Introduction. Air travel and total joint arthroplasty are both established risk factors for development of venous thromboembolism (VTE); accordingly patients are typically counseled against flying in the early postoperative period. The basis for this recommendation may be unfounded, as the risk of VTE associated with flying in the early postoperative period has not been investigated. Methods. This is a case-control study of 1465 consecutive unilateral total hip arthroplasties (THA) and total knee arthroplasties (TKA) performed by a single surgeon over an 18-month period. A multimodal regimen was used for VTE prophylaxis, consisting of early mobilization, mechanical prophylaxis, and chemoprophylaxis according to a risk-stratification model; 96% of patients received aspirin as the sole chemoprophylactic agent. The study population consisted of 220 patients (15.0%) who flew at a mean of 2.9 days after surgery. Patients who elected to fly were encouraged to wear anti-embolic stockings, perform frequent ankle-pump exercises, and move around at least every hour. Mean flight duration was 2.7 hours (range, 1.1 to 13.7 hours). This study population was compared to a control population of 1245 patients (85.0%) who did not fly during this time. Baseline characteristics were similar between the groups, with the exception that the group who flew tended to be older (65.5 vs. 59.5 years, p < 0.001) with a lower body-mass index (28.4 vs. 31.1 kg/m. 2. , p < 0.001). Results. Differences in the rates of DVT, PE, or overall VTE were not statistically significant between the groups. Symptomatic deep vein thrombosis (DVT) occurred in 2 patients (0.91%) in the study group compared with 5 patients (0.40%) in the control group. Symptomatic pulmonary embolism (PE) occurred in 1 patient in the study group (0.45%) compared with 10 patients in the study group (0.80%). Mean flight time among the three patients who developed symptomatic VTE was 2.3 hours (range, 1.4 to 3.7 hours). Conclusion. Using a multimodal approach to prophylaxis with an emphasis on early mobilization, the rate of symptomatic VTE was very low among patients who flew during the early postoperative period following THA and TKA, and was not increased over the control population who did not fly. Although there may be some degree of self-selection bias among patients who choose to fly after surgery, allowing them to do so appears to a safe practice

Introduction. VTE is a possible complication of foot and ankle surgery, however there is an absence of agreement on contributing risk factors in the development of VTE. The primary outcome of this study was to analyse the 90-day incidence of symptomatic VTE following foot and ankle surgery and to determine which factors may increase the risk of VTE. Methods. This was a national, multi-centre prospective audit spanning a collection duration of 9 months (2022/2023). Primary outcomes included incidence of symptomatic VTE and VTE related mortality up to 90 days following foot and ankle surgery and Achilles tendon rupture, and analysis of risk factors. Results. In total 11,363 patients were available for analysis. 5,090 patients (44.79%) were elective procedures, 4,791 patients (42.16%) were trauma procedures (excluding Achilles ruptures), 398 patients (3.50%) were acute diabetic procedures, 277 patients (2.44%) were Achilles ruptures undergoing surgery and 807 patients (7.10%) were Achilles ruptures treated non-operatively. There were 99 cases of VTE within 90 days of admission across the whole group (Total incidence = 0.87%), with 3 cases of VTE related mortality (0.03%). On univariate analysis, increased age and ASA grade showedhigher odds of 90-day VTE, as did previous cancer, stroke, history of VTE, and type of foot and ankle procedure / injury (p<0.05). However, on multivariate analysis, the only independent predictors for 90-day VTE were found to be the type of foot and ankle procedure (Achilles tendon rupture = Odd's Ratio 11.62, operative to 14.41, non-operative) and ASA grade (grade III/IV = Odd's Ratio 3.64). Conclusion. The incidence of 90-day post procedure VTE in foot and ankle surgery in this national audit was low. Significant, independent risk factors associated with the development of 90-day symptomatic VTE were Achilles tendon rupture management and high ASA grade

