107 – What is the chemoprophylactic agent of choice for patients undergoing simultaneous bilateral total knee arthroplasty (SBTKA)?

107 – What is the chemoprophylactic agent of choice for patients undergoing simultaneous bilateral total knee arthroplasty (SBTKA)?

Graham Goh, Leanne Ludwick, Andrea Baldini.

Response/Recommendation: Patients undergoing SBTKA are at a higher risk of venous thromboembolism (VTE) compared to those undergoing unilateral total knee arthroplasty (TKA).  Chemical prophylaxis should be considered for these patients.

Strength of Recommendation: Limited.

Rationale: A SBTKA is an effective surgical option for patients with bilateral knee osteoarthritis as it imparts several benefits including a decreased cumulative operative time and lower economic burden1–3.  Although SBTKA provides several advantages for the patient, it is associated with a higher rate of complications such as VTE.

A vast body of literature has reported an increased risk of VTE following SBTKA compared to unilateral TKA4–11.  This heightened risk may be the result of increased operative time, blood loss, and longer recovery period associated with the operation.  Current VTE prophylaxis guidelines presented by the American Academy of Orthopaedic Surgeons (AAOS) and American College of Chest Physicians (ACCP) do not provide guidance on the most appropriate prophylactic agent to prescribe to patients undergoing SBTKA12,13.  Consequently, it is common practice for surgeons to prescribe more aggressive anticoagulation for these higher-risk patients.

Although aspirin has shown to be as effective as other chemoprophylactic agents with a more favorable safety profile for patients undergoing TKA14–21, existing studies examined heterogenous cohorts containing both unilateral and bilateral procedures22–24.  Furthermore, other studies compared aspirin with potent anticoagulants only after risk-stratifying patients based on VTE risk, prescribing aspirin only to “low-risk” unilateral TKA and potent anticoagulants to “high-risk” bilateral TKA25,26.  As a result, current literature still lacks consensus regarding the most appropriate VTE prophylactic agent for patients undergoing SBTKA.

Two retrospective studies compared the efficacy of various chemoprophylactic agents for the prevention of VTE following SBTKA27,28.  Goel et al., evaluated the incidence of VTE in patients undergoing SBTKA and compared the efficacy of aspirin and warfarin for VTE prevention27.  Employing a validated VTE risk calculator to control for confounding risk factors, the study found that aspirin was as protective as warfarin for these high-risk patients.  Similarly, Nam et al., compared the efficacy of a multimodal regimen (mobile compression device with aspirin) and warfarin in patients undergoing SBTKA, reporting no symptomatic VTE events in the aspirin cohort compared to one in the warfarin cohort28.

Although it is widely recognized that SBTKA is associated with an increased risk of VTE, current literature lacks robust data evaluating the optimal prophylactic agent for these higher-risk patients.  In the absence of such data, it is the recommendation of this workgroup that chemical prophylaxis, which includes aspirin, should be considered for patients undergoing SBTKA.


1.         Kim Y-H, Choi Y-W, Kim J-S. Simultaneous bilateral sequential total knee replacement is as safe as unilateral total knee replacement. J Bone Joint Surg Br. 2009;91(1):64-68. doi:10.1302/0301-620X.91B1.21320

2.         Memtsoudis SG, Hargett M, Russell LA, et al. Consensus statement from the consensus conference on bilateral total knee arthroplasty group. Clin Orthop Relat Res. 2013;471(8):2649-2657. doi:10.1007/s11999-013-2976-9

3.         March LM, Cross M, Tribe KL, et al. Two knees or not two knees? Patient costs and outcomes following bilateral and unilateral total knee joint replacement surgery for OA. Osteoarthritis Cartilage. 2004;12(5):400-408. doi:10.1016/j.joca.2004.02.002

4.         Masrouha KZ, Hoballah JJ, Tamim HM, Sagherian BH. Comparing the 30-Day Risk of Venous Thromboembolism and Bleeding in Simultaneous Bilateral vs Unilateral Total Knee Arthroplasty. J Arthroplasty. 2018;33(10):3273-3280.e1. doi:10.1016/j.arth.2018.06.002

5.         Zhang Z, Shen B, Yang J, Zhou Z, Kang P, Pei F. Risk factors for venous thromboembolism of total hip arthroplasty and total knee arthroplasty: a systematic review of evidences in ten years. BMC Musculoskelet Disord. 2015;16:24. doi:10.1186/s12891-015-0470-0

6.         Mantilla CB, Horlocker TT, Schroeder DR, Berry DJ, Brown DL. Frequency of myocardial infarction, pulmonary embolism, deep venous thrombosis, and death following primary hip or knee arthroplasty. Anesthesiology. 2002;96(5):1140-1146. doi:10.1097/00000542-200205000-00017

7.         Parvizi J, Huang R, Rezapoor M, Bagheri B, Maltenfort MG. Individualized Risk Model for Venous Thromboembolism After Total Joint Arthroplasty. J Arthroplasty. 2016;31(9 Suppl):180-186. doi:10.1016/j.arth.2016.02.077

8.         Memtsoudis SG, Ma Y, González Della Valle A, et al. Perioperative outcomes after unilateral and bilateral total knee arthroplasty. Anesthesiology. 2009;111(6):1206-1216. doi:10.1097/ALN.0b013e3181bfab7d

9.         Cronin M, Dengler N, Krauss ES, et al. Completion of the Updated Caprini Risk Assessment Model (2013 Version). Clin Appl Thromb Hemost. 2019;25:1076029619838052. doi:10.1177/1076029619838052

10.       Berend ME, Ritter MA, Harty LD, et al. Simultaneous bilateral versus unilateral total hip arthroplasty an outcomes analysis. J Arthroplasty. 2005;20(4):421-426. doi:10.1016/j.arth.2004.09.062

