of medial osteoarthritis of the varus knee: medium and long-term results. Knee Surg Sports Traumatol Arthrosc 14:940–947

  20. 20.

    Raskob G, Cohen AT, Eriksson BI, Puskas D, Shi M, Bocanegra T, Weitz JI (2010) Oral direct factor Xa inhibition with edoxaban for thromboprophylaxis after elective total hip replacement. Thromb Haemost 104:642–649

  21. 21.

    Saier T, Minzlaff P, Feucht MJ, Lämmle L, Burghoff M, Ihle C, Imhoff AB, Hinterwimmer S (2015) Health-related quality of life after open-wedge high tibial osteotomy. Knee Surg Sports Traumatol Arthrosc. doi:10.1007/s00167-015-3938-4

  22. 22.

    Saito T, Kumagai K, Akamatsu Y, Kobayashi H, Kusayama Y (2014) Five- to ten-year outcome following medial opening-wedge high tibial osteotomy with rigid plate fixation in combination with an artificial bone substitute. Bone Joint J 96-B:339–344

  23. 23.

    Sasaki H, Ishida K, Shibanuma N, Tei K, Tateishi H, Toda A, Yamashiro Y, Matsumoto T, Kuroda R, Kurosaka M (2014) Retrospective comparison of three thromboprophylaxis agents, edoxaban, fondaparinux, and enoxaparin, for preventing venous thromboembolism in total knee arthroplasty. Int Orthop 38:525–529

  24. 24.

    Sikorski JM, Hampson WG, Staddon GE (1981) The natural history and aetiology of deep vein thrombosis after total hip replacement. J Bone Joint Surg Br 63-B:171–177

  25. 25.

    Smith TO, Sexton D, Mitchell P, Hing CB (2011) Opening- or closing- wedged high tibial osteotomy: a meta-analysis of clinical and radiological outcomes. Knee 18:361–368

  26. 26.

    Spahn G (2003) Complications in high tibial (medial opening wedge) osteotomy. Arch Orthop Trauma Surg 124:649–653

  27. 27.

    Takeuchi R, Ishikawa H, Kumagai K, Yamaguchi Y, Chiba N, Akamatsu Y, Saito T (2012) Fractures around the lateral cortical hinge after a medial opening-wedge high tibial osteotomy: a new classification of lateral hinge fracture. Arthroscopy 28:85–94

  28. 28.

    The Hokusai-VTE investigators, Büller HR, Decousus H, Grosso MA, Mercuri M, Middeldorp S, Prins MH, Raskob GE, Schellong SM, Schwocho L, Segers A, Shi M, Verhamme P, Wells P (2013) Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med 369:1406–1415

  29. 29.

    Turner RS, Griffiths H, Heatley FW (1993) The incidence of deep-vein thrombosis after upper tibial osteotomy. J Bone Joint Surg Br 75-B:942–944

  30. 30.

    Warwick D, Friedman RJ, Agnelli G, Gil-Garay E, Johnson K, FitzGerald G, Turibio FM (2007) Insufficient duration of venous thromboembolism prophylaxis after total hip or knee replacement when compared with the time course of thromboembolic events: findings from the Global Orthopaedic Registry. J Bone Joint Surg Br 89-B:799–807

  31. 31.

    Yukizawa Y, Inaba Y, Watanabe S, Yajima S, Kobayashi N, Ishida T, Iwamoto N, Choe H, Saito T (2012) Association between venous thromboembolism and plasma levels of both soluble fibrin and plasminogen- activator inhibitor 1 in 170 patients undergoing total hip arthroplasty. Acta Orthopaedica 83:14–21

Download references

Author information

Correspondence to Hideo Kobayashi.

Ethics declarations

Conflict of interest

The authors have no conflict of interest to report. No funding was received to support the research or data analysis in this article. In addition, we have not received funding from any agency that requires us to deposit a copy of the article in a public access database.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (XLSX 14 kb)

Supplementary material 2 (XLSX 12 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Kobayashi, H., Akamatsu, Y., Kumagai, K. et al. The use of factor Xa inhibitors following opening-wedge high tibial osteotomy for venous thromboembolism prophylaxis. Knee Surg Sports Traumatol Arthrosc 25, 2929–2935 (2017).

Download citation


  • Opening-wedge high tibial osteotomy (OWHTO)
  • Venous thromboembolism (VTE)
  • Deep vein thrombosis (DVT)
  • Pulmonary embolism (PE)
  • Edoxaban