Introduction. Total contact casting (TCC) is one of the most commonly utilized modalities in the management of diabetic feet. We undertook a retrospective review to determine the prevalence of symptomatic VTE events in patients treated in a weight bearing TCC in our diabetic foot unit, and to formulate guidelines for VTE prophylaxis. Methods. Electronic records were reviewed to identify all patients treated in a TCC between 2014 and 2021. Data collection included patient demographics, comorbidities, period of immobilization in TCC, the incidence of VTE events, and any VTE prophylaxis prescribed during their period in TCC. Results. 549 patients were identified who had at least one episode of TCC. Mean age was 67 years (range 28 to 94 years) and the mean duration in cast was 10.2 weeks (range 0.3–46 weeks). Only 6 patients (1.1%) were prescribed chemical thrombo-prophylaxis during their period in TCC. Mean body mass index (BMI) for these patients was 32.3 (Range 18.4–58.9). Other significant comorbidities: 81% (n-444) of patients had associated cardio-vascular comorbidities; 54 % (n-296) had renal comorbidities including 22% (n-121) having had dialysis and 4.2% (n-23) with renal transplants. Eight of the 549 patients (1.5%) had suffered a VTE event of which only 2 (0.36%) were during the period of immobilization in TCC. One was a symptomatic DVT (0.18%) and the another was an asymptomatic (incidental) finding of pulmonary embolism (PE). There was no mortality related to the VTE episodes. Conclusion. NICE guidelines state that one should “Consider pharmacological VTE prophylaxis for patients with lower limb immobilization”. Our study finds that patients treated in a weight bearing TCC do not require routine pharmacological VTE prophylaxis, in spite of an extended period of lower limb immobilization and significant medical comorbidities

Prolonged bedrest in hospitalized patients is a major risk factor for venous thromboembolism (VTE), especially in high risk patients with hip fracture. Thrombelastography (TEG) is a whole blood viscoelastic hemostatic assay with evidence that an elevated maximal amplitude (MA), a measure of clot strength, is predictive of VTE in orthopaedic trauma patients. The objective of this study was to compare the TEG MA parameter between patients with hip fracture who were more mobile post-operatively and discharged from hospital early to patients with hip fracture with reduced mobility and prolonged hospitalizations post-operatively. In this prospective cohort study, TEG analysis was performed in patients with hip fracture every 24-hours from admission until post-operative day (POD) 5, then at 2- and 6-weeks post-operatively. Hypercoagulability was defined by MA > 65. Patients were divided into an early (within 5-day) and late (after 5-day) discharge group, inpatient at 2-weeks group, and discharge to MSK rehabilitation (MSK rehab), and long term care (LTC) groups. Two-sample t-test was used to analyze differences in MA between the early discharge and less mobile groups. All statistical tests were two-sided, and p-values < 0.05 were considered statistically significant. In total, 121 patients with a median age of 81.0 were included. Patients in the early discharge group (n=15) were younger (median age 64.0) and more likely to ambulate without gait aids pre-injury (86.7%) compared to patients in the late discharge group (n=105), inpatients at 2-weeks (n=48), discharged to MSK rehab (n=30), and LTC (n=20). At two weeks post-operative, the early discharge group was significantly less hypercoagulable (MA=68.9, SD 3.0) compared to patients in the other four groups. At 6-weeks post-operative, the early discharge group was the only group to demonstrate a trend towards mean MA below the MA > 65 hypercoagulable threshold (MA=64.4, p=0.45). Symptomatic VTE events were detected in three patients (2.5%) post-operatively. All three patients had hospitalizations longer than five days after surgery. In conclusion, our analysis of hypercoagulability secondary to reduced post-operative mobility demonstrates that patients with hip fracture who were able to mobilize independently sooner after hip fracture surgery, have a reduced peak hypercoagulable state. In addition, there is a trend towards earlier return to normal coagulation status as determined by the TEG MA parameter. Post-operative mobility status may play a role in determining individualized duration of thromboprophylaxis following hip fracture surgery. Future studies comparing TEG to clinically validated mobility tools may more closely evaluate the contribution of venous stasis due to reduced mobility on hypercoagulation following hip fracture surgery