11.       Trojani C, d’Ollonne T, Saragaglia D, et al. One-stage bilateral total hip arthroplasty: functional outcomes and complications in 112 patients. Orthop Traumatol Surg Res. 2012;98(6 Suppl):S120-123. doi:10.1016/j.otsr.2012.06.008

12.       Falck-Ytter Y, Francis CW, Johanson NA, et al. Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e278S-e325S. doi:10.1378/chest.11-2404

13.       Jacobs JJ, Mont MA, Bozic KJ, et al. American Academy of Orthopaedic Surgeons clinical practice guideline on: preventing venous thromboembolic disease in patients undergoing elective hip and knee arthroplasty. J Bone Joint Surg Am. 2012;94(8):746-747. doi:10.2106/JBJS.9408.ebo746

14.       Deirmengian GK, Heller S, Smith EB, Maltenfort M, Chen AF, Parvizi J. Aspirin Can Be Used as Prophylaxis for Prevention of Venous Thromboembolism After Revision Hip and Knee Arthroplasty. J Arthroplasty. 2016;31(10):2237-2240. doi:10.1016/j.arth.2016.03.031

15.       Azboy I, Groff H, Goswami K, Vahedian M, Parvizi J. Low-Dose Aspirin Is Adequate for Venous Thromboembolism Prevention Following Total Joint Arthroplasty: A Systematic Review. J Arthroplasty. 2020;35(3):886-892. doi:10.1016/j.arth.2019.09.043

16.       Matharu GS, Kunutsor SK, Judge A, Blom AW, Whitehouse MR. Clinical Effectiveness and Safety of Aspirin for Venous Thromboembolism Prophylaxis After Total Hip and Knee Replacement: A Systematic Review and Meta-analysis of Randomized Clinical Trials. JAMA Intern Med. 2020;180(3):376-384. doi:10.1001/jamainternmed.2019.6108

17.       Faour M, Piuzzi NS, Brigati DP, et al. Low-Dose Aspirin Is Safe and Effective for Venous Thromboembolism Prophylaxis Following Total Knee Arthroplasty. J Arthroplasty. 2018;33(7S):S131-S135. doi:10.1016/j.arth.2018.03.001

18.       Raphael IJ, Tischler EH, Huang R, Rothman RH, Hozack WJ, Parvizi J. Aspirin: an alternative for pulmonary embolism prophylaxis after arthroplasty? Clin Orthop Relat Res. 2014;472(2):482-488. doi:10.1007/s11999-013-3135-z

19.       Bala A, Huddleston JI, Goodman SB, Maloney WJ, Amanatullah DF. Venous Thromboembolism Prophylaxis After TKA: Aspirin, Warfarin, Enoxaparin, or Factor Xa Inhibitors? Clin Orthop Relat Res. 2017;475(9):2205-2213. doi:10.1007/s11999-017-5394-6

20.       Huang R, Buckley PS, Scott B, Parvizi J, Purtill JJ. Administration of Aspirin as a Prophylaxis Agent Against Venous Thromboembolism Results in Lower Incidence of Periprosthetic Joint Infection. J Arthroplasty. 2015;30(9 Suppl):39-41. doi:10.1016/j.arth.2015.07.001

21.       An VVG, Phan K, Levy YD, Bruce WJM. Aspirin as Thromboprophylaxis in Hip and Knee Arthroplasty: A Systematic Review and Meta-Analysis. J Arthroplasty. 2016;31(11):2608-2616. doi:10.1016/j.arth.2016.04.004

22.       Odeh K, Doran J, Yu S, Bolz N, Bosco J, Iorio R. Risk-Stratified Venous Thromboembolism Prophylaxis After Total Joint Arthroplasty: Aspirin and Sequential Pneumatic Compression Devices vs Aggressive Chemoprophylaxis. J Arthroplasty. 2016;31(9 Suppl):78-82. doi:10.1016/j.arth.2016.01.065

23.       Lachiewicz PF, Soileau ES. Mechanical calf compression and aspirin prophylaxis for total knee arthroplasty. Clin Orthop Relat Res. 2007;464:61-64. doi:10.1097/BLO.0b013e3181468951

24.       Intermountain Joint Replacement Center Writing Committee. A prospective comparison of warfarin to aspirin for thromboprophylaxis in total hip and total knee arthroplasty. J Arthroplasty. 2012;27(1):1-9.e2. doi:10.1016/j.arth.2011.03.032

25.       Vulcano E, Gesell M, Esposito A, Ma Y, Memtsoudis SG, Gonzalez Della Valle A. Aspirin for elective hip and knee arthroplasty: a multimodal thromboprophylaxis protocol. Int Orthop. 2012;36(10):1995-2002. doi:10.1007/s00264-012-1588-4

26.       Callaghan JJ, Warth LC, Hoballah JJ, Liu SS, Wells CW. Evaluation of deep venous thrombosis prophylaxis in low-risk patients undergoing total knee arthroplasty. J Arthroplasty. 2008;23(6 Suppl 1):20-24. doi:10.1016/j.arth.2008.05.018

27.       Goel R, Fleischman AN, Tan T, et al. Venous thromboembolic prophylaxis after simultaneous bilateral total knee arthroplasty: aspirin versus warfarin. Bone Joint J. 2018;100-B(1 Supple A):68-75. doi:10.1302/0301-620X.100B1.BJJ-2017-0587.R1

28.       Nam D, Nunley RM, Johnson SR, Keeney JA, Barrack RL. Mobile compression devices and aspirin for VTE prophylaxis following simultaneous bilateral total knee arthroplasty. J Arthroplasty. 2015;30(3):447-450. doi:10.1016/j.arth.2014.10.018

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