Aims

We investigated the efficacy and safety profile of commonly used venous thromboembolism (VTE) prophylaxis agents following hip and knee arthroplasty.

Thromboprophylaxis remains a controversial subject. A vast amount of epidemiological and trial data about venous thromboembolism has been published over the past 40 years. These data have been distilled and synthesised into guidelines designed to help the practitioner translate this extensive research into ‘evidence-based’ advice. Guidelines should, in theory, benefit patient care by ensuring that every patient routinely receives the best prophylaxis; without guidelines, it is argued, patients may fail to receive treatment or be exposed to protocols which are ineffective, dangerous or expensive. Guidelines, however, have not been welcomed or applied universally. In the United States, orthopaedic surgeons have published their concerns about the thromboprophylaxis guidelines prepared by the American College of Chest Physicians. In Britain, controversy persists with many surgeons unconvinced of the risk/benefit, cost/benefit or practicality of thromboprophylaxis. The extended remit of the recent National Institute of Clinical Excellence thromboprophylaxis guidelines has been challenged. The reasons for this disquiet are addressed in this paper and particular emphasis is placed on how clinically-acceptable guidelines could be developed and applied

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 risk of venous thromboembolism in patients following arthroplasty may be reduced by continuing chemical thromboprophylaxis for up to 35 days post-operatively. This prospective cohort study investigated the compliance of 40 consecutive consenting patients undergoing lower limb arthroplasty with self-administration of a recommended subcutaneous chemotherapeutic agent for six weeks after surgery. Compliance was assessed by examination of the patient for signs of injection, number of syringes used, and a self-report diary at the end of the six-week period. A total of 40 patients, 15 men and 25 women, were recruited. One woman was excluded because immediate post-operative complications prevented her participation. Self-administration was considered feasible in 87% of patients (95% confidence interval (CI) 76 to 98) at the time of discharge. Among this group of 34 patients, 29 (85%) were compliant (95% CI 73 to 97). Patients can learn to self-administer subcutaneous injections of thromboprophylaxis, and compliance with extended prophylaxis to six weeks is good

We report a retrospective review of the incidence of venous thromboembolism in 463 consecutive patients who underwent primary total hip arthroplasty (487 procedures). Treatment included both total hip replacement and hip resurfacing, and the patients were managed without anticoagulants. The thromboprophylaxis regimen included an antiplatelet agent, generally aspirin, hypotensive epidural anaesthesia, elastic compression stockings and early mobilisation. In 258 of these procedures (244 patients) performed in 2005 (cohort A) mechanical compression devices were not used, whereas in 229 (219 patients) performed during 2006 (cohort B) bilateral intermittent pneumatic calf compression was used. All operations were performed through a posterior mini-incision approach. Patients who required anticoagulation for pre-existing medical problems and those undergoing revision arthroplasty were excluded. Doppler ultrasonographic screening for deep-vein thrombosis was performed in all patients between the fourth and sixth post-operative days. All patients were reviewed at a follow-up clinic six to ten weeks after the operation. In addition, reponse to a questionnaire was obtained at the end of 12 weeks post-operatively. No symptomatic calf or above-knee deep-vein thrombosis or pulmonary embolism occurred. In 25 patients in cohort A (10.2%) and in ten patients in cohort B (4.6%) asymptomatic calf deep-vein thromboses were detected ultrasonographically. This difference was statistically significant (p = 0.03). The regimen followed by cohort B offers the prospect of a low incidence of venous thromboembolism without subjecting patients to the higher risk of bleeding associated with anticoagulant use

Tranexamic acid (TXA) has been used to reduce blood loss during total hip arthroplasty (THA), but its use could increase the risk of venous thromboembolic disease (VTE). Several studies have reported that TXA does not increase the prevalence of deep vein thrombosis (DVT), but most of those used routine chemical thromboprophylaxis, thereby masking the potential increased risk of TXA on VTE. We wished to ascertain whether TXA increases the prevalence of VTE in patients undergoing THA without routine chemical thromboprophylaxis. We carried out a retrospective case-control study in 254 patients who underwent a primary THA, 127 of whom received TXA (1 g given pre-operatively) and a control group of 127 who did not. All patients had mechanical but no chemical thomboprophylaxis. Each patient was examined for DVT by bilateral ultrasonography pre-operatively and on post-operative days 1 and 7. TXA was found to statistically significantly increase the incidence of total DVT on post-operative day 7 compared with the control group (24 (18.9%) and 12 (9.4%), respectively; p < 0.05) but most cases of DVT were isolated distal DVT, with the exception of one patient with proximal DVT in each group. One patient in the control group developed a non-fatal symptomatic pulmonary embolism (PE). The use of TXA did not appear to affect the prevalence of either proximal DVT or PE. Cite this article: Bone Joint J 2015; 97-B:458–62