Prolonged bedrest in hospitalized patients is a major risk factor for venous thromboembolism (VTE), especially in high risk patients with hip fracture. Thrombelastography (TEG) is a whole blood viscoelastic hemostatic assay with evidence that an elevated maximal amplitude (MA), a measure of clot strength, is predictive of VTE in orthopaedic trauma patients. The objective of this study was to compare the TEG MA parameter between patients with hip fracture who were more mobile post-operatively and discharged from hospital early to patients with hip fracture with reduced mobility and prolonged hospitalizations post-operatively. In this prospective cohort study, TEG analysis was performed in patients with hip fracture every 24-hours from admission until post-operative day (POD) 5, then at 2- and 6-weeks post-operatively. Hypercoagulability was defined by MA > 65. Patients were divided into an early (within 5-day) and late (after 5-day) discharge group, inpatient at 2-weeks group, and discharge to MSK rehabilitation (MSK rehab), and long term care (LTC) groups. Two-sample t-test was used to analyze differences in MA between the early discharge and less mobile groups. All statistical tests were two-sided, and p-values < 0.05 were considered statistically significant. In total, 121 patients with a median age of 81.0 were included. Patients in the early discharge group (n=15) were younger (median age 64.0) and more likely to ambulate without gait aids pre-injury (86.7%) compared to patients in the late discharge group (n=105), inpatients at 2-weeks (n=48), discharged to MSK rehab (n=30), and LTC (n=20). At two weeks post-operative, the early discharge group was significantly less hypercoagulable (MA=68.9, SD 3.0) compared to patients in the other four groups. At 6-weeks post-operative, the early discharge group was the only group to demonstrate a trend towards mean MA below the MA > 65 hypercoagulable threshold (MA=64.4, p=0.45). Symptomatic VTE events were detected in three patients (2.5%) post-operatively. All three patients had hospitalizations longer than five days after surgery. In conclusion, our analysis of hypercoagulability secondary to reduced post-operative mobility demonstrates that patients with hip fracture who were able to mobilize independently sooner after hip fracture surgery, have a reduced peak hypercoagulable state. In addition, there is a trend towards earlier return to normal coagulation status as determined by the TEG MA parameter. Post-operative mobility status may play a role in determining individualized duration of thromboprophylaxis following hip fracture surgery. Future studies comparing TEG to clinically validated mobility tools may more closely evaluate the contribution of venous stasis due to reduced mobility on hypercoagulation following hip fracture surgery

The aim of this study was to identify factors independently associated with symptomatic venous thromboembolism (VTE) following acute Achilles tendon rupture (ATR), and to suggest a clinical VTE risk assessment tool for patients with ATR. From 2010–2018, 984 consecutive adults (median age 47yrs, 73% male) sustaining an ATR were retrospectively identified. There were 95% managed non-operatively (below-knee cast 52%, n=507/984; walking boot 44%, n=432/984), with 5% (n=45/984) undergoing primary operative repair (<6wks). VTE was diagnosed using medical records and national imaging archives, reviewed at a mean of 5yrs (1–10) post-injury. Regression was performed to identify factors independently associated with VTE. Incidence of VTE within 90 days of ATR was 3.6% (n=35/984; deep vein thrombosis 2.1% [n=21/984], pulmonary embolism 1.9% [n=19/984]). Age ≥50yrs (adjusted OR [aOR] 2.3, p=0.027), personal history of VTE/thrombophilia (aOR 6.1, p=0.009) and family history of VTE (aOR 20.9, p<0.001) were independently associated with VTE. These non-modifiable risk factors were incorporated into a VTE risk assessment tool. 23% of patients developing VTE (n=8/35) had a relevant personal or family history, but incorporating age into the tool identified 69% of patients with VTE (n=24/35). Non weight-bearing ≥2wks after ATR was also independently associated with VTE (aOR 3.2, p=0.026). Age ≥50 years, personal history of VTE/thrombophilia and a positive family history were independently associated with VTE following ATR. Incorporating age into our suggested VTE risk assessment tool enhanced sensitivity in identifying at-risk patients. Early weight-bearing in an appropriate orthosis may be beneficial in VTE risk reduction

