113 – What is the optimal choice for VTE prophylaxis following two-stage or resection arthroplasty for treatment of knee and hip periprosthetic joint infection?

113 – What is the optimal choice for VTE prophylaxis following two-stage or resection arthroplasty for treatment of knee and hip periprosthetic joint infection?

Kenneth L. Urish, Mark J. Spangehl. William M. Mihalko.

Response/Recommendation: Following explantation or reimplantation of components as part of a two-stage procedure or definitive resection arthroplasty for a hip or knee periprosthetic joint infection (PJI), patients should be stratified based on the risk of venous thromboembolism (VTE) events vs. the risk of post-operative complications associated with anticoagulation. Anticoagulation can be selected from established guidelines for primary total hip arthroplasty (THA) and total knee arthroplasty (TKA).

Strength of Recommendation: Moderate.

Rationale: There are minimal clinical studies that directly focus on the risk and incidence of VTE during the treatment of PJI. There are a number of retrospective clinical studies comparing the incidence of VTE events between primary and revision arthroplasty surgery seeking to identify associated independent risk factors. Compared to primary arthroplasty, revision surgery has increased clinical concern for VTE events given the increased surgical exposure, surgical duration, and restricted weight-bearing and mobilization post-operatively. However, the available clinical evidence suggests that revision surgery is not an independent risk factor for VTE, anticoagulation can be associated with post-operative complications, and that aspirin (ASA) can be non-inferior to other classes of anticoagulation when patients are appropriately selected. Combined, the limited available evidence suggests that patients should be stratified based on risk for thromboembolic events vs. the risk of post-operative complications associated with anticoagulation, and that this can then be selected from established guidelines for primary THA and TKA in patients being treated with a two-stage exchange or resection arthroplasty.

Predictors of VTE Events in Revision Arthroplasty Knee and Hip Surgery: Multiple studies have compared the incidence of VTE in primary and revision THA and TKA. Comparing direct VTE rates between revision and primary arthroplasty surgery, some studies have observed no difference in VTE rates1-4, some have observed a decreased incidence1, and others have observed an increased incidence5-7. In the studies that observed a higher incidence of VTE in revision vs. primary arthroplasty surgery, when the rates were adjusted for risk factors and comorbidities, revision surgery was either not associated with a higher risk of VTE5, or had a lower difference based on risk stratification8. Only one of these studies, after adjusting for risk, still observed revision surgery as an independent factor for increased VTE. The combined evidence suggests that revision arthroplasty surgery is not an independent risk factor for VTE.

These studies also assessed independent risk factors of VTE in revision surgery. In a registry study of the National Surgical Quality Improvement Program (NSQIP), independent risk factors for deep venous thrombosis (DVT) were age > 70 years, malnutrition, infection, operating time > 3 hours, American Society of Anesthesiologist score > 4, kidney disease, and race. Independent risk factors for pulmonary embolism (PE) were age > 70 years, operating time > 3 hours, and race5. This was the only study in the literature that identified surgical infection as an independent risk factor of VTE with an odds ratio 4.15. A separate retrospective institutional study identified independent VTE risk factors: body mass index (BMI) > 25kg/m2, knee procedure, Charlson comorbidity index (CCI) > 2, chronic obstructive pulmonary disease (COPD), anemia, DVT, atrial fibrillation, and depression2. A multicenter retrospective study, in a high-risk group for VTE events, identified independent predictors for VTE, including a previous history of VTE, metastatic cancer, myeloproliferative disorder, transfusion, peripheral vascular disease, and age1. It should be emphasized that these are studies and not guidelines.

Restricted weight-bearing and limited mobility remains a unique risk factor for VTE events following revision as compared to primary THA and TKA surgery. Early mobilization, when clinically appropriate, remains a key tenant in orthopaedic fracture care and arthroplasty for preventing VTE events. In large part because of the unacceptable ethical concerns in conducting the clinical studies, there is minimal literature that can directly assess if weight-bearing restrictions are an independent predictor of VTE in fracture care and management. Nevertheless, there is strong consensus in orthopaedic surgery that early mobilization and weight-bearing are important at limiting VTE events. In non-operative fractures, literature from emergency medicine suggests that immobilization combined with non-weight-bearing are a risk factor for VTE events, but the quality of the evidence is low9,10. In orthopaedic trauma, limited evidence suggests that weight-bearing status is not a predictor of VTE events with fracture fixation11,12.

