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Aspirin as a thromboprophylaxis agent after revision knee arthroplasty: A retrospective analysis
∗Corresponding author: Ananth Srinivasan. ananth.srinivasan@nhs.net
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Received: ,
Accepted: ,
This article was originally published by Reed Elsevier India Pvt. Ltd. and was migrated to Scientific Scholar after the change of Publisher.
Abstract
Abstract
Total knee arthroplasty is a common and effective procedure. Although complication rates are low, certain complications such as venous thromboembolism are potentially serious. The optimal prophylactic agent and dosage after revision knee arthroplasty remains unclear. The main objective of this work was to study the efficacy and safety of aspirin as a thromboprophylaxis agent following revision knee arthroplasties.
A retrospective review of patients undergoing revision knee arthroplasty between 2013 and 2020at a University Teaching Hospital was undertaken. The primary outcome was the development of a symptomatic thromboembolic event requiring treatment within 90 days post-surgery. The secondary outcomes were adverse events associated with aspirin therapy: surgical site infection rate; incidence of major bleeding; readmission rate and mortality within 90 days post-surgery.
490 patients were included. 374 (76.3%) received prophylactic aspirin (150 mg once daily for 28 days) and 75 (15.3%) patients received dalteparin for 28 days due to contraindication to aspirin use. Those already receiving other thromboprophylaxis agents for pre-existing comorbidities continued these after relevant medical consultation. The overall rates of venous thromboembolism and symptomatic DVT after aspirin prophylaxis were 0.6% (3/490) and 0.8% (3/374), respectively. VTE incidence did not significantly differ between those administered aspirin and other agents. No patient experienced major bleeding within 90 postoperative days. Only 2 of 490 (0.4%) patients had wound infection requiring readmission; neither received prophylactic aspirin.
Extended out-of-hospital thromboembolic prophylaxis with aspirin may be at least as effective as other agents in patients undergoing revision knee arthroplasty. Aspirin is safe, effective, and cheap compared with other agents.
Abstract
Highlights
•Largest study including revision knee arthroplasty and aspirin use with 98% follow-up.•Aspirin is cheaper and likely as effective as other thromboprophylaxis agents in revision knee arthroplasty.•Aspirin has similar safety profile as other thromboprophylaxis agents.
Keywords
Revision knee arthroplasty
Aspirin
Venous thromboembolism
Deep vein thrombosis
1 Introduction
Total knee arthroplasty is a common and effective procedure.1–4 Over 1 357 077 primary knee arthroplasty procedures have been registered in the United Kingdom National Joint Registry since 2003 with 260 620 procedures performed between 2018 and 2020.5 40 451 cases have undergone first-time revision with 10% of procedures performed in 2020 alone, indicating rising arthroplasty revision rates with the ageing population.5 Major post-operative complications following knee arthroplasty include venous thromboembolisms (VTE) that confer increased length of hospital stay; potentially worse functional outcomes; patient morbidity and mortality,6 in addition to increased financial burden on health services.6
The incidence of VTE following lower limb, large joint arthroplasty ranged from 20 to 40% prior to the utilisation of peri-operative thromboprophylaxis.6 Following the introduction of chemical thromboprophylaxis measures in 2001, the VTE rate has reduced significantly to ∼1–2%. A spectrum of thromboprophylaxis agents and approaches may be utilised following hip and knee arthroplasty, however the optimal strategy remains unclear.7 Although these thromboprophylaxis agents effectively prevent deep vein thromboses (DVT) and pulmonary embolisms (PE), great care is necessary to minimise bleeding complications. Excessive antithrombotic agent use may result in major bleeding including gastrointestinal or cerebrovascular haemorrhage in addition to increased risks of surgical wound drainage and periprosthetic infections.8,9 The efficacy and risks of major bleeding differ between the various thromboprophylaxis agents.10 In a resource starved National Health Service, the anti-thrombotic profile side effects along with the significant variability in cost per unit are taken into account when agreeing on a particular thromboprophylaxis agent.10
The optimal thromboprophylaxis agent, dosage and duration following revision joint arthroplasty remains unclear in literature. Numerous studies have shown the efficacy of prophylactic aspirin in minimising VTE incidence following primary joint arthroplasty. Aspirin seems to be an effective, well tolerated, inexpensive agent that does not necessitate monitoring blood tests. Furthermore, aspirin use is highly unlikely to lead to haematoma formation, which may increase the risk of surgical site infection and need for further operative intervention or revision procedures. The risk of persistent wound drainage is also lower with aspirin than with other more potent agents such as low-molecular-weight heparin (LMWH).11–14
There is a dearth of literature considering aspirin use in revision knee arthroplasty. Both primary and revision procedures are often grouped resulting in significant patient heterogeneity and subsequently smaller proportions of revision knee patients for analysis. The main objectives of this single-centre retrospective study was to Ref. 1 analyse the efficacy and2 safety of aspirin as a thromboprophylaxis agent in patients undergoing revision knee arthroplasty.
2 Material & methods
2.1 Study inclusion
A retrospective review was undertaken of revision knee arthroplasty cases at a single, large University Teaching Hospital from the 1st January 2013 to 31st December 2020. The University Teaching Hospital is the regional arthroplasty revision hub and hence also receives referrals from surrounding district general hospitals. Cases were identified from Trust datasets and corroborated with theatre surgical logbooks and radiographs. Clinical data archives, operation notes and clinic letters were reviewed and data pertaining to patient demographics, diagnoses, prostheses-used and complications were collected. Thromboprophylaxis agent, dose and duration were obtained from scanned inpatient drug charts and hospital discharge summaries. These data were analysed, and the outcome framework was applied to validate the efficacy of aspirin for thromboprophylaxis after revision knee arthroplasty.
2.2 Standard practice
2.2.1 Post-operative thromboprophylaxis
Standard practice at the University Teaching Hospital is a hybrid approach for thromboprophylaxis following revision knee arthroplasty. Inpatients receive once daily subcutaneous LMWH (Dalteparin or Enoxaparin) at a mass-adjusted dose (started 6 h following the operation and continued for the length of inpatient stay), followed by aspirin at a dose of 150 mg once daily for four weeks. In the case of an aspirin allergy, mass-adjusted once daily LMWH is prescribed for a total period of four weeks. In the event of relative or absolute contraindications including active gastrointestinal ulcers, recent gastrointestinal bleeding, severe liver disorders, or thrombocytopenia, specialist Haematology advice is sought for an alternative strategy. Patients’ own long-term anticoagulation, for prior medical conditions, were accepted as adequate thromboprophylaxis. Except in patients with contraindications, mechanical VTE prophylaxis in the form of thromboembolic deterrent stockings was prescribed for six weeks from the day of surgery.
2.2.2 Local venous thrombo-embolism service
Patients presenting with symptoms and signs suggestive of a DVT or PE are assessed with the Wells’ score and a duplex scan is undertaken to confirm the diagnosis, site and extent of the DVT. A computed tomography pulmonary angiogram is performed if a PE is suspected.
Patients with symptomatic thromboembolism may be managed in the community or under various parent hospital specialties including Emergency Medicine, Acute Internal Medicine, Respiratory medicine, Haematology and Orthopaedic Surgery (if the patient is clinically stable; presents within a week of post-operative discharge and is hence considered a failed discharge). Fortunately, all patients presenting to our Trust with a symptomatic thromboembolism, regardless of parent specialty, are prospectively included in a VTE database. A VTE specialist nurse is responsible for the assessment and follow-up of these patients. In addition to reviewing electronic data archives, the authors extracted pertinent data from this contemporaneous VTE database.
2.3 Outcomes
The primary outcome was the incidence of symptomatic thromboembolic events (DVT or PE), at any point up to 90 days post-surgery. The secondary outcomes were adverse events associated with chemical thromboprophylaxis therapy including the rate of surgical site infections, incidence of major bleeding, readmission rate and mortality within 90 days after surgery.
2.4 Statistics
Categorical data is presented as numbers with percentages. The Chi-squared test was used for categorical data; the Fisher's exact or Monte Carlo correction tests were used when more than 20% of the cells had an expected count of less than five. Continuous data were tested for normality using the Kolmogorov-Smirnov test and are presented as either means (with standard deviation) or medians. The Student t- and Mann Whitney U- tests were used to compare two categories of continuous and skewed data, respectively. A P value of <0.05 was deemed to be statistically significant. Data were analysed using SPSS version 26 (IBM, Armonk, NY).
3 Results
3.1 Patient inclusion
501 patients underwent revision knee arthroplasty between the 1st January 2013 and 31st December 2020. Eleven (11/501, 2%) patients were followed-up elsewhere. The average length of hospital stay for revision knee arthroplasty was 7.9 days. At the time of statistical analysis, 431 (431/490, 88%) patients were alive and 59 (59/490, 12%) had died. No patient had died within 90 days of surgery conferring 98% follow-up rate for the primary and secondary outcomes.
3.2 Baseline characteristics
The mean age of the patient population was 70.2 ± 9.8 (42–94) years; 47.6% and 52.4% were men and women, respectively. At the time of surgery, 1.4%, 40.4%, 51.6%, and 6.5% were of ASA status I, II, III and IV, respectively. The mean body mass index (BMI) was 32.38 ± 8.05; 18.8% and 62.2% were overweight and obese, respectively. Demographic data of the studied population is presented in Table 1.
| Demographic data | Number (%) |
| Gender | |
| Male | 233 (47.6%) |
| Female | 257 (52.4%) |
| Age | |
| 40–49 | 8 (1.6%) |
| 50–59 | 64 (13.1%) |
| 60–69 | 150 (30.6%) |
| 70–79 | 181 (36.9%) |
| 80–89 | 82 (16.7%) |
| 90+ | 5 (1.0%) |
| Mean ± SD | 70.21 ± 9.81 |
| Median (Min. – Max.) | 70.0 (42.0–94.0) |
| Side | |
| Right | 253 (51.6%) |
| Left | 237 (48.4%) |
| UK National Joint Registry Consent | |
| No | 145 (29.6%) |
| Yes | 345 (70.4%) |
| ASA | |
| I | 7 (1.4%) |
| II | 198 (40.4%) |
| III | 253 (51.6%) |
| IV | 32 (6.5%) |
| BMI | |
| Underweight | 14 (2.9%) |
| Normal | 79 (16.1%) |
| Overweight | 92 (18.8%) |
| Obese | 305 (62.2%) |
| Mean ± SD | 32.38 ± 8.05 |
| Median (Min. – Max.) | 32.0 (18.0–51.0) |
3.3 Indication for revision
The indications for revision knee arthroplasty included prosthetic joint infection (29.7%); aseptic loosening (23.4%); peri-prosthetic fracture (14.3%); instability (10.3%); polyethylene wear (8.7%); progression of arthritis in the context of a unicompartmental knee arthroplasty (7.9%); stiffness (2.3%), dislocation/subluxation (1.4%); secondary patellar resurfacing (1.5%) and pain (0.5%).
3.4 Thromboprophylaxis
374 (374/490, 76.3%) patients received prophylactic aspirin (150 mg once daily) for four weeks following discharge, 75 (75/490, 15.3%) patients were prescribed mass-adjusted LMWH owing to contraindications to aspirin use. The patients already receiving novel oral anticoagulants (24/490, 4.9%), warfarin (12/490, 2.4%) or other antiplatelet agents (5/490, 1.0%) for prior medical comorbidities recommenced said medications postoperatively following relevant medical consultation. The numbers of patients treated with different pharmacological VTE prophylaxis agents after revision knee arthroplasty is presented in Table 2.
| VTE | Number (%) | Dose |
| Aspirin | 374 (76.3%) | 150.0 mg |
| Dalteparin | 75 (15.3%) | 5000 IU |
| Clopidogrel | 5 (1%) | 75 mg |
| Apixaban | 17 (3.5%) | 5.0 mg |
| Rivaroxaban | 7 (1.4%) | 20.0 mg |
| Warfarin | 12 (2.4%) | Variable |
3.5 Primary outcome – incidence of venous thromboembolism
The overall rate of symptomatic thromboembolic events was 0.6% (3/490) and all cases occurred in patients receiving aspirin prophylaxis (3/374, 0.8%). All events were DVTs that occurred distal to the popliteal fossa at the level of the gastrocnemius muscle. One diagnosed case of superficial thrombophlebitis was excluded.
Statistical analysis demonstrated no significant difference in the incidence of DVT between those administered aspirin and other thromboprophylaxis agents (p = 1). No statistically significant relationship was found with any other factors including gender, age, laterality, ASA grade and Body Mass Index or revision indication (p > 0.05) (Table 3).
| Demographic data | PE/distal DVT | p | |
| No (n = 487) | Yes (n = 3) | ||
| Gender | |||
| Male | 230 (47.2%) | 3 (100.0%) | FEp = 0.107 |
| Female | 257 (52.8%) | 0 (0.0%) | |
| Age | |||
| 40–49 | 8 (1.6%) | 0 (0.0%) | MCp = 0.764 |
| 50–59 | 64 (13.1%) | 0 (0.0%) | |
| 60–69 | 148 (30.4%) | 2 (66.7%) | |
| 70–79 | 180 (37.0%) | 1 (33.3%) | |
| 80–89 | 82 (16.8%) | 0 (0.0%) | |
| 90+ | 5 (1.0%) | 0 (0.0%) | |
| Mean ± SD | 70.24 ± 9.83 | 65.33 ± 5.86 | 0.388 |
| Median (Min.- Max.) | 70.0 (42.0–94.0) | 63.0 (61.0–72.0) | |
| Laterality | |||
| Right | 252 (51.7%) | 1 (33.3%) | FEp = 0.612 |
| Left | 235 (48.3%) | 2 (66.7%) | |
| ASA | |||
| I | 7 (1.4%) | 0 (0.0%) | MCp = 0.285 |
| II | 197 (40.5%) | 1 (33.3%) | |
| III | 252 (51.7%) | 1 (33.3%) | |
| IV | 31 (6.4%) | 1 (33.3%) | |
| BMI | |||
| Underweight | 13 (2.7%) | 1 (33.3%) | MCp = 0.072 |
| Normal | 78 (16.0%) | 1 (33.3%) | |
| Overweight | 92 (18.9%) | 0 (0.0%) | |
| Obese | 304 (62.4%) | 1 (33.3%) | |
| Mean ± SD | 32.43 ± 8.03 | 24.33 ± 10.12 | 0.113 |
| Median (Min.- Max.) | 32.0 (18.0–51.0) | 19.0 (18.0–36.0) | |
3.6 Secondary outcomes
No patient had major postoperative bleeding requiring admission or blood transfusion. Two (2/490, 0.4%) developed surgical site infections requiring readmission; neither received postoperative thromboprophylaxis with aspirin.
4 Discussion
The literature on thromboprophylaxis after primary total joint arthroplasty has rapidly grown in recent years. However, there are few dedicated articles reviewing aspirin use in revision lower limb arthroplasty, which are longer and more complex procedures. This is one of the larger studies to date that reviews aspirin thromboprophylaxis particularly after revision knee arthroplasty surgery. Aspirin, a significantly cheaper agent, may be just as safe and effective as LMWH, NOACs and warfarin.
A systematic review and meta-analysis of 13 randomised controlled trials with 6060 participants demonstrated that the rate of VTE following primary joint arthroplasty surgery (total hip and knee arthroplasty) was 1.12% with aspirin; there was no statistically significant difference when compared with other thromboprophylaxis agents including LMWH and rivaroxaban. The risk of major bleeding, wound haematoma and infection were similar between patients receiving aspirin and the other agents.14 Complication rates including VTE are expected to be higher following revision joint arthroplasty given the prolonged operation times and extensive soft tissue dissection. However, literature demonstrates that revision surgery alone may not be a risk factor for DVT or PE.15Studies demonstrate that the rate of DVT after revision total knee arthroplasty has decreased in recent years, becoming comparable to those of primary total knee arthroplasty6,16–18. Shahi et al. reviewed the National Inpatient Sample of the United States between 2002 and 2011 and found that 0.88% and 0.34% cases of revision knee arthroplasty developed DVT and PE, respectively, while the DVT rate with primary knee arthroplasty was 1.03%. In 2019, Warren et al. reviewed patients from the National Surgical Quality Improvement Program database who underwent revision knee arthroplasty over a 8 year period from 2008 and found an overall VTE rate of 1.2% (DVT: 0.9% and PE: 0.4%) compared to a rate of 1.4% for primary knee arthroplasty.18
The latest recommendations of the National Institute for Health and Care Excellence (2018 and updated in 2019) recommends that thromboprophylaxis is to be offered to patients undergoing elective knee arthroplasty surgery if the VTE risk outweighs that of bleeding. The recommendations indicate the use of either aspirin (75 mg or 150 mg), LMWH or rivaroxaban for 14 days in combination with anti-embolism stockings until discharge.19 The cost of a single dose of dalteparin (5000 units prefilled syringe for injection) is £2.80 in the National Health Service, while a single dose of aspirin (150 mg) costs £0.08; making dalteparin 35 fold more expensive per day.20 Our study demonstrated that aspirin offers safe, efficient, and cost effective prophylaxis against VTE following revision knee arthroplasty. To our knowledge, only one retrospective study has compared aspirin with warfarin for thromboprophylaxis following revision hip and knee arthroplasty, which concluded that aspirin demonstrates the same efficacy as warfarin in low-risk patients and may even reduce the risk for bleeding events.21 Another retrospective study included patients undergoing both primary and revision surgery and compared outcomes between rivaroxaban, warfarin, and aspirin22.
In our study, the overall rates of DVT and PE within 90 days of surgery were 0.6% and 0%, respectively. In the aspirin group, the incidences of DVT and PE were 0.8% and 0%, respectively. The rate of major bleeding was 0% and the two cases of surgical site infection were not related to aspirin administration. The 90-day mortality rate was 0% and the overall mortality rate by the time of data review was 12%. These results are similar to or better than outcomes reported in literature.21,22 The first retrospective study of 2463 patients who underwent revision total joint arthroplasty between 2005 and 2013 compared aspirin to warfarin for VTE prophylaxis.21 The incidence of symptomatic VTE (1.75% vs. 0.56%) and major bleeding events (1.5% vs. 0.4%) were significantly higher with warfarin compared to aspirin. Variable dosing between patients and fluctuations in the depth of anticoagulation with warfarin may explain the latter findings. Another retrospective study reviewed 1917 patients undergoing primary or revision hip and knee joint arthroplasty. This study included 742 (38.7%) cases of primary total knee arthroplasty, 326 (17%) cases of revision total knee arthroplasty, 608 (31.7%) cases of primary total hip arthroplasty and 241 (12.6%) cases of revision total hip arthroplasty. Rivaroxaban was used in 40.6% of cases, followed by warfarin (28.5% cases) and aspirin (27.6% cases). The authors concluded that aspirin was as effective as other VTE prophylaxis agents and not associated with an increased risk of bleeding in low-risk patients.22 Our study has a greater number of revision knee arthroplasty patients receiving aspirin therapy with concordant results.
4.1 Limitations and strengths of the study
As a retrospective study with prospective data collection, there is a possibility of introducing selection bias. There was heterogeneity in operative indications, duration of inpatient LMWH use in the aspirin group and varying indications for the use of different thromboprophylaxis agents across the groups making firm conclusions difficult. Despite these limitations, this is one of the largest studies with high 90-day follow-up rate of 98%. By utilising the Trust's venous thromboembolism database, the authors have ensured robust identification of VTE events. The authors recommend future prospective study of aspirin use in lower limb revision arthroplasty given the financial advantage and similar safety profiles.
5 Conclusion
There is a paucity of literature on aspirin use in revision knee arthroplasty surgery. Our results demonstrate that extended out-of-hospital thromboprophylaxis with aspirin may be at least as effective as other prophylaxis agents in patients undergoing revision knee arthroplasty. Aspirin is as safe and significantly cheaper compared to other thromboprophylaxis agents. The study limitations have been discussed and future prospective research is warranted to form definitive conclusions.
Funding and sponsorship
This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.
Informed consent
Not applicable.
Institutional ethical committee approval
The project was registered locally with the Trust's Clinical Governance Team.
Author contributions
EA – Conceptualisation, Data curation, Formal Analysis, Methodology, Writing original draft, AS – Formal Analysis, Methodology, Visualisation, review and editing, AB – Conceptualisation, Methodology, Supervision, review and editing, SR – Data curation, AB – Conceptualisation, Supervision, management, review and editing, UC – Conceptualisation, Supervision, management, review and editing.
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