Rivaroxaban is a novel, oral, once-daily, direct Factor Xa inhibitor in advanced development for the prevention and treatment of venous thromboembolism (VTE). This study analysed the potential economic benefit attributable to the use of oral rivaroxaban relative to subcutaneous enoxaparin for extended VTE prophylaxis (35±4 days) after total hip replacement (THR). In RECORD1, rivaroxaban reduced the incidence of the composite primary efficacy endpoint (total VTE, including all-cause mortality) by 70%, compared with enoxaparin (p< 0.001). Symptomatic VTE occurred in 0.3% and 0.5% (p=0.22) of patients receiving rivaroxaban and enoxaparin, respectively. Major bleeding was low and similar in both groups: 0.3% and 0.1% (p=0.18), respectively. Potential savings associated with oral rivaroxaban were based on any reduction in the incidence of symptomatic VTE events, and reduced administration and monitoring costs. Analyses for both the US and the UK included only non-drug costs incurred by the healthcare sector. It was assumed that nurses spent 3 minutes/day administering enoxaparin and training patients to self-inject; assumed duration of hospital stay was 5 days. UK costs (based on the 2007 NICE Guidelines) also included full blood counts (FBCs) every 3 days, for up to 14 days, in patients receiving enoxaparin. Two analyses were performed: one assumed no difference in the occurrence of symptomatic VTE between treatments; the other assumed that the observed difference was real, but did not reach statistical significance. In the first analysis, assuming no difference in symptomatic VTE incidence, the total resource cost in the US was $46/patient for enoxaparin and $42.5/patient for rivaroxaban: a saving of $3.5/patient. For the UK, the total resource cost was £33/patient for enoxaparin and £7.5/per patient for rivaroxaban: a saving of £25.5/ patient. Savings were driven by reduced monitoring (FBCs) and administration costs. In the second analysis, assuming the observed difference in symptomatic VTE incidence was real, the US total resource cost was $57/patient for enoxaparin and $42.5/patient for rivaroxaban: a saving of $14.5/patient. For the UK, the total resource cost was £30/patients for enoxaparin and £7.5/patient for rivaroxaban: a saving of £22.5/patient. Savings were again driven by reduced monitoring and administration costs, and also reduced VTE incidence. Over 400,000 US patients undergo THR, and ~60,000 patients in England and Wales undergo THR annually. Thus, the potential cumulative cost savings with rivaroxaban are considerable

Introduction: The standard length of hospital stay after total hip arthroplasty (THA) can be as short as 4 days. However, the risk of venous thromboembolism (VTE) extends beyond this period of hospitalization. A pooled analysis of the RECORD1 and RECORD2 studies evaluated the efficacy, safety, and timing of events with rivaroxaban compared with enoxaparin for the prevention of VTE after THA. Methods: Patients (N=7,050) were randomized to receive oral rivaroxaban 10 mg once daily starting postoperatively (for 31–39 days) or subcutaneous enoxaparin 40 mg once daily starting preoperatively (for 31–39 days in RECORD1, and 10–14 days followed by placebo in RECORD2). The primary efficacy endpoint was the composite of symptomatic VTE and all-cause mortality. The safety endpoints were treatment-emergent major bleeding, major bleeding including surgical-site bleeding, major bleeding plus clinically relevant non-major (CRNM) bleeding, and any bleeding. The primary efficacy endpoint was assessed during treatment. The incidence and timing of the safety endpoints were assessed after the first dose of study medication and up to 2 days after the last dose. Results: Rivaroxaban significantly reduced the incidence of symptomatic VTE and all-cause mortality compared with enoxaparin regimens (0.44% vs 1.01%, respectively; p=0.006), with no significant differences in major bleeding (0.2% vs 0.09%; p=0.219) or the composite of major plus CRNM bleeding (3.23% vs 2.61%; p=0.141). Of the symptomatic VTE and all-cause mortality events, 73% and 86% occurred after day 4 with the rivaroxaban and enoxaparin regimens, respectively. For the composite of major plus CRNM bleeding, 48% and 33% of events occurred after day 4 with the rivaroxaban and enoxaparin regimens, respectively. Conclusion: Rivaroxaban significantly reduced symptomatic VTE and all-cause mortality after THA compared with the enoxaparin regimens, with no significant difference in bleeding events. Major plus CRNM bleeding was more likely to occur earlier than day 4, whereas the majority of symptomatic venous thromboembolic events occurred after day 4. These results highlight the relevance of extended duration of thromboprophylaxis after THA as most VTE events occur post-discharge

Introduction Recent changes in the management of hip fracture surgery patients may have resulted in changes in the epidemiology of venous thromboembolism (VTE). We aimed to determine the incidence of and predictive risk factors for symptomatic VTE and mortality, and the use of VTE prophylaxis, in hip fracture surgery patients. Methods Hip fracture surgery patients were enrolled in 525 hospitals in France between October 1 and November 30, 2002 in this prospective, multicenter, epidemiological study. VTE was assessed by a critical events committee at 3 months. Risk factors were identified using logistic regression. Results Data were from 6860 (97%) of 7019 enrolled patients. Median age was 82 years and 76% were women. 47% were femoral neck and 53% trochanteric or subtrochanteric fractures. All were operated on (osteosynthesis 57%, half prosthesis 35% and THR 8%). Prophylaxis with a low-molecular-weight heparin (LMWH) was administered perioperatively in 97.6% and for at least four weeks in 69.5% (median prophylaxis duration: 6 weeks). The rate of symptomatic VTE at 3 months was 1.34% (95% CI: 1.04– 1.64). There were 16 PE (rate 0.25%) and 3 were fatal. The rate of major bleeding was 1.2%. At 6 months, 1006 patients (14.7%) were dead. Significant risk factors for symptomatic VTE were: history of VTE (OR 2.9), induction of anesthesia until arrival in the recovery room > 2 hrs (OR 2.5), and varicose veins/post-thrombotic syndrome (OR 2.2). LMWH prophylaxis significantly reduced the risk of symptomatic VTE (OR 0.2). Significant predictive factors for mortality were: cancer (OR 2.3), surgical complications requiring re-intervention (OR 1.8), confusion before fracture (OR 1.8), ASA score ≥3 (OR 1.7), BMI ≤18 kg/m2 (OR 1.6), congestive heart failure (OR 1.6), atrial fibrillation (OR 1.6) and age > 80 years (OR 1.1). Conclusions Extended LMWH prophylaxis is applied widely after hip fracture surgery in France. The current rate of postoperative VTE is low. However, a major change in the care of these patients is needed because of the high mortality rate

Venous thromboembolic events (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), remain one of the most common complications following total joint arthroplasty. Reported rates of symptomatic VTE following THA and TKA range from 0.83% to 15% and 2% to 10%, respectively. Thus, VTE prophylaxis should be routinely administered following total joint arthroplasty. However, while orthopaedic surgeons have considerable flexibility regarding their VTE prophylaxis regimen, it remains unclear which is optimal. Patients at low risk of VTE may receive excessive anticoagulation and unnecessarily risk further perioperative morbidity (wound complications, bleeding) following total joint arthroplasty. With an evolving health care landscape, emphasis on complications and readmissions, and shorter inpatient hospitalizations, it is imperative that a VTE prophylaxis regimen is simple, effective, easy to monitor, and has high patient compliance. Mobile pneumatic compression devices (MCDs) have been used with greater frequency following total joint arthroplasty, with multiple reports demonstrating their effectiveness in VTE prevention with or without the addition of aspirin for chemical prophylaxis. The use of MCDs allows the avoidance of more aggressive anticoagulation in the majority of patients undergoing total joint arthroplasty, decreases the incidence of wound complications, and achieves a low overall incidence of symptomatic VTE. Future investigations are necessary to determine the necessity and impact of the addition of aspirin to the use of MCDs for VTE prophylaxis

Hypothesis. Pre-specified pooling of data from the four phase III RECORD studies was conducted to determine whether rivaroxaban significantly reduced the less-frequent clinical endpoint of symptomatic venous thromboembolism (VTE) and all-cause mortality after total hip or knee arthroplasty (THA or TKA, respectively), compared with standard North American and European enoxaparin regimens. Methods and analysis. Patients (n=12,729) received rivaroxaban 10 mg once daily or enoxaparin 40 mg once daily (RECORD1-3) or 30 mg 12-hourly (RECORD4). Thromboprophylaxis was administered for 31-39 days (RECORD1; THA) or 10-14 days (RECORD3 and 4; TKA). RECORD2 (THA) compared 31-39 days' rivaroxaban with 10-14 days' enoxaparin followed by placebo. The pre-specified primary efficacy endpoint in the pooled analysis (composite of symptomatic VTE and all-cause mortality) and adjudicated bleeding events were analysed in the day 12±2 active treatment pool, when all patients had received active drug, and total treatment duration pool, where subgroup analyses were performed. Results. In the day 12±2 active treatment pool, the primary efficacy endpoint occurred in 0.5% of patients receiving rivaroxaban versus 1.0% of patients receiving enoxaparin (p=0.001). Major bleeding occurred in 0.3% versus 0.2% patients respectively (p=0.18) and major plus clinically relevant non-major bleeding occurred in 2.9% versus 2.5% patients respectively (p=0.19). In the total treatment duration pool, rivaroxaban significantly reduced the primary efficacy endpoint compared with enoxaparin regimens 0.6% versus 1.3% patients (p< 0.001) with similar rates of major bleeding. Over the total treatment period, rivaroxaban consistently reduced the primary efficacy endpoint across the pre-specified subgroups (age, gender, body weight, creatinine clearance). Conclusion. Rivaroxaban significantly reduced the composite of clinically important symptomatic VTE and all-cause mortality after THA or TKA compared with subcutaneous enoxaparin regimens in the direct comparison day 12±2 active treatment pool, with no significant differences in bleeding events. These results suggest a positive benefit-risk profile for oral, once-daily rivaroxaban