VTE Prophylaxis in Revision THA and TKA: The use of aggressive anticoagulation in the prevention of VTE is associated with adverse events and does not have a benign safety profile. The incidence of VTE in arthroplasty surgery is well-established, but increased bleeding is associated with its own post-operative complications13-15. Revision procedures are associated with increased post-operative bleeding complications4, potentially leading to poorer outcomes as revision arthroplasty is associated with higher rates of complications, especially infection3. A series of studies provide compelling evidence that reducing complications associated with bleeding reduces rates of PJI1,16,17. When patients were given more aggressive anticoagulation regardless of VTE or bleeding risk, the incidence of post-operative wound complications increased with no change in overall VTE rates as compared to when a more nuanced approach was utilized that risk-stratified patients18.

ASA has an increased safety profile, and available evidence suggests it is non-inferior to other more aggressive anticoagulation. In revision arthroplasty surgery, the use of ASA had no difference in VTE rates as compared to other anticoagulants19. In an institutional registry that compared warfarin and ASA, no difference was observed in VTE rates, and warfarin was an independent predictor of mortality and PJI20.

Based on these concerns, the American Academy of Orthopaedic Surgery (AAOS) recommends stratification of VTE risk balanced with risks associated with bleeding complications from anticoagulation21. The AAOS clinical practice guidelines (CPG) on VTE prophylaxis recommended early mobilization as a consensus recommendation for high-risk for VTE patients and those with a history of VTE. Furthermore, there was a consensus recommendation to consider both mechanical and pharmacologic treatment after surgery. In comparison, the previous American College of Chest Physicians (ACCP) guidelines recommend more aggressive prophylaxis with low-molecular-weight heparin (LMWH) or direct oral anticoagulants22. As discussed above, there is published evidence that ACCP guidelines with warfarin in particular lead to higher complication rates18. More recently, the ACCP guidelines have included the use of low-dose ASA based on non-inferiority clinical studies to other anticoagulants in primary arthroplasty patients23. Surgeons should consider the guidelines for prophylaxis after hip and knee arthroplasty as recommended by the AAOS21 and the ACCP22 as well as information on stratification of risk discussed by the 2020 International Consensus on VTE [REFERNCE APPROPRIATE CHAPTER IN JBJS].

Without direct evidence in the literature regarding the optimum VTE prophylaxis strategy for this patient group, one should consider that revision surgery is not an independent risk factor for VTE, that aggressive anticoagulation has potential adverse events, that low dose ASA is non-inferior in the appropriate patient population, and the need to stratify VTE and bleeding risk factors when selecting anticoagulation agents for two-stage exchange and resection arthroplasty as per the AAOS21 and the ACCP22 guidelines with further information on stratification of risk discussed by the 2020 International Consensus on VTE [REFERNCE APPROPRIATE CHAPTER IN JBJS].


1. Tan TL, Foltz C, Huang R, Chen AF, Higuera C, Siqueira M, Hansen EN, Sing DC, Parvizi J. Potent Anticoagulation Does Not Reduce Venous Thromboembolism in High-Risk Patients. J Bone Joint Surg Am 101(7): 589, 2019

2. Parvizi J, Huang R, Raphael IJ, Arnold WV, Rothman RH. Symptomatic pulmonary embolus after joint arthroplasty: stratification of risk factors. Clin Orthop Relat Res 472(3): 903, 2014

3. Bohl DD, Samuel AM, Basques BA, Della Valle CJ, Levine BR, Grauer JN. How Much Do Adverse Event Rates Differ Between Primary and Revision Total Joint Arthroplasty? J Arthroplasty 31(3): 596, 2016

4. Bautista M, Muskus M, Tafur D, Bonilla G, Llinas A, Monsalvo D. Thromboprophylaxis for Hip Revision Arthroplasty: Can We Use the Recommendations for Primary Hip Surgery? A Cohort Study. Clin Appl Thromb Hemost 25: 1076029618820167, 2019

5. Courtney PM, Boniello AJ, Levine BR, Sheth NP, Paprosky WG. Are Revision Hip Arthroplasty Patients at Higher Risk for Venous Thromboembolic Events Than Primary Hip Arthroplasty Patients? J Arthroplasty 32(12): 3752, 2017

6. Shahi A, Chen AF, Tan TL, Maltenfort MG, Kucukdurmaz F, Parvizi J. The Incidence and Economic Burden of In-Hospital Venous Thromboembolism in the United States. J Arthroplasty 32(4): 1063, 2017

7. Ramjeesingh M, Gaarn A, Rothstein A. The locations of the three cysteine residues in the primary structure of the intrinsic segments of band 3 protein, and implications concerning the arrangement of band 3 protein in the bilayer. Biochim Biophys Acta 729(1): 150, 1983

