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 rates^1-4, some have observed a decreased incidence¹, and others have observed an increased incidence^5-7. 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 low^9,10. In orthopaedic trauma, limited evidence suggests that weight-bearing status is not a predictor of VTE events with fracture fixation^11,12.

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 complications^13-15. 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 PJI^1,16,17. 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].

References:

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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

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