Aspirin Administered for Venous Thromboembolism Prophylaxis May Protect Against Stiffness Following Total Knee Arthroplasty

Published:January 09, 2022DOI:



      Aspirin has become the main agent for venous thromboembolism (VTE) prophylaxis following total knee arthroplasty (TKA). This study assesed whether aspirin is associated with less knee stiffness compared to warfarin and other chemoprophylaxis agents.


      This was a retrospective review of all primary and revision TKA performed between January 2009 and October 2020 at a high volume institution. Demographics, comorbidity data and operative variables were extracted from medical records. VTE prophylaxis administered during this time period included aspirin, warfarin, and “others” (factor Xa, Unfractionated Heparin, low molecular weight heparin, fondaparinux, ADP receptor inhibitor and direct thrombin inhibitor). The primary outcome assessed was manipulation under anesthesia (MUA) performed within 6 months of index surgery. Secondary outcome included major bleeding events (MBE). Univariate followed by multivariate regression analysis were performed.


      A total of 15,903 cases were included in the study, of which 531 (3.3%) patients developed stiffness that required MUA. The rates of MUA were 2.7% (251/9223) for patients receiving aspirin, 4.2% (238/5709) for patients receiving warfarin and 4.3% (42/971) for all others (p’s<0.001). Multivariate regression analysis confirmed that aspirin is associated with lower rates of VTE compared to warfarin (adjusted odds ratio 1.423. 95% CI 1.158-1.747, p<0.001) and compared to other anticoagulation medications (adjusted odds ratio 1.742, 95% CI 1.122-2.704, p=0.013). MBE were also significantly lower in patients who received aspirin compared to the other 2 groups (p’s=0.001).


      Aspirin prophylaxis is associated with lower rates of MUA following TKA compared to warfarin and other VTE chemoprophylactic agents when grouped together.


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        • Bong M.R.
        • Di Cesare P.E.
        Stiffness after total knee arthroplasty.
        J Am Acad Orthop Surg. 2004; 12: 164-171
        • Gu A.
        • Michalak A.J.
        • Cohen J.S.
        • Almeida N.D.
        • McLawhorn A.S.
        • Sculco P.K.
        Efficacy of Manipulation Under Anesthesia for Stiffness Following Total Knee Arthroplasty: A Systematic Review.
        J Arthroplasty. 2018; 33: 1598-1605
        • Kim J.
        • Nelson C.L.
        • Lotke P.A.
        Stiffness After Total Knee Arthroplasty: Prevalence of the Complication and Outcomes of Revision.
        JBJS. 2004; 86: 1479-1484
        • Yercan H.S.
        • Sugun T.S.
        • Bussiere C.
        • Ait Si Selmi T.
        • Davies A.
        • Neyret P.
        Stiffness after total knee arthroplasty: Prevalence, management and outcomes.
        The Knee. 2006; 13: 111-117
        • Manrique J.
        • Gomez M.M.
        • Parvizi J.
        Stiffness after total knee arthroplasty.
        J Knee Surg. 2015; 28: 119-126
        • Zachwieja E.
        • Perez J.
        • Hardaker W.M.
        • Levine B.
        • Sheth N.
        Manipulation Under Anesthesia and Stiffness After Total Knee Arthroplasty.
        JBJS Reviews. 2018; 6: e2
        • Schiavone Panni A.
        • Cerciello S.
        • Vasso M.
        • Tartarone M.
        Stiffness in total knee arthroplasty.
        J Orthop Traumatol. 2009; 10: 111-118
      1. Factors affecting the range of movement of total knee arthroplasty - PubMed n.d. (accessed August 4, 2021).

        • Werner B.C.
        • Carr J.B.
        • Wiggins J.C.
        • Gwathmey F.W.
        • Browne J.A.
        Manipulation Under Anesthesia After Total Knee Arthroplasty is Associated with An Increased Incidence of Subsequent Revision Surgery.
        J Arthroplasty. 2015; 30: 72-75
        • Pfefferle K.J.
        • Shemory S.T.
        • Dilisio M.F.
        • Fening S.D.
        • Gradisar I.M.
        Risk factors for manipulation after total knee arthroplasty: a pooled electronic health record database study.
        J Arthroplasty. 2014; 29: 2036-2038
        • Plate J.F.
        • Wohler A.D.
        • Brown M.L.
        • Sun D.
        • Fino N.F.
        • Lang J.E.
        Factors Associated with Range of Motion Recovery Following Manipulation Under Anesthesia.
        Surg Technol Int. 2016; 29: 295-301
        • Knapp P.
        • Weishuhn L.
        • Pizzimenti N.
        • Markel D.C.
        Risk factors for manipulation under anaesthesia after total knee arthroplasty.
        The Bone & Joint Journal. 2020; 102-B: 66-72
        • Newman E.T.
        • Herschmiller T.A.
        • Attarian D.E.
        • Vail T.P.
        • Bolognesi M.P.
        • Wellman S.S.
        Risk Factors, Outcomes, and Timing of Manipulation Under Anesthesia After Total Knee Arthroplasty.
        J Arthroplasty. 2018; 33: 245-249
      2. Influence of the posterior tibial slope on the flexion gap in total knee arthroplasty - PubMed n.d. (accessed August 5, 2021).

