Aims. The aim of this study was to evaluate the healthcare costs and benefits of enoxaparin compared to aspirin in the prevention of symptomatic venous thromboembolism (VTE) after total hip arthroplasty (THA) or total knee arthroplasty (TKA) using data from the CRISTAL trial. Methods. This trial-based economic analysis reports value for money as incremental cost per quality-adjusted life-year (QALY) gained in 2022 Australian dollars, compared to a single threshold value of AUD$70,000 per QALY. Event costs were estimated based on occurrence of VTEs and bleeds, and on published guidelines for treatment. Unit costs were taken from Australian sources. QALYs were estimated using CRISTAL six-month follow-up data. Sensitivity analyses are presented that vary the cost of VTE treatment, and extend the analyses to two years. Results. The CRISTAL trial found that enoxaparin was more effective than aspirin in preventing symptomatic VTE within 90 days of THA or TKA (risk difference 1.97% (95% confidence interval (CI) 0.54% to 3.41%; p = 0.007)). The additional cost after a THA or TKA was AUD$83 (95% CI 68 to 97) for enoxaparin, and enoxaparin resulted in an additional 0.002 QALYs (95% CI -0.002 to 0.005). Incremental cost per QALY gained was AUD$50,567 (95% CI 15,513, dominated) for enoxaparin. We can be 60% confident that the incremental cost per QALY does not exceed the willingness-to-pay threshold of AUD$70,000. Increasing the cost of VTE treatment and extension of costs and consequences to two years suggested greater confidence that enoxaparin is good value for money (70% and 63% confidence, respectively). Conclusion. This analysis provides strong evidence that enoxaparin thromboprophylaxis following THA or TKA reduced VTEs, but weak evidence of net economic benefits over aspirin. If the value of avoiding VTEs is high, and there is a strong likelihood of VTE-related health impairments, we can be more confident that enoxaparin is cost-effective compared to aspirin. Cite this article: Bone Joint J 2024;106-B(6):589–595

Aims. The optimal management of an infrapopliteal deep venous thrombosis (IDVT) following total knee arthroplasty (TKA) remains unknown. The risk of DVT propagation and symptom progression must be balanced against potential haemorrhagic complications associated with administration of anticoagulation therapy. The current study reports on a cohort of patients diagnosed with IDVT following TKA who were treated with aspirin, followed closely for development of symptoms, and scanned with ultrasound to determine resolution of IDVT. Methods. Among a cohort of 5,078 patients undergoing TKA, 532 patients (695 TKAs, 12.6%) developed an IDVT between 1 January 2014 to 31 December 2019 at a single institution, as diagnosed using Doppler ultrasound at the first postoperative visit. Of the entire cohort of 532 patients with IDVT, 91.4% (486/532) were treated with aspirin (325 mg twice daily) and followed closely. Repeat lower limb ultrasound was performed four weeks later to evaluate the status of IDVT. Results. Follow-up Doppler ultrasound was performed on 459/486 (94.4%) patients and demonstrated resolution of IDVT in 445/459 cases (96.9%). Doppler diagnosed propagation of IDVT to the popliteal vein had occurred in 10/459 (2.2%) cases. One patient with an IDVT developed a pulmonary embolus six weeks postoperatively. Conclusion. The results of this study demonstrate a low rate of IDVT propagation in patients managed with aspirin. Additionally, no significant bleeding episodes, wound-related complications, or other adverse events were noted from aspirin therapy. Cite this article: Bone Joint J 2021;103-B(6 Supple A):18–22

Aims. There is uncertainty regarding the optimal means of thromboprophylaxis following total hip and knee arthroplasty (THA, TKA). This systematic review presents the evidence for acetylsalicylic acid (aspirin) as a thromboprophylactic agent in THA and TKA and compares it with other chemoprophylactic agents. Materials and Methods. A search of literature published between 2004 and 2014 was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 13 studies were eligible for inclusion. Results. Evidence from one good quality randomised controlled trial (RCT) showed no difference in rates of venous thrombo-embolism (VTE) in patients given aspirin or low molecular weight heparin (LMWH) following TKA. There was insufficient evidence from trials with moderate to severe risk of bias being present to suggest aspirin is more or less effective than LMWH, warfarin or dabigatran for the prevention of VTE in TKA or THA. Compared with aspirin, rates of asymptomatic deep vein thrombosis (DVT) in TKA may be reduced with rivaroxaban but insufficient evidence exists to demonstrate an effect on incidence of symptomatic DVT. Compared with aspirin there is evidence of more wound complications following THA and TKA with dabigatran and in TKA with rivaroxaban. Some studies highlighted concerns over bleeding complications and efficacy of aspirin. Conclusion. The results suggest aspirin may be considered a suitable alternative to other thromboprophylactic agents following THA and TKA. Further investigation is required to fully evaluate the safety and efficacy of aspirin. Cite this article: Bone Joint J 2016;98-B:1056–61

