The 2022 International Consensus Meeting (ICM) on venous thromboembolism (VTE) in Hip and Knee strongly recommends low-dose aspirin (ASA) as the primary method of VTE prophylaxis for all patients undergoing total joint arthroplasty (TJA), including those at moderate to high risk. For simultaneous bilateral total knee arthroplasty (TKA) or total hip arthroplasty (THA), chemoprophylaxis should be considered given the increased VTE risk, although the optimal agent for bilateral THA remains uncertain. The consensus does not specify a preferred aspirin dose; however the supporting studies evaluated doses of 81 mg, 100 mg, and 325 mg in patients undergoing THA and/or TKA. The ICM also reports that aspirin is associated with lower bleeding rates and lower 30-day readmission rates than several more potent anticoagulants, although differences in patient risk profiles may confound these comparisons. Evidence suggests aspirin is associated with similar or lower surgical site and periprosthetic joint infection rates compared with more potent agents, particularly vitamin K antagonists. For revision arthroplasty, including procedures involving periprosthetic joint infection, aspirin remains a reasonable option; however, patients should be risk-stratified, with more potent anticoagulation considered when VTE risk is elevated. [1]
In trauma, the ICM identifies low-molecular-weight heparin (LMWH) as the preferred prophylactic agent for patients with multiple orthopedic injuries. However, aspirin is recognized as an effective option for VTE prophylaxis in patients undergoing hip fracture fixation or arthroplasty, as well as selected patients with nonoperatively managed hip fractures. For hip fracture surgery, mechanical and pharmacological prophylaxis are recommended following individualized risk assessment, with prophylaxis generally continued for at least 28 days postoperatively; aspirin is among the accepted agents, although the consensus does not establish a preferred agent, dose, or duration. Aspirin may also be considered for patients undergoing knee osteotomy, while routine prophylaxis is not recommended for low-risk patients undergoing upper-extremity hardware removal. [2]
For Foot and Ankle, the ICM does not recommend routine chemoprophylaxis for low-risk patients undergoing elective forefoot/midfoot surgery with immediate weight-bearing, Achilles tendon repair, or ankle/hindfoot fusion. For total ankle arthroplasty, chemoprophylaxis may be appropriate in higher-risk patients, such as those with a prior VTE or known thrombophilia; however, the optimal approach remains uncertain. [3]
The 2019 American Society of Hematology (ASH) guidelines suggest either aspirin or anticoagulants for VTE prophylaxis following THA or TKA (very low certainty of evidence). When anticoagulants are selected, direct oral anticoagulants (DOACs) are preferred over LMWH (moderate certainty of evidence). For hip fracture repair, pharmacological prophylaxis with LMWH or unfractionated heparin (UFH) is suggested (very low certainty of evidence). ASH classifies these as conditional recommendations and emphasizes that VTE prophylaxis following major surgery should be individualized based on patient-specific VTE and bleeding risks. Combined mechanical and pharmacological prophylaxis is particularly favored in patients at high risk of VTE. [4]
Similarly, a 2024 guideline by the European Society of Anaesthesiology and Intensive Care (ESAIC), along with 11 partnering international organizations, recommends VTE prophylaxis with aspirin, DOACs, or LMWH over no prophylaxis after fast-track THA or TKA. However, no specific dosing guidance is provided. [5]
The Western Trauma Association (WTA) does not recommend aspirin or DOACs as first-line pharmacological prophylaxis for most trauma patients due to limited clinical trial evidence. However, aspirin may be considered for patients with isolated orthopedic injuries who decline injectable prophylaxis and for postdischarge prophylaxis in high-VTE-risk trauma patients, including those with orthopedic injuries or following major orthopedic surgery. Although thromboelastography (TEG) has not been validated for monitoring pharmacological prophylaxis, TEG with platelet mapping may help identify platelet-related hypercoagulability and guide the addition of aspirin to the prophylactic regimen. In this setting, an initial dose of 81 mg daily is recommended, with potential escalation to 325 mg daily based on subsequent TEG results. [6]
While the American Academy of Orthopaedic Surgeons (AAOS) strongly recommends VTE prophylaxis for hip fractures in older adults, it notes there is limited evidence available to recommend a specific pharmacological agent or duration of treatment. AAOS advises that patient specific factors, such as patient immobility, comorbidities, or bleeding risks, should be taken into consideration when selecting an anticoagulant agent and notes that aspirin may be a cost-effective agent for appropriately selected patients. [7]