Introduction: The risk of venous thromboembolism (VTE) remains a major concern beyond the standard period of hospitalization of about 4 days after total knee arthroplasty (TKA). A pooled analysis of the RECORD3 and RECORD4 studies evaluated the efficacy, safety, and timing of events with rivaroxaban compared with enoxaparin for the prevention of VTE after TKA. Methods: Patients (N=5,679) were randomized to receive oral rivaroxaban 10 mg once daily starting postoperatively or subcutaneous enoxaparin 40 mg once daily starting preoperatively (European Union regimen; RECORD3) or enoxaparin 30 mg every 12 hours starting postoperatively (North American regimen; RECORD4) for 10–14 days. The primary efficacy endpoint was the composite of symptomatic VTE and all-cause mortality, and this was analyzed over the treatment period. The safety endpoints were treatment-emergent major bleeding, major bleeding including surgical-site bleeding, major bleeding plus clinically relevant non-major (CRNM) bleeding, and any bleeding. The incidence and timing of the safety endpoints were assessed after the first dose of study medication and up to 2 days after the last dose. Results: Rivaroxaban significantly reduced symptomatic VTE and all-cause mortality compared with enoxaparin regimens (0.73% vs 1.71%, respectively; p=0.001) with no significant differences in major bleeding (0.62% vs 0.36%, p=0.185) or composite of major plus CRNM bleeding (3.13% vs 2.48%, p=0.145). The majority of venous thromboembolic events occurred after day 4 for both regimens (rivaroxaban: 70%; enoxaparin: 68%). For the composite of major plus CRNM bleeding events, 44% occurred after day 4 with rivaroxaban regimens and 38% occurred after day 4 with enoxaparin regimens. Conclusion: Rivaroxaban significantly reduced symptomatic VTE and all-cause mortality compared with enoxaparin regimens after TKA, with no significant difference in bleeding events between regimens. Major plus CRNM bleeding was more likely to occur before day 4, whereas the majority of symptomatic venous thromboembolic events occurred after day 4. These results highlight the importance of continuing thromboprophylaxis beyond the normal time of hospital discharge for TKA

Introduction: Four randomized, double-blind, phase III studies (RECORD1–4) investigated the oral, direct Factor Xa inhibitor rivaroxaban for the prevention of venous thromboembolism (VTE) after major orthopaedic surgery. Patients (N=12,729) were randomized to receive oral rivaroxaban 10 mg once daily or subcutaneous enoxaparin 40 mg once daily (RECORD1–3), or 30 mg twice daily (RECORD4). In RECORD1 and 2, patients undergoing total hip arthroplasty received rivaroxaban for 31–39 days. Enoxaparin was given for 31–39 days in RECORD1, 10–14 days followed by placebo in RECORD2. In RECORD3 and 4, patients undergoing total knee arthroplasty received prophylaxis for 10–14 days. After prophylaxis, all patients were followed up for a further 30–35 days. Rivaroxaban significantly reduced the incidence of the primary efficacy outcome for the individual studies (total VTE; composite of any deep vein thrombosis, non-fatal pulmonary embolism [PE] and all-cause mortality) compared with the enoxaparin regimens, with similar rates of major bleeding. Methods: A pre-specified pooled analysis of all four trials was performed on all randomized patients who received at least one dose of double-blind study medication to evaluate the effect of rivaroxaban on the composite of symptomatic VTE and all-cause mortality (primary outcome for pooled analysis), and bleeding. This outcome was analysed at day 12±2 in the active treatment pool (enoxaparin-controlled in all studies) and in the total study duration pool (including follow-up after treatment). Results: Rivaroxaban significantly reduced the incidence vs enoxaparin of the composite of symptomatic VTE and death (day 12±2: 0.47% vs 0.97%, respectively, p=0.001; total study duration: 0.81% vs 1.6%, respectively, p< 0.001) and the composite of PE and death (day 12±2: 0.19% vs 0.39%, respectively, p=0.049; total study duration: 0.47% vs 0.76%, respectively, p=0.039). The rates of major bleeding with the rivaroxaban and enoxaparin regimens were 0.34% and 0.21%, respectively, p=0.175 at day 12±2 and at total study duration were 0.44% and 0.27%, respectively, p=0.135. Rivaroxaban also reduced the composite of death, infarction, stroke, symptomatic VTE and major bleeding vs enoxaparin (total study duration: 1.6% vs 2.2%, respectively, p=0.006). Conclusion: Rivaroxaban reduced the composites of major clinical outcomes compared with enoxaparin regimens, with similar rates of major bleeding, in patients undergoing major orthopaedic surgery