The number of arthroplasties being performed increases each year. Patients undergoing an arthroplasty are at risk of venous thromboembolism (VTE) and appropriate prophylaxis has been recommended. However, the optimal protocol and the best agent to minimise VTE under these circumstances are not known. Although many agents may be used, there is a difference in their efficacy and the risk of bleeding. Thus, the selection of a particular agent relies on the balance between the desire to minimise VTE and the attempt to reduce the risk of bleeding, with its undesirable, and occasionally fatal, consequences. Acetylsalicylic acid (aspirin) is an agent for VTE prophylaxis following arthroplasty. Many studies have shown its efficacy in minimising VTE under these circumstances. It is inexpensive and well-tolerated, and its use does not require routine blood tests. It is also a ‘milder’ agent and unlikely to result in haematoma formation, which may increase both the risk of infection and the need for further surgery. Aspirin is also unlikely to result in persistent wound drainage, which has been shown to be associated with the use of agents such as low-molecular-weight heparin (LMWH) and other more aggressive agents. The main objective of this review was to summarise the current evidence relating to the efficacy of aspirin as a VTE prophylaxis following arthroplasty, and to address some of the common questions about its use. . There is convincing evidence that, taking all factors into account, aspirin is an effective, inexpensive, and safe form of VTE following arthroplasty in patients without a major risk factor for VTE, such as previous VTE. Cite this article: Bone Joint J 2017;99-B:1420–30

We compared thromboembolic events, major haemorrhage and death after total hip replacement in patients receiving either aspirin or low-molecular-weight heparin (LMWH). We analysed data from the National Joint Registry for England and Wales linked to an administrative database of hospital admissions in the English National Health Service. A total of 108 584 patients operated on between April 2003 and September 2008 were included and followed up for 90 days. Multivariable risk modelling and propensity score matching were used to estimate odds ratios (OR) adjusted for baseline risk factors. An OR <  1 indicates that rates are lower with LMWH than with aspirin. In all, 21.1% of patients were prescribed aspirin and 78.9% LMWH. Without adjustment, we found no statistically significant differences. The rate of pulmonary embolism was 0.68% in both groups and 90-day mortality was 0.65% with aspirin and 0.61% with LMWH (OR 0.93; 95% CI 0.77 to 1.11). With risk adjustment, the difference in mortality increased (OR 0.84; 95% CI 0.69 to 1.01). With propensity score matching the mortality difference increased even further to 0.65% with aspirin and 0.51% with LMWH (OR 0.77; 95% CI 0.61 to 0.98). These results should be considered when the conflicting recommendations of existing guidelines for thromboprophylaxis after hip replacement are being addressed

We compared thromboembolic events, major haemorrhage and death after knee replacement in patients receiving either aspirin or low-molecular-weight heparin (LMWH). Data from the National Joint Registry for England and Wales were linked to an administrative database of hospital admissions in the English National Health Service. A total of 156 798 patients between April 2003 and September 2008 were included and followed for 90 days. Multivariable risk modelling was used to estimate odds ratios adjusted for baseline risk factors (AOR). An AOR < 1 indicates that risk rates are lower with LMWH than with aspirin. In all, 36 159 patients (23.1%) were prescribed aspirin and 120 639 patients (76.9%) were prescribed LMWH. We found no statistically significant differences between the aspirin and LMWH groups in the rate of pulmonary embolism (0.49% vs 0.45%, AOR 0.88 (95% confidence interval (CI) 0.74 to 1.05); p = 0.16), 90-day mortality (0.39% vs 0.45%, AOR 1.13 (95% CI 0.94 to 1.37); p = 0.19) or major haemorrhage (0.37% vs 0.39%, AOR 1.01 (95% CI 0.83 to 1.22); p = 0.94). There was a significantly greater likelihood of needing to return to theatre in the aspirin group (0.26% vs 0.19%, AOR 0.73 (95% CI 0.58 to 0.94); p = 0.01). Between patients receiving LMWH or aspirin there was only a small difference in the risk of pulmonary embolism, 90-day mortality and major haemorrhage. These results should be considered when the existing guidelines for thromboprophylaxis after knee replacement are reviewed