        • Kahlenberg C.A.
        • Richardson S.S.
        • Schairer W.W.
        • Sculco P.K.
        Type of Anticoagulant Used After Total Knee Arthroplasty Affects the Rate of Knee Manipulation for Postoperative Stiffness.
        J Bone Joint Surg Am. 2018; 100: 1366-1372
        • Walton N.P.
        • Jahromi I.
        • Dobson P.J.
        • Angel K.R.
        • Lewis P.L.
        • Campbell D.G.
        Arthrofibrosis following total knee replacement; does therapeutic warfarin make a difference?.
        Knee. 2005; 12: 103-106
        • Parvizi J.
        • Huang R.
        • Restrepo C.
        • Chen A.F.
        • Austin M.S.
        • Hozack W.J.
        • et al.
        Low-Dose Aspirin Is Effective Chemoprophylaxis Against Clinically Important Venous Thromboembolism Following Total Joint Arthroplasty: A Preliminary Analysis.
        The Journal of Bone and Joint Surgery. 2017; 99: 91-98
        • Azboy I.
        • Barrack R.
        • Thomas A.M.
        • Haddad F.S.
        • Parvizi J.
        Aspirin and the prevention of venous thromboembolism following total joint arthroplasty: commonly asked questions.
        The Bone & Joint Journal. 2017; 99-B: 1420-1430
        • An V.V.G.
        • Phan K.
        • Levy Y.D.
        • Bruce W.J.M.
        Aspirin as Thromboprophylaxis in Hip and Knee Arthroplasty: A Systematic Review and Meta-Analysis.
        The Journal of Arthroplasty. 2016; 31: 2608-2616
        • Faour M.
        • Piuzzi N.S.
        • Brigati D.P.
        • Klika A.K.
        • Mont M.A.
        • Barsoum W.K.
        • et al.
        Low-Dose Aspirin Is Safe and Effective for Venous Thromboembolism Prophylaxis Following Total Knee Arthroplasty.
        The Journal of Arthroplasty. 2018; 33: S131-S135
        • Singh V.
        • Shahi A.
        • Saleh U.
        • Tarabichi S.
        • Oliashirazi A.
        Persistent Wound Drainage among Total Joint Arthroplasty Patients Receiving Aspirin vs Coumadin.
        The Journal of Arthroplasty. 2020; 35: 3743-3746
      3. Administration of Aspirin as a Prophylaxis Agent Against Venous Thromboembolism Results in Lower Incidence of Periprosthetic Joint Infection - PubMed n.d. (accessed August 6, 2021).

        • Usher K.M.
        • Zhu S.
        • Mavropalias G.
        • Carrino J.A.
        • Zhao J.
        • Xu J.
        Pathological mechanisms and therapeutic outlooks for arthrofibrosis.
        Bone Research. 2019; 7: 1-24
        • Wang Y.
        • He G.
        • Tang H.
        • Shi Y.
        • Kang X.
        • Lyu J.
        • et al.
        Aspirin inhibits inflammation and scar formation in the injury tendon healing through regulating JNK/STAT‐3 signalling pathway.
        Cell Prolif. 2019; 52
        • Yu T.-H.
        • Chou Y.-Y.
        • Tung Y.-C.
        Should we pay attention to surgeon or hospital volume in total knee arthroplasty? Evidence from a nationwide population-based study.
        PLOS ONE. 2019; 14e0216667
        • Parvizi J.
        • Huang R.
        • Rezapoor M.
        • Bagheri B.
        • Maltenfort M.G.
        Individualized Risk Model for Venous Thromboembolism After Total Joint Arthroplasty.
        J Arthroplasty. 2016; 31: 180-186
        • Schulman S.
        • Angerås U.
        • Bergqvist D.
        • Eriksson B.
        • Lassen M.R.
        • Fisher W.
        • et al.
        Definition of major bleeding in clinical investigations of antihemostatic medicinal products in surgical patients.
        J Thromb Haemost. 2010; 8: 202-204
        • Desai A.S.
        • Karmegam A.
        • Dramis A.
        • Board T.N.
        • Raut V.
        Manipulation for stiffness following total knee arthroplasty: when and how often to do it?.
        Eur J Orthop Surg Traumatol. 2014; 24: 1291-1295
        • Vane J.R.
        • Botting R.M.
        The mechanism of action of aspirin.
        Thromb Res. 2003; 110: 255-258
        • Parvizi J.
        • Tarity T.D.
        • Steinbeck M.J.
        • Politi R.G.
        • Joshi A.
        • Purtill J.J.
        • et al.
        Management of stiffness following total knee arthroplasty.
        J Bone Joint Surg Am. 2006; 88: 175-181
      4. Management of arthrofibrosis in haemophilic arthropathy - PubMed n.d. (accessed August 9, 2021).

      5. Causes of Aseptic Persistent Pain after Total Knee Arthroplasty - PubMed n.d. (accessed August 9, 2021).

      6. Patients’ expectations of knee surgery - PubMed n.d. (accessed August 9, 2021).

      7. Postoperative Stiffness Requiring Manipulation Under Anesthesia Is Significantly Reduced After Simultaneous Versus Staged Bilateral Total Knee Arthroplasty - PubMed n.d. (accessed August 9, 2021).

      8. Functional outcomes of simultaneous bilateral versus unilateral total knee arthroplasty - PubMed n.d. (accessed August 9, 2021).

      9. Gait after unilateral total knee arthroplasty: frontal plane analysis - PubMed n.d. (accessed August 9, 2021).

      10. Total knee arthroplasty in patients with poliomyelitis - PubMed n.d. (accessed August 9, 2021).

      11. Knee-attributable medical costs and risk of re-surgery among patients utilizing non-surgical treatment options for knee arthrofibrosis in a managed care population - PubMed n.d. (accessed August 9, 2021).