A 2024 literature review assessed the efficacy of aspirin compared to other thromboprophylactic agents in patients undergoing THA. The review included six primary studies published between 2020 and 2024, comprising both retrospective cohort studies and one prospective randomized controlled trial (RCT), known as the CRISTAL study (Table 4). The analysis involved data from thousands of patients, with particular focus on the incidence of symptomatic VTE within 90 days post-surgery. The review highlighted variations in outcomes across the included studies. For instance, the CRISTAL RCT reported a higher VTE rate in aspirin users compared to those on LMWH, while several retrospective analyses suggested that aspirin could be non-inferior to other anticoagulants, particularly in low-risk patients. The Moore et al. 2023 study showed a significantly lower VTE rate in aspirin users compared to other agents, potentially due to aspirin's prevalent use in patients at lower VTE risk. The review concludes that while aspirin shows promise as a thromboprophylactic agent in specific patient subsets, further randomized trials are necessary to affirm its comparative effectiveness broadly across all THA patients. [8]
A 2021 systematic review and meta-analysis of 14 studies involving 161,463 patients undergoing total hip THA or TKA found that aspirin was associated with a significantly higher risk of VTE (odds ratio [OR] 1.56, 95% CI 1.21 to 2.01), pulmonary embolism ([PE]; OR 1.63, 95% CI 1.31 to 2.04), and overall mortality (OR 1.35, 95% CI 1.04 to 1.74) compared with DOACs, with no significant difference in bleeding risk. In contrast, a 2025 systematic review and meta-analysis of 11 randomized controlled trials involving 4,717 patients undergoing TJA found no significant difference in VTE incidence between aspirin and oral anticoagulants ([OACs]; relative risk [RR] 1.11, 95% CI 0.93 to 1.32), including deep vein thrombosis ([DVT]; RR 1.12, 95% CI 0.90 to 1.40) and PE (RR 1.18, 95% CI 0.51 to 2.71). No significant differences were observed in bleeding, wound complications, or mortality. Notably, the OAC comparators were limited to rivaroxaban and warfarin, and apixaban was not evaluated. Subgroup analyses by aspirin dose, type of joint surgery, OAC comparator, study region, and other variables were generally consistent with the overall findings, without identifying a specific subgroup in which aspirin demonstrated superior efficacy. A 2024 Bayesian network meta-analysis involving 31,705 patients undergoing THA identified aspirin, along with apixaban and dabigatran, as demonstrating notable effectiveness for PE prevention. Aspirin was also among the agents associated with lower rates of major hemorrhage, although apixaban demonstrated the most favorable overall balance of efficacy and safety. A separate 2024 network meta-analysis involving 29,678 patients undergoing TKA similarly favored apixaban overall. Additionally, a 2017 retrospective database analysis cited in the 2022 International Consensus Meeting on VTE guidelines compared aspirin, warfarin, enoxaparin, and factor Xa inhibitors following TKA. At 90 days, factor Xa inhibitors were associated with the lowest incidences of DVT (2.9%) and PE (0.9%), whereas aspirin was associated with the lowest incidence of postoperative anemia (19%) and the lowest transfusion requirement (7%), without a significant increase in bleeding-related complications. Overall, the available evidence suggests that aspirin may provide comparable VTE prophylaxis to certain OACs following TJA, although some analyses have identified higher rates of VTE, PE, and mortality compared with DOACs. Aspirin has also demonstrated favorable outcomes for selected safety endpoints, particularly postoperative anemia, transfusion requirements, and major hemorrhage. [9], [10], [11], [12]
Additional systematic reviews and meta-analyses have reported mixed findings regarding the comparative efficacy of aspirin for VTE prophylaxis following major orthopedic surgery. A 2023 meta-analysis of 17 RCTs involving 29,522 patients undergoing major orthopedic surgery found that aspirin was associated with a significantly higher incidence of VTE (RR 1.45, 95% CI 1.18 to 1.77) and proximal DVT and/or PE (RR 1.19, 95% CI 1.02 to 1.39) compared with other anticoagulants, including enoxaparin, rivaroxaban, dalteparin, warfarin, and LMWH. Subgroup analyses demonstrated a significantly higher VTE risk with aspirin following both trauma-related surgery (RR 1.39, 95% CI 1.14 to 1.74) and total hip or knee arthroplasty (RR 1.39, 95% CI 1.02 to 1.90). However, when aspirin was combined with mechanical prophylaxis, the difference in VTE incidence was not statistically significant (RR 1.38, 95% CI 0.99 to 1.91), whereas aspirin without mechanical prophylaxis was associated with a significantly higher VTE risk (RR 1.47, 95% CI 1.12 to 1.92). Additionally, three trials evaluating aspirin 325 mg twice daily found no significant difference in VTE incidence compared with enoxaparin or warfarin, although these findings were based on limited data. No significant differences were observed in bleeding events, wound complications, wound infections, transfusion requirements, or mortality. In contrast, a 2020 systematic review and meta-analysis of 13 RCTs involving 6,060 patients undergoing total hip replacement (THR) or total knee replacement (TKR) found no significant difference in VTE incidence between aspirin and other anticoagulants (RR 1.12, 95% CI 0.78 to 1.62), including DVT (RR 1.04, 95% CI 0.72 to 1.51) and PE (RR 1.01, 95% CI 0.68 to 1.48). Subgroup analyses demonstrated similar findings in THR and TKR populations, with no significant differences in VTE risk when aspirin was compared specifically with LMWH (RR 0.76, 95% CI 0.37 to 1.56) or rivaroxaban (RR 1.52, 95% CI 0.56 to 4.12). Rates of major bleeding, wound hematoma, and wound infection were also comparable between treatment groups. However, substantial heterogeneity was observed across studies (I²=63%), and aspirin dosing and treatment durations varied considerably in both meta-analyses. Overall, these findings suggest that aspirin may provide comparable VTE prophylaxis to other anticoagulants in certain orthopedic surgical settings, although the larger 2023 meta-analysis identified a significantly higher overall VTE risk. Neither analysis identified specific subgroups in which aspirin demonstrated statistically superior VTE prevention. [13], [14]
A 2022 multicenter retrospective cohort study evaluated the efficacy of aspirin as VTE prophylaxis in ambulatory patients with femoral neck fractures undergoing either total hip arthroplasty or hemiarthroplasty ( Table 2). The analysis included 1,141 patients, with 454 receiving aspirin and 687 receiving other anticoagulants, including warfarin, LMWH, heparin, clopidogrel, and factor Xa inhibitors. The primary outcome was the occurrence of symptomatic VTE, specifically DVT or PE, confirmed by imaging, within 90 days following the surgical procedure. Anticoagulation was administered according to the protocol, with all patients receiving standard mechanical prophylaxis and early mobilization postoperatively. All patients received VTE prophylaxis for 4 to 6 weeks. For those receiving aspirin, the dosage was either 81 mg or 325 mg twice daily. However, due to insufficient power for comparison between the two aspirin doses, patients treated with aspirin were grouped for analysis. Aspirin demonstrated noninferiority compared to more potent anticoagulants, with an overall VTE incidence of 1.98% in patients receiving aspirin versus 6.7% in those receiving other agents (p<0.001). Patients who underwent hemiarthroplasty had symptomatic VTE rates of 2.19% for those who received aspirin and 6.33% for those who did not receive aspirin (p= 0.060). Additionally, there were no significant differences in symptomatic deep vein thrombosis, pulmonary embolism, or overall VTE events between both cohorts. Secondary outcomes such as wound complications, periprosthetic joint infections, and 90-day readmissions exhibited comparable rates. The findings suggest that aspirin may be an effective option for standard-risk ambulatory patients undergoing hip arthroplasty, or hemiarthroplasty for femoral neck fractures. [15]
A 2024 review examined VTE in orthopedic trauma surgery, summarizing incidence rates, risk factors, diagnostic approaches, and evolving prophylactic strategies based on prospective cohorts, registries, and RCTs. Symptomatic VTE incidence varied by injury type, with pelvic and acetabular fractures associated with notably higher rates (up to 37%) than more distal extremity injuries. Identified patient- and injury-specific risk factors included advanced age, delayed surgery, elevated BMI, and fracture pattern. Although LMWH has historically been the standard of care, the review discussed emerging evidence supporting aspirin and DOACs, including rivaroxaban and apixaban, as alternative prophylactic agents. A multicenter trial involving over 12,000 patients demonstrated aspirin’s noninferiority to LMWH for 90-day mortality and comparable PE rates following orthopedic trauma, although DVT rates were higher with aspirin. Additionally, available studies suggest DOACs may provide comparable VTE prevention and bleeding profiles to LMWH, with potentially better adherence, particularly in patients with hip and lower-extremity fractures. The review also addressed perioperative management of patients already receiving DOACs, noting that urgent surgery may not necessarily require delay solely for anticoagulant clearance. Mechanical prophylaxis remains an important adjunct, particularly when pharmacological prophylaxis is contraindicated. Overall, the review emphasizes individualized prophylaxis based on patient and injury characteristics, with further research needed to optimize agent selection, duration, and laboratory-guided approaches. [16]