Background. Despite the suggestion by Virchow in 1856 that thrombosis was the result of venous stasis, endothelial dysfunction and hypercoagulability there are some fundamental questions which remain to be answered. The published studies fail to provide specific details such as cast type and anatomical location of the thrombosis, but instead focus on the incidence of VTE and which chemical thromboprophylaxis is most effective. Previous studies of VTE in trauma patients have involved small numbers of patients and have not look at the risk medium to long term risk. Most importantly they have not looked at the site of the VTE. This makes interpretation of the link between cast and VTE even more complex. Methodology. We analysed 1479 consecutive trauma cast applications and the incidence of symptomatic VTE in the six months following the injury. The diagonosis, cast type and site of the VTE was recorded. Results. The overall incidence of DVT was 2.5% (2.2% distal and 0.3% proximal), 50% occured inthe first 3 weeks, the rest were between 6–13 weeks. The incidence of PE was 0.7%, there was 1 death due to PE. Achilles tendon injury was a statistically significant risk factor, there were no other conditions with a specific risk. There was no difference between above and below knee cast immobilisation. However all symptomatic DVTs occured in the casted leg. Discussion. This is the first study to look at long term VTE risk and the site of thrombosis, these findings have implications for VTE prophylaxis. It would appear that the risk of developing symptomatic VTE extends beyound the currently advised treatment period. It also suggests that venous stasis and endothelial damage are more important that hypercoagulability in the development of VTE after cast treatment for trauma. We recommend a programme of exercises within the cast to reduce this risk

On the basis of observations made in recent years, it can be inferred that the incidence of venous thromboembolism (VTE) in Japan is as high as that in Western countries. Since 2007, the use of fondaparinux for the prophylaxis of VTE following lower-limb orthopedic surgery has been approved for Japanese patients. This study was performed with an aim to investigate the safety and efficacy of fondaparinux for the prevention of VTE following hip surgery in Japanese patients. From June 2007 to August 2008, we evaluated 141 consecutive patients (148 hips; average age, 65.6) undergoing total hip replacement (THR), consisted of cementless minimally invasive surgery, and hip fracture surgery (HFS), consisted of open reduction and internal fixation or bipolar hemiarthroplasty. We mainly used 2.5 mg of fondaparinux for a period extending up to 14 days. We estimated the symptomatic VTE and asymptomatic deep-vein thrombosis (DVT) rates in patients by ultrasonography performed on preoperative and postoperative day 3. In addition, we evaluated the pre-operative and postoperative plasma D-dimer levels on days 3, 7, and 14. We determined that both the preoperative and postoperative incidence of symptomatic VTE was 0%. A D-dimer value of 20 ug/ml or higher was not observed on preoperative days 3 and 7; however, this value was observed in 2 hips on postoperative day 14. The incidence of asymptomatic DVT was observed to be 0.8% preoperatively and 4% postoperatively. In particular, the corresponding value following HFS was observed to be 7.7% preoperatively. The incidence of the hemorrhagic event was observed to be 14.9%. Bleeding was mostly observed in the surgical and drainage areas. An overall major bleeding incidence of 0.7% (1 patient) was observed. The corresponding value in patients in whom the administration of fondaparinux was discontinued by day 14 was 18.9%. The study results indicate that fondaparinux is useful in Japanese patients for the prevention of VTE following hip surgery. However, the administration of this drug should be accompanied by additional measures to prevent the associated side effect of bleeding