The administration of heparin during operation has been reported to enhance the efficacy of thromboprophylaxis in patients undergoing total hip replacement. We have performed a small pilot study in which intraoperative doses of heparin were given in addition to the usual postoperative thromboprophylaxis with enoxaparin in 32 patients undergoing total knee replacement. The primary endpoint was deep-vein thrombosis (DVT) as demonstrated by bilateral venography on 6 ± 2 days after operation. Sixteen patients developed DVT; in two the thrombosis was proximal as well as distal and in one the occurrence was bilateral. There was one major haemorrhage. These results are similar to those obtained with the use of postoperative thromboprophylaxis with enoxaparin alone. They do not provide support for the initiation of a larger randomised trial of this approach to management

Aims. Cementless primary total hip arthroplasty (THA) is associated with risks of bleeding and thromboembolism. Anticoagulants are effective as venous thromboprophylaxis, but with an increased risk of bleeding. Tranexamic acid (TXA) is an efficient antifibrinolytic agent, but the mode and timing of its administration remain controversial. This study aimed to determine whether two intravenous (IV) TXA regimens (a three-hour two-dose (short-TXA) and 11-hour four-dose (long-TXA)) were more effective than placebo in reducing perioperative real blood loss (RBL, between baseline and day 3 postoperatively) in patients undergoing THA who receive rivaroxaban as thromboprophylaxis. The secondary aim was to assess the non-inferiority of the reduction of blood loss of the short protocol versus the long protocol. Patients and Methods. A multicentre, prospective, randomized, double-blind, placebo-controlled trial was undertaken involving 229 patients undergoing primary cementless THA using a posterior approach, whose extended rivaroxaban thromboprophylaxis started on the day of surgery. There were 98 male and 131 female patients, with a mean age of 65.5 years (32 to 91). The primary outcome, perioperative RBL, was evaluated at 72 hours postoperatively. The efficacy of short- and long-TXA protocols in the reduction of perioperative RBL was compared with a placebo group. Results. TXA significantly reduced perioperative blood loss compared with placebo (p < 0.001); the mean differences were 525.3 ml (short-TXA vs placebo) and 550.1 ml (long-TXA vs placebo). No venous or arterial thromboembolic complications were reported. The upper boundary of the 95% confidence interval, when comparing short and long protocols, was below the pre-specified margin of non-inferiority (p = 0.027). Conclusion. In patients undergoing primary cementless THA, using a posterior approach, who are treated with rivaroxaban for thromboembolic prophylaxis, short- and long-TXA IV protocols are significantly more effective than placebo in reducing perioperative RBL, without any thromboembolic complications. Non-inferiority of a short- versus a long-TXA protocol in reducing perioperative RBL was supported in a secondary analysis

We report the incidence and location of deep-vein thrombosis in 312 patients who had sustained high-energy, skeletal trauma. They were investigated using magnetic resonance venography and Duplex ultrasound. Despite thromboprophylaxis, 36 (11.5%) developed venous thromboembolic disease with an incidence of 10% in those with non-pelvic trauma and 12.2% in the group with pelvic trauma. Of patients who developed deep-vein thrombosis, 13 of 27 in the pelvic group (48%) and only one of nine in the non-pelvic group (11%) had a definite pelvic deep-vein thrombosis. When compared with magnetic resonance venography, ultrasound had a false-negative rate of 77% in diagnosing pelvic deep-vein thrombosis. Its value in the pelvis was limited, although it was more accurate than magnetic resonance venography in diagnosing clots in the lower limbs. Additional screening may be needed to detect pelvic deep-vein thrombosis in patients with pelvic or acetabular fractures