8. Boylan MR, Perfetti DC, Kapadia BH, Delanois RE, Paulino CB, Mont MA. Venous Thromboembolic Disease in Revision vs Primary Total Knee Arthroplasty. J Arthroplasty 32(6): 1996, 2017

9. Riou B, Rothmann C, Lecoules N, Bouvat E, Bosson JL, Ravaud P, Samama CM, Hamadouche M. Incidence and risk factors for venous thromboembolism in patients with nonsurgical isolated lower limb injuries. Am J Emerg Med 25(5): 502, 2007

10. Horner D. Towards evidence-based emergency medicine: best BETs from the Manchester Royal Infirmary. Evidence exists to guide thromboembolic prophylaxis in ambulatory patients with temporary lower limb immobilisation. Emerg Med J 28(8): 718, 2011

11. Vollans S, Chaturvedi A, Sivasankaran K, Madhu T, Hadland Y, Allgar V, Sharma HK. Symptomatic venous thromboembolism following circular frame treatment for tibial fractures. Injury 46(6): 1108, 2015

12. Tu DP, Liu Z, Yu YK, Xu C, Shi XL. Internal Fixation versus Hemiarthroplasty in the Treatment of Unstable Intertrochanteric Fractures in the Elderly: A Systematic Review and Meta-Analysis. Orthop Surg 12(4): 1053, 2020

13. Sachs RA, Smith JH, Kuney M, Paxton L. Does anticoagulation do more harm than good?: A comparison of patients treated without prophylaxis and patients treated with low-dose warfarin after total knee arthroplasty. J Arthroplasty 18(4): 389, 2003

14. Patel VP, Walsh M, Sehgal B, Preston C, DeWal H, Di Cesare PE. Factors associated with prolonged wound drainage after primary total hip and knee arthroplasty. J Bone Joint Surg Am 89(1): 33, 2007

15. Drain NP, Gobao VC, Bertolini DM, Smith C, Shah NB, Rothenberger SD, Dombrowski ME, O’Malley MJ, Klatt BA, Hamlin BR, Urish KL. Administration of Tranexamic Acid Improves Long-Term Outcomes in Total Knee Arthroplasty. J Arthroplasty 35(6S): S201, 2020

16. Parvizi J, Ghanem E, Joshi A, Sharkey PF, Hozack WJ, Rothman RH. Does “excessive” anticoagulation predispose to periprosthetic infection? J Arthroplasty 22(6 Suppl 2): 24, 2007

17. Hughes LD, Lum J, Mahfoud Z, Malik RA, Anand A, Charalambous CP. Comparison of Surgical Site Infection Risk Between Warfarin, LMWH, and Aspirin for Venous Thromboprophylaxis in TKA or THA: A Systematic Review and Meta-Analysis. JBJS Rev 8(12): e20 00021, 2020

18. Novicoff WM, Brown TE, Cui Q, Mihalko WM, Slone HS, Saleh KJ. Mandated venous thromboembolism prophylaxis: possible adverse outcomes. J Arthroplasty 23(6 Suppl 1): 15, 2008

19. 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 31(10): 2237, 2016

20. Huang RC, Parvizi J, Hozack WJ, Chen AF, Austin MS. Aspirin Is as Effective as and Safer Than Warfarin for Patients at Higher Risk of Venous Thromboembolism Undergoing Total Joint Arthroplasty. J Arthroplasty 31(9 Suppl): 83, 2016

21. Jacobs JJ, Mont MA, Bozic KJ, Della Valle CJ, Goodman SB, Lewis CG, Yates AC, Jr., Boggio LN, Watters WC, 3rd, Turkelson CM, Wies JL, Sluka P, Hitchcock K. 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 94(8): 746, 2012

22. Falck-Ytter Y, Francis CW, Johanson NA, Curley C, Dahl OE, Schulman S, Ortel TL, Pauker SG, Colwell CW, Jr. 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 141(2 Suppl): e278S, 2012

23. Tang A, Zak SG, Waren D, Iorio R, Slover JD, Bosco JA, Schwarzkopf R. Low-Dose Aspirin is Safe and Effective for Venous Thromboembolism Prevention in Patients Undergoing Revision Total Knee Arthroplasty: A Retrospective Cohort Study. J Knee Surg, 2020

Leave a Reply

This site uses Akismet to reduce spam. Learn how your comment data is processed.

%d bloggers like this: