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.
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