Prophylaxis against venous thromboembolism after elective total hip replacement is routinely recommended. Our preference has been to use mechanical prophylaxis without anticoagulant drugs. A randomised controlled trial was performed to evaluate whether the incidence of post-operative venous thromboembolism was reduced by using pharmacological anticoagulation with either fondaparinux or enoxaparin in addition to our prophylactic mechanical regimen. A total of 255 Japanese patients who underwent primary unilateral cementless total hip replacement were randomly assigned to one of three postoperative regimens, namely injection of placebo (saline), fondaparinux or enoxaparin. There were 85 patients in each group. All also received the same mechanical prophylaxis during and after the operation, regardless of their assigned group. The primary measurement of efficacy was the presence of a venous thromboembolic event by day 11, defined as deep-vein thrombosis detected by ultrasonography, documented symptomatic deep-vein thrombosis or documented symptomatic pulmonary embolism. The duration of follow-up was 12 weeks. The rate of venous thromboembolism was 7.2% with the placebo, 7.1% with fondaparinux and 6.0% with enoxaparin (p = 0.95 for the comparison of all three groups). Our study confirmed the effectiveness and safety of mechanical thromboprophylaxis without the use of anticoagulant drugs after total hip replacement in Japanese patients

We performed a meta-analysis of modern total joint replacement (TJR) to determine the post-operative mortality and the cause of death using different thromboprophylactic regimens as follows: 1) no routine chemothromboprophylaxis (NRC); 2) Potent anticoagulation (PA) (unfractionated or low-molecular-weight heparin, ximelagatran, fondaparinux or rivaroxaban); 3) Potent anticoagulation combined (PAC) with regional anaesthesia and/or pneumatic compression devices (PCDs); 4) Warfarin (W); 5) Warfarin combined (WAC) with regional anaesthesia and/or PCD; and 6) Multimodal (MM) prophylaxis, including regional anaesthesia, PCDs and aspirin in low-risk patients. Cause of death was classified as autopsy proven, clinically certain or unknown. Deaths were grouped into cardiopulmonary excluding pulmonary embolism (PE), PE, bleeding-related, gastrointestinal, central nervous system, and others (miscellaneous). Meta-analysis based on fixed effects or random effects models was used for pooling incidence data. In all, 70 studies were included (99 441 patients; 373 deaths). The mortality was lowest in the MM (0.2%) and WC (0.2%) groups. The most frequent cause of death was cardiopulmonary (47.9%), followed by PE (25.4%) and bleeding (8.9%). The proportion of deaths due to PE was not significantly affected by the thromboprophylaxis regimen (PA, 35.5%; PAC, 28%; MM, 23.2%; and NRC, 16.3%). Fatal bleeding was higher in groups relying on the use of anticoagulation (W, 33.8%; PA, 9.4%; PAC, 10.8%) but the differences were not statistically significant. Our study demonstrated that the routine use of PA does not reduce the overall mortality or the proportion of deaths due to PE

In order to compare the effect of oral apixaban (a factor Xa inhibitor) with subcutaneous enoxaparin on major venous thromboembolism and major and non-major clinically relevant bleeding after total knee and hip replacement, we conducted a pooled analysis of two previously reported double-blind randomised studies involving 8464 patients. One group received apixaban 2.5 mg twice daily (plus placebo injection) starting 12 to 24 hours after operation, and the other received enoxaparin subcutaneously once daily (and placebo tablets) starting 12 hours (± 3) pre-operatively. Each regimen was continued for 12 days (± 2) after knee and 35 days (± 3) after hip arthroplasty. All outcomes were centrally adjudicated. Major venous thromboembolism occurred in 23 of 3394 (0.7%) evaluable apixaban patients and in 51 of 3394 (1.5%) evaluable enoxaparin patients (risk difference, apixaban minus enoxaparin, -0.8% (95% confidence interval (CI) -1.2 to -0.3); two-sided p = 0.001 for superiority). Major bleeding occurred in 31 of 4174 (0.7%) apixaban patients and 32 of 4167 (0.8%) enoxaparin patients (risk difference -0.02% (95% CI -0.4 to 0.4)). Combined major and clinically relevant non-major bleeding occurred in 182 (4.4%) apixaban patients and 206 (4.9%) enoxaparin patients (risk difference -0.6% (95% CI -1.5 to 0.3)).

Apixaban 2.5 mg twice daily is more effective than enoxaparin 40 mg once daily without increased bleeding.