Aims. The aim of this study was to present data on 11 459 patients who underwent total hip (THA), total knee (TKA) or unicompartmental knee arthroplasty (UKA) between November 2002 and April 2014 with aspirin as the primary agent for pharmacological thromboprophylaxis. . Patients and Methods. We analysed the incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE) then compared the 90-day all-cause mortality with the corresponding data in the National Joint Registry for England and Wales (NJR). . Results. The incidence of PE was 0.6% after THA, 1.47% after TKA and 1.2% after UKA. The 90-day mortality was 0.39% after THA and 0.44% after TKA. No deaths occurred after UKA. The main causes of death were ischaemic heart disease and respiratory failure. PE was responsible for only 18% of deaths. There was a decline in 90-day mortality, from 0.64% between 2002 and 2007, to 0.21% between 2008 and 2013 after THA, and from 0.47% to 0.39% after TKA for the corresponding period. The standardised mortality ratio (SMR) declined from 86.5 (confidence interval (CI) 63.0 to 137.7) to 39.7 (CI 31.2 to 54.3) p = 0.024. The incidence of proximal DVT was 0.3%. . Take home message: With individualised risk assessment and as part of a multimodal approach, Aspirin is safe to use as the main thromboprophylactic agent in primary arthroplasty. It is not associated with an increased incidence of symptomatic DVT, PE or death. . Cite this article: Bone Joint J 2016;98-B:341-8

The incidence of deep-vein thrombosis (DVT) and pulmonary embolism (PE) is thought to be low following foot and ankle surgery, but the routine use of chemoprophylaxis remains controversial. This retrospective study assessed the incidence of symptomatic venous thromboembolic (VTE) complications following a consecutive series of 2654 patients undergoing elective foot and ankle surgery. A total of 1078 patients received 75 mg aspirin as routine thromboprophylaxis between 2003 and 2006 and 1576 patients received no form of chemical thromboprophylaxis between 2007 and 2010. The overall incidence of VTE was 0.42% (DVT, 0.27%; PE, 0.15%) with 27 patients lost to follow-up. If these were included to create a worst case scenario, the overall VTE rate was 1.43%. There was no apparent protective effect against VTE by using aspirin. We conclude that the incidence of VTE following foot and ankle surgery is very low and routine use of chemoprophylaxis does not appear necessary for patients who are not in the high risk group for VTE

In a randomised trial we compared the effects of two different antithrombotic regimens on the incidence of venographically established deep venous thrombosis (DVT) in 83 patients undergoing surgery for fracture of the femoral neck. Group A received dextran 40 peroperatively plus 0.5 g aspirin a day beginning before operation and continuing for 10 days after. Group B received heparin calcium 5000 iu subcutaneously plus dihydroergotamine (DHE) 0.5 mg intramuscularly, given 8-hourly, beginning before operation and continuing for 10 days after. Two patients in Group A and three in Group B developed proximal DVT, while the incidence of all DVT was 33% in Group A and 29% in Group B, a difference which was not significant. Haemorrhagic complications were much more common in the dextran/aspirin group: the volume of drainage fluid, the number of patients transfused and quantity of blood transfused, and the drop in haemoglobin level were all significantly greater in Group A. We conclude that the DHE/heparin regime is preferable to dextran/aspirin because it is safer and no less effective

