114 – Should the method for VTE prophylaxis be altered in patients undergoing revision for infection?

114 – Should the method for VTE prophylaxis be altered in patients undergoing revision for infection?

Karan Goswami, P. Maxwell Courtney, Ran Schwarzkopf, Mohammad Al Mutani, Stephen Silva, Gwo-Chin Lee.

Response/Recommendation: Although infection is known to increase the risk of venous thromboembolism (VTE), there is no evidence to support a change in the approach to this group of patients. In general, aspirin (ASA) is safe and effective in revision surgery. Nevertheless, more potent anticoagulation strategies should be considered in the high-risk cases after risk stratification as determined by the American Academy of Orthopaedic Surgeons (AAOS) and the American College of Chest Physicians (ACCP) guidelines and by further information found for question xxx.

Strength of Recommendation: Limited.

Rationale: Patients undergoing revision arthroplasty surgery have been shown to have higher rates of VTE when compared to primary arthroplasty1. However, revision alone is not considered an independent risk factor for VTE2–4. Variables such as infection, prolonged operative time, and decreased post-operative mobilization have been shown to increase the risk of VTE. Revision arthroplasty due to periprosthetic joint infection (PJI) is complex and challenging to manage, and much effort has been made to minimize its associated complications.

PJI is a rare, but devastating, complication of total joint arthroplasty (TJA) that place a significant burden on both patients and health care systems. The incidence of PJI ranges from 1-2% in primary arthroplasty5. Data collected from joint registries demonstrates an overall weighted mean of 0.97% for total hip arthroplasty (THA) and 1.03% for total knee arthroplasty (TKA). The rate of revision due to PJI has increased by two-fold for primary THA and three-fold for revision THA6. Infection has been shown to be an independent risk factor for VTE7. A recent study demonstrated that the odds of developing VTE were more than double for revision TKA compared to aseptic revisions8. These findings suggest that the indication for septic revision arthroplasty should be considered when selecting post-operative VTE prophylaxis.

There are currently no specific guidelines addressing thromboprophylaxis for revision arthroplasty, and the current recommendations are extrapolated from primary arthroplasty procedures. In addition, many clinical trials have excluded revision arthroplasty when evaluating the efficacy and safety of anticoagulation modalities. Clinical apprehension of increased rates of VTE in revision arthroplasty stem from a more extensive and complex surgical exposure, longer operative times, larger systemic inflammatory response, and decreased post-operative mobilization. However, utilization of a more aggressive thromboprophylaxis regimen following revision arthroplasty could lead to poorer outcomes, as revision arthroplasty has been associated with increased rates of bleeding and complications9. Therefore, the decision of postoperative anticoagulation must weigh the risk of post-operative bleeding with that of VTE.

Traditionally, more potent anticoagulants such as vitamin K antagonists (warfarin), low-molecular-weight heparin (LMWH), or direct-oral anticoagulants (DOAC) have been reserved for higher-risk patients with established risk factors including obesity or prior history of VTE10–13. In the setting of PJI, patients undergoing revision arthroplasty are receiving antibiotics that have been shown to disrupt the gastrointestinal microbiome14. These antibiotics can harm the vitamin-K producing gut flora causing agents like warfarin to be associated with supratherapeutic international normalized ratios (INR) and increased bleeding. Additionally, LMWH and DOAC have high potency and fast onset but have been associated with higher rates of post-operative wound drainage15.

In recent years, significant attention has been turned to using less potent antithrombotic agents such as ASA in both primary and revision arthroplasties. In a large retrospective study that looked at 2,997 patients, Deirmengian et al., evaluated whether ASA was as effective as warfarin for VTE prophylaxis in revision arthroplasty. They found a significantly higher incidence of symptomatic VTE in the warfarin group (1.75%) compared with the ASA group (0.56%). All other complication rates were similar except for the rate of bleeding events, which was also higher with the administration of warfarin. A limitation of the study included an analysis of confounders which revealed that patients in the warfarin group had higher rates of revision for PJI, higher Charlson comorbidity index scores, and longer procedural times.

Another recent retrospective study by Manista et al., analyzed various VTE prophylaxis regimens in 1,917 low-risk patients who underwent revision arthroplasty2. They found that the most commonly used prophylactic agent was rivaroxaban (40.6%), followed by warfarin (28.5%), and ASA (27.6%). There was no statistically significant difference in post-operative VTE or complications observed. They concluded that ASA was just as effective as the other agents without the increased risk of bleeding in low-risk patients.

There has also been a trend towards using a lower dose ASA for VTE prophylaxis in revision arthroplasty compared to the traditional higher doses used in earlier regimens. Three retrospective studies within the past two years have cited low-dose ASA as a suitable chemoprophylactic agent in revision arthroplasty16–18. Tang et al., compared a prophylaxis protocol of 81 mg of ASA twice a day (bis in die [BID]) compared to 325 mg ASA BID in 1,361 revision THA patients and found no difference in total VTE, bleeding, or any other complication between the two groups16. A similar retrospective study was conducted for patients undergoing revision TKA and also observed no significant difference between low- and high-dose ASA for total VTE, bleeding, or any other complications17. Finally, Tang et al., reviewed the efficacy and safety of low-dose ASA in higher-risk patients undergoing revision arthroplasty18. As prior studies have suggested that obesity may be associated with an increased risk of VTE, wound complications, and infections, these patients are routinely classified as high-risk and therefore traditionally prescribed a higher dose of ASA for prophylaxis. However, in their study, they found no difference in VTE rates or any other complications using low-dose ASA and observed similar complication rates to non-obese patients.

The management of revision arthroplasty in the setting of PJI is variable and challenging due to its complex nature. Patients with PJI represent a group at elevated risk for VTE following revision arthroplasty and these factors should be considered when tailoring VTE prophylaxis. Due to the lack of current evidence, it is difficult to recommend a specific VTE prophylaxis or any alterations to existing regimens. While there is data supporting ASA as a suitable thromboprophylaxis for most patients, patients at much higher risk of VTE may require a more potent agent. However, there is recent literature to suggest that low-dose ASA may be safe for higher-risk patients undergoing septic revision arthroplasty and is non-inferior at maintaining low rates of VTE. Further research is warranted to identify higher-risk patients, stratify risk factors, and determine whether modifications to VTE prophylaxis are required. Future prospective studies should address the optimal approach to VTE prophylaxis in this high-risk population.


1.         Santana DC, Emara AK, Orr MN, et al. An Update on Venous Thromboembolism Rates and Prophylaxis in Hip and Knee Arthroplasty in 2020. Medicina (Mex). 2020;56(9):416. doi:10.3390/medicina56090416

2.         Manista GC, Batko BD, Sexton AC, et al. Anticoagulation in Revision Total Joint Arthroplasty: A Retrospective Review of 1917 Cases. Orthopedics. 2019;42(6):323-329. doi:10.3928/01477447-20190906-02

3.         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. 2017;32(12):3752-3756. doi:10.1016/j.arth.2017.07.028

4.         Wakabayashi H, Hasegawa M, Niimi R, Sudo A. Clinical analysis of preoperative deep vein thrombosis risk factors in patients undergoing total hip arthroplasty. Thromb Res. 2015;136(5):855-858. doi:10.1016/j.thromres.2015.06.021

5.         Ahmed SS, Haddad FS. Prosthetic joint infection. Bone Jt Res. 2019;8(11):570-572. doi:10.1302/2046-3758.812.BJR-2019-0340

6.         Lenguerrand E, Whitehouse MR, Beswick AD, Jones SA, Porter ML, Blom AW. Revision for prosthetic joint infection following hip arthroplasty: Evidence from the National Joint Registry. Bone Jt Res. 2017;6(6):391-398. doi:10.1302/2046-3758.66.BJR-2017-0003.R1

7.         Cohoon KP, Ashrani AA, Crusan DJ, Petterson TM, Bailey KR, Heit JA. Is Infection an Independent Risk Factor for Venous Thromboembolism? A Population-Based, Case-Control Study. Am J Med. 2018;131(3):307-316.e2. doi:10.1016/j.amjmed.2017.09.015

8.         Bass AR, Zhang Y, Mehta B, et al. Periprosthetic Joint Infection Is Associated with an Increased Risk of Venous Thromboembolism Following Revision Total Knee Replacement: An Analysis of Administrative Discharge Data. J Bone Joint Surg Am. 2021;103(14):1312-1318. doi:10.2106/JBJS.20.01486

9.         Kester BS, Merkow RP, Ju MH, et al. Effect of post-discharge venous thromboembolism on hospital quality comparisons following hip and knee arthroplasty. J Bone Joint Surg Am. 2014;96(17):1476-1484. doi:10.2106/JBJS.M.01248

10.       Allen D, Sale G. Lower limb joint replacement in patients with a history of venous thromboembolism. Bone Jt J. 2014;96-B(11):1515-1519. doi:10.1302/0301-620X.96B11.33492

11.       Brown GA. Venous thromboembolism prophylaxis after major orthopaedic surgery: a pooled analysis of randomized controlled trials. J Arthroplasty. 2009;24(6 Suppl):77-83. doi:10.1016/j.arth.2009.06.002

12.       Nam D, Nunley RM, Johnson SR, Keeney JA, Clohisy JC, Barrack RL. The Effectiveness of a Risk Stratification Protocol for Thromboembolism Prophylaxis After Hip and Knee Arthroplasty. J Arthroplasty. 2016;31(6):1299-1306. doi:10.1016/j.arth.2015.12.007

13.       Kapoor A, Ellis A, Shaffer N, et al. Comparative effectiveness of venous thromboembolism prophylaxis options for the patient undergoing total hip and knee replacement: a network meta-analysis. J Thromb Haemost JTH. 2017;15(2):284-294. doi:10.1111/jth.13566

14.       Baillargeon J, Holmes HM, Lin Y-L, Raji MA, Sharma G, Kuo Y-F. Concurrent use of warfarin and antibiotics and the risk of bleeding in older adults. Am J Med. 2012;125(2):183-189. doi:10.1016/j.amjmed.2011.08.014

15.       Turpie AGG, Haas S, Kreutz R, et al. A non-interventional comparison of rivaroxaban with standard of care for thromboprophylaxis after major orthopaedic surgery in 17,701 patients with propensity score adjustment. Thromb Haemost. 2014;111(1):94-102. doi:10.1160/TH13-08-0666

16.       Tang A, Zak S, Iorio R, Slover J, Bosco J, Schwarzkopf R. Low-Dose Aspirin Is Safe and Effective for Venous Thromboembolism Prevention in Patients Undergoing Revision Total Hip Arthroplasty: A Retrospective Cohort Study. J Arthroplasty. 2020;35(8):2182-2187. doi:10.1016/j.arth.2020.03.040

17.       Tang A, Zak SG, Waren D, et al. 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. Published online September 8, 2020. doi:10.1055/s-0040-1716377

18.       Tang A, Sicat CS, Singh V, Rozell JC, Schwarzkopf R, Long WJ. Aspirin Use for Venous Thromboembolism Prevention Is Safe and Effective in Overweight and Obese Patients Undergoing Revision Total Hip and Knee Arthroplasty. J Arthroplasty. 2021;36(7S):S337-S344. doi:10.1016/j.arth.2020.12.006

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