The aim of this study was to identify the incidence of post-operative symptomatic deep-vein thrombosis (DVT), as well as the risk factors for and location of DVT, in 665 patients (701 ankles) who underwent primary total ankle replacement. All patients received low-molecular-weight heparin prophylaxis. A total of 26 patients (3.9%, 26 ankles) had a symptomatic DVT, diagnosed by experienced radiologists using colour Doppler ultrasound. Most thrombi (22 patients, 84.6%) were localised distally in the operated limb. Using a logistic multiple regression model we identified obesity, a previous venous thromboembolic event and the absence of full post-operative weight-bearing as independent risk factors for developing a symptomatic DVT.

The incidence of symptomatic DVT after total ankle replacement and use of low-molecular-weight heparin is comparable with that in patients undergoing total knee or hip replacement.

Aims. Venous thromboembolism (VTE) is a potential complication of foot and ankle surgery. There is a lack of agreement on contributing risk factors and chemical prophylaxis requirements. The primary outcome of this study was to analyze the 90-day incidence of symptomatic VTE and VTE-related mortality in patients undergoing foot and ankle surgery and Achilles tendon (TA) rupture. Secondary aims were to assess the variation in the provision of chemical prophylaxis and risk factors for VTE. Methods. This was a multicentre, prospective national collaborative audit with data collection over nine months for all patients undergoing foot and ankle surgery in an operating theatre or TA rupture treatment, within participating UK hospitals. The association between VTE and thromboprophylaxis was assessed with a univariable logistic regression model. A multivariable logistic regression model was used to identify key predictors for the risk of VTE. Results. A total of 13,569 patients were included from 68 sites. Overall, 11,363 patients were available for analysis: 44.79% were elective (n = 5,090), 42.16% were trauma excluding TA ruptures (n = 4,791), 3.50% were acute diabetic procedures (n = 398), 2.44% were TA ruptures undergoing surgery (n = 277), and 7.10% were TA ruptures treated nonoperatively (n = 807). In total, 11 chemical anticoagulants were recorded, with the most common agent being low-molecular-weight heparin (n = 6,303; 56.79%). A total of 32.71% received no chemical prophylaxis. There were 99 cases of VTE (incidence 0.87% (95% CI 0.71 to 1.06)). VTE-related mortality was 0.03% (95% CI 0.005 to 0.080). Univariable analysis showed that increased age and American Society of Anesthesiologists (ASA) grade had higher odds of VTE, as did having previous cancer, stroke, or history of VTE. On multivariable analysis, the strongest predictors for VTE were the type of foot and ankle procedure and ASA grade. Conclusion. The 90-day incidence of symptomatic VTE and mortality related to VTE is low in foot and ankle surgery and TA management. There was notable variability in the chemical prophylaxis used. The significant risk factors associated with 90-day symptomatic VTE were TA rupture and high ASA grade. Cite this article: Bone Joint J 2024;106-B(11):1249–1256

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 aim of this study was to investigate the incidence, risk factors, and outcome of venous thromboembolism (VTE) following anterior cruciate ligament (ACL) reconstruction in a nationwide cohort. Patients and Methods. All ACL reconstructions, primary and revision, that were recorded in the Swedish Knee Ligament Register (SKLR) between 2006 and 2013 were linked with data from the Swedish National Board of Health and Welfare. The incidence of VTE was determined by entries between the day of surgery until 90 days postoperatively based on diagnosis codes and the prescription of anticoagulants. Risk factors, outcome, and the use of thromboprophylaxis were analyzed. Descriptive statistics with multivariate analysis were used to describe the findings. Results. The cohort consisted of 26 014 primary and revision ACL reconstructions. There were 89 deep venous thromboses (DVTs) and 12 pulmonary emboli (PEs) with a total of 95 VTEs (0.4 %). Six patients with a PE had a simultaneous DVT. The only independent risk factor for VTE was age greater than or equal to 40 years (odds ratio 2.31, 95% confidence interval 1.45 to 3.70; p < 0.001). Thromboprophylaxis was prescribed to 9461 patients (36%) and was equally distributed between those with and those without a VTE (37.9% vs 36.4%). All patient-reported outcome measures (PROMs) one and two years postoperatively were significantly lower in those with VTE. Conclusion. The incidence of VTE following ACL reconstruction is 0.4%, and the only significant risk factor is age. Patients with VTE had worse postoperative clinical outcome than patients without VTE. We recommend against the routine use of thromboprophylaxis, but it should be considered in older patients