Aims. We investigated the efficacy and safety profile of commonly used venous thromboembolism (VTE) prophylaxis agents following hip and knee arthroplasty. Methods. A systematic search of PubMed, Embase, Cochrane Library, Web of Science, and OrthoSearch was performed. Prophylaxis agents investigated were aspirin (< 325 mg and ≥ 325 mg daily), enoxaparin, dalteparin, fondaparinux, unfractionated heparin, warfarin, rivaroxaban, apixaban, and dabigatran. The primary efficacy outcome of interest was the risk of VTE, whereas the primary safety outcomes of interest were the risk of major bleeding events (MBE) and wound complications (WC). VTE was defined as the confirmed diagnosis of any deep vein thrombosis and/or pulmonary embolism. Network meta-analysis combining direct and indirect evidence was performed. Cluster rank analysis using the surface under cumulative ranking (SUCRA) was applied to compare each intervention group, weighing safety and efficacy outcomes. Results. Of 86 studies eligible studies, cluster rank analysis showed that aspirin < 325 mg daily (SUCRA-VTE 89.3%; SUCRA-MBE 75.3%; SUCRA-WC 71.1%), enoxaparin (SUCRA-VTE 55.7%; SUCRA-MBE 49.8%; SUCRA-WC 45.2%), and dabigatran (SUCRA-VTE 44.9%; SUCRA-MBE 52.0%; SUCRA-WC 41.9%) have an overall satisfactory efficacy and safety profile. Conclusion. We recommend the use of either aspirin < 325 mg daily, enoxaparin, or dabigatran for VTE prophylaxis following hip and knee arthroplasty. Cite this article: Bone Joint J 2024;106-B(9):924–934

Aims. The aims of this study were to compare the efficacy of two agents, aspirin and warfarin, for the prevention of venous thromboembolism (VTE) after simultaneous bilateral total knee arthroplasty (SBTKA), and to elucidate the risk of VTE conferred by this procedure compared with unilateral TKA (UTKA). Patients and Methods. A retrospective, multi-institutional study was conducted on 18 951 patients, 3685 who underwent SBTKA and 15 266 who underwent UTKA, using aspirin or warfarin as VTE prophylaxis. Each patient was assigned an individualised baseline VTE risk score based on a system using the Nationwide Inpatient Sample. Symptomatic VTE, including pulmonary embolism (PE) and deep vein thrombosis (DVT), were identified in the first 90 days post-operatively. Statistical analyses were performed with logistic regression accounting for baseline VTE risk. Results. The adjusted incidence of PE following SBTKA was 1.0% (95% confidence interval (CI) 0.86 to 1.2) with aspirin and 2.2% (95% CI 2.0 to 2.4) with warfarin. Similarly, the adjusted incidence of VTE following SBTKA was 1.6% (95% CI 1.1 to 2.3) with aspirin and 2.5% (95% CI 1.9 to 3.3) with warfarin. The risk of PE and VTE were reduced by 66% (odds ratio (OR) 0.44, 95% CI 0.25 to 0.78) and 38% (OR 0.62, 95% CI 0.38 to 1.0), respectively, using aspirin. In addition, the risk of PE was 204% higher for patients undergoing SBTKA relative to those undergoing UTKA. For each ten-point increase in baseline VTE risk, the risk of PE increased by 25.5% for patients undergoing SBTKA compared with 10.5% for those undergoing UTKA. Patients with a history of myocardial infarction or peripheral vascular disease had the greatest increase in risk from undergoing SBTKA instead of UTKA. Conclusion. Aspirin is more effective than warfarin for the prevention of VTE following SBTKA, and serves as the more appropriate agent for VTE prophylaxis for patients in all risk categories. Furthermore, patients undergoing SBTKA are at a substantially increased risk of VTE, even more so for those with significant underlying risk factors. Patients should be informed about the risks associated with undergoing SBTKA. Cite this article: Bone Joint J 2018;100-B(1 Supple A):68–75