Introduction. Venous thromboembolism (VTE) is a significant cause of patient morbidity and mortality, the risk of which increases in orthopaedic patients with lower limb immobilisation. This incidence should in theory reduce if the patients are ambulatory early in the treatment phase. The aim of this study was, therefore, to identify a difference in the incidence of symptomatic VTE by treating acute Achilles tendon rupture patients with conventional non-weight bearing plaster versus functional weight bearing mobilisation. Methodology. The notes of 91 consecutive patients with acute Achilles tendon rupture were retrospectively reviewed and prospectively followed. The patients' demographics, treatment modality (non-weight bearing plaster versus weight bearing boot), and the type of plaster immobilisation was compared to assess whether they affect the incidence of clinical VTE. The predisposing risk factors were also analysed between the treatment groups. Out of 91 patients, 50 patients with acute Achilles tendon rupture were treated conservatively in a conventional non-weight bearing immobilisation cast. From these 50 patients, 3 then underwent surgery and were therefore excluded from the results. On the other hand, 41 patients were treated with functional weight bearing mobilisation (Vacupad). Patients who did have a symptomatic thromboembolic event also had an ultrasound scan to confirm a deep vein thrombosis of the lower limb or a CT-scan to confirm pulmonary embolism. Results. Out of the 47 patients who were treated conservatively in a non-weight bearing plaster cast, 9 patients had a thromboembolic event (19.1%). On the other hand, out of the 41 patients who were treated with functional weight bearing mobilisation, only 2 patients had a symptomatic thromboembolic event (4.2%). This was statistically significant (p=0.012). This shows that patients who are treated in a non-weight bearing plaster have about five times increased risk of developing a sypmptomatic VTE compared to those treated by functional weight bearing mobilisation. There was however no difference in the predisposing factors in patients who developed VTE compared to those who did not. Conclusion. The incidence of symptomatic VTE after acute Achilles tendon rupture is high and under-recognised. Asymptomatic VTE after this injury is probably even higher. There is a significant decrease in the clinical incidence of thromboembolic events in patients treated conservatively with early mobilisation in the functional weight bearing boot compared to those treated in a non-weight bearing cast. There is a need for further research to define the possible benefit of thromboprophylaxis in patients treated by non-weight bearing plasters

Introduction: Rivaroxaban is a novel, oral, direct Factor Xa inhibitor in advanced clinical development for the prevention and treatment of thromboembolic disorders. In this phase III trial, the efficacy and safety of thromboprophylaxis with rivaroxaban was compared with enoxaparin in patients undergoing total knee replacement (TKR). Methods: In RECORD3 – a randomized, double-blind trial – patients received rivaroxaban 10 mg 6–8 hours after surgery and once daily (od) thereafter, or enoxaparin 40 mg od beginning the evening before surgery; both were continued for 10–14 days. The primary efficacy outcome was the composite of any deep vein thrombosis (DVT), non-fatal pulmonary embolism (PE) and all-cause mortality. Secondary efficacy outcomes included major venous thromboembolism (VTE; the composite of proximal DVT, PE and VTE -related death) and symptomatic VTE. The primary safety outcome was major bleeding, and other safety outcomes included any on-treatment bleeding and haemorrhagic wound complications (the composite of excessive wound haematoma and surgical-site bleeding). Results: A total of 2531 patients were randomized; 2459 were eligible for inclusion in the safety population and 1702 for the modified intention-to-treat population. The primary efficacy outcome was reported in 9.6% of patients receiving rivaroxaban and 18.9% of patients receiving enoxaparin. This equated to a relative risk reduction of 49% (p< 0.001) with rivaroxaban compared with enoxaparin. The incidence of major VTE was also significantly reduced with rivaroxaban compared with enoxaparin (relative risk reduction 62%, p=0.016). The incidence of symptomatic VTE was significantly lower in the rivaroxaban group than in the enoxaparin group (p=0.005). Major bleeding rates were 0.6% and 0.5% in the rivaroxaban and enoxaparin groups, respectively, and rates of any on-treatment bleeding were 4.9% and 4.8%, respectively. The incidence of haemorrhagic wound complications was 2.1% in the rivaroxaban group and 1.9% in the enoxaparin group. Conclusions: Rivaroxaban was significantly more effective than enoxaparin for the prevention of VTE after TKR, with a similar safety profile. The oral, direct Factor Xa inhibitor rivaroxaban, given as a fixed, unmonitored dose, may have the potential to change clinical practice for thromboprophylaxis after TKR

Purpose: Rivaroxaban is a novel, oral, direct Factor Xa inhibitor in advanced clinical development for the prevention and treatment of thromboembolic disorders. RECORD3 was a phase III trial conducted to compare the efficacy and safety of oral rivaroxaban with subcutaneous enoxaparin for the prevention of venous thromboembolism (VTE) in patients undergoing total knee replacement