Aims. We studied the safety and efficacy of multimodal thromboprophylaxis in patients with a history of venous thromboembolism (VTE) who undergo total hip arthroplasty (THA) within the first 120 postoperative days, and the mortality during the first year. Multimodal prophylaxis includes discontinuation of procoagulant medications, VTE risk stratification, regional anaesthesia, an intravenous bolus of unfractionated heparin prior to femoral preparation, rapid mobilization, the use of pneumatic compression devices, and chemoprophylaxis tailored to the patient’s risk of VTE. Methods. Between 2004 to 2018, 257 patients with a proven history of VTE underwent 277 primary elective THA procedures by two surgeons at a single institution. The patients had a history of deep vein thrombosis (DVT) (186, 67%), pulmonary embolism (PE) (43, 15.5%), or both (48, 17.5%). Chemoprophylaxis included aspirin (38 patients), anticoagulation (215 patients), or a combination of aspirin and anticoagulation (24 patients). A total of 50 patients (18%) had a vena cava filter in situ at the time of surgery. Patients were followed for 120 days to record complications, and for one year to record mortality. Results. Postoperative VTE was diagnosed in seven patients (2.5%): DVT in five, and PE with and without DVT in one patient each. After hospitalization, three patients required readmiss-ion for evacuation of a haematoma, one for wound drainage, and one for monitoring of an elevated international normalized ratio (INR). Seven patients died (2.5%). One patient died five months postoperatively of a PE during open thrombectomy. She had discontinued anticoagulation. One patient died of a haemorrhagic stroke while receiving Coumadin. PE or bleeding was not suspected in the remaining five fatalities. Conclusion. Multimodal prophylaxis is safe and effective in patients with a history of VTE. Postoperative anticoagulation should be prudent as very few patients developed VTE (2.5%) or died of suspected or confirmed PE. Mortality during the first year was mostly unrelated to either VTE or bleeding. Cite this article: Bone Joint J 2020;102-B(7 Supple B):71–77

Aims. The place of thromboprophylaxis in arthroplasty surgery remains controversial, with a challenging requirement to balance prevention of potentially fatal venous thrombo-embolism with minimising wound-related complications leading to deep infection. We compared the incidence of fatal pulmonary embolism in patients undergoing elective primary total hip arthroplasty (THA) between those receiving aspirin, warfarin and low molecular weight heparin (LMWH) for the chemical component of a multi-modal thromboprophylaxis regime. Patients and Methods. A prospective audit database was used to identify patients who had died within 42 and 90 days of surgery respectively between April 2000 and December 2012. A case note review was performed to ascertain the causes of death. Results. During this period 7983 THAs were performed. The rate of mortality was 0.43% and 0.58% at 42 and 90 days respectively. The groups comprised 1571 patients (19.7%) on warfarin, 1838 (23.0%) on LMWH and 4574 (57.3%) on aspirin. The 90-day mortality for these three groups was 0.38%, 1.09% and 0.43% respectively. The higher mortality rate for LMWH was significant (p < 0.05). There were six fatal pulmonary emboli (PEs) (0.08%). A total of three occurred within 42 days, all in the LMWH group. A total of three occurred between 42 and 90 days; one on warfarin, two on LMWH. The leading causes of death in all three groups were lower respiratory tract infections and myocardial infarction. Conclusion. We confirmed that fatal PE following elective THA with a multi-modal prophylaxis regime is rare. We further found that LMWH conferred no benefit over aspirin in this context, and is associated with a higher all-cause rate of mortality. Take home message: This study proposes that aspirin may be an appropriate thromboprophylaxis agent when used as part of a multi-modal regimen, suggesting current guidelines should be reviewed. Cite this article: Bone Joint J 2016;98-B:585–8

Thromboprophylaxis after elective orthopaedic surgery remains controversial. Recent guidelines from the National Institute for Clinical Excellence (NICE) have suggested that low molecular weight heparin should be given to all patients undergoing total hip replacement. The British Orthopaedic Association is currently debating this guideline with NICE, as it is not clear whether published evidence supports this view. We present the early mortality in our unit after total hip replacement using aspirin as chemical thromboprophylaxis. The 30-day and 90-day mortality after primary total hip arthroplasty was zero. We compare this with that reported previously from our unit without using chemical thromboprophylaxis. With the introduction of routine aspirin thromboprophylaxis, deaths from cardiovascular causes have dropped from 0.75% to zero. These results demonstrate that there is a strong argument for the routine administration of aspirin after elective total hip replacement

We studied 4253 patients undergoing primary joint replacement between November 2002 and November 2007, of whom 4060 received aspirin only as chemical prophylaxis; 46 were mistakenly given low molecular weight heparin initially, which was stopped and changed to aspirin; 136 received no chemoprophylaxis and 11 patients received warfarin because of a previous history of pulmonary embolism. We identified the rate of clinical thromboembolism before and after discharge, and the mortality from pulmonary embolism at 90 days. The overall death rate was 0.31% (13 of 4253) and the rate of fatal pulmonary embolism was 0.07% (3 of 4253). Our data suggest that fatal pulmonary embolism is not common following elective primary joint replacement, and with modern surgical practice elective hip and knee replacement should no longer be considered high-risk procedures

We performed a meta-analysis of the English literature to assess the efficacy of four common regimes for thromboembolic prophylaxis after total knee arthroplasty: aspirin, warfarin, low-molecular-weight heparin (LMWH) and pneumatic compression. We reviewed 136 articles and abstracts published between January 1980 and December 1997. Papers not using routine venography and a lung scan or angiography to detect deep-venous thrombosis (DVT) and pulmonary emboli (PE) respectively, were excluded. Of the 136 studies, 23 with 6001 patients were selected. The incidence of DVT was 53% (1701/3214) in the aspirin group, 45% (541/1203) in the warfarin group, 29% (311/1075) in the LMWH group, and 17% (86/509) in the pneumatic compression device group. Intermittent pneumatic compression devices and LMWH were significantly better than warfarin (p < 0.0001) or aspirin (p < 0.0001) in preventing DVT. The incidence of asymptomatic PE was 11.7% in the aspirin group (222/1901), 8.2% (101/1229) in the warfarin group and 6.3% (24/378) in the pneumatic compression group. No studies with LMWH used routine lung scans. Warfarin and pneumatic compression were significantly better than aspirin in preventing asymptomatic PE (p < 0.05). The incidence of symptomatic PE was 1.3% (23/1800) in the aspirin group, 0.4% (2/559) in the warfarin group, 0.5% (2/416) in the LMWH group and 0% (0/177) in the pneumatic compression group. No statistically significant difference was noted between the above prophylatic regimes due to the very small incidence of symptomatic PE. Prophylaxis for thromboembolic disease in TKA may have to include a combination of some of the above regimes to incorporate their advantages

Aims. We studied the impact of direct anterior (DA) versus non-anterior (NA) surgical approaches on prosthetic joint infection (PJI), and examined the impact of new perioperative protocols on PJI rates following all surgical approaches at a single institution. Patients and Methods. A total of 6086 consecutive patients undergoing primary total hip arthroplasty (THA) at a single institution between 2013 and 2016 were retrospectively evaluated. Data obtained from electronic patient medical records included age, sex, body mass index (BMI), medical comorbidities, surgical approach, and presence of deep PJI. There were 3053 male patients (50.1%) and 3033 female patients (49.9%). The mean age and BMI of the entire cohort was 62.7 years (18 to 102, . sd. 12.3) and 28.8 kg/m. 2. (13.3 to 57.6, . sd. 6.1), respectively. Infection rates were calculated yearly for the DA and NA approach groups. Covariates were assessed and used in multivariate analysis to calculate adjusted odds ratios (ORs) for risk of development of PJI with DA compared with NA approaches. In order to determine the effect of adopting a set of infection prevention protocols on PJI, we calculated ORs for PJI comparing patients undergoing THA for two distinct time periods: 2013 to 2014 and 2015 to 2016. These periods corresponded to before and after we implemented a set of perioperative infection protocols. Results. There were 1985 patients in the DA group and 4101 patients in the NA group. The overall rate of PJI at our institution during the study period was 0.82% (50/6086) and decreased from 0.96% (12/1245) in 2013 to 0.53% (10/1870) in 2016. There were 24 deep PJIs in the DA group (1.22%) and 26 deep PJIs in the NA group (0.63%; p = 0.023). After multivariate analysis, the DA approach was 2.2 times more likely to result in PJI than the NA approach (OR 2.2 (95% confidence interval 1.1 to 3.9); p = 0.006) for the overall study period. Conclusion. We found a higher rate of PJI in DA versus NA approaches. Infection prevention protocols such as use of aspirin, dilute povidone-iodine lavage, vancomycin powder, and Gram-negative coverage may have been positively associated with diminished PJI rates observed for all approaches over time. Cite this article: Bone Joint J 2019;101-B(6 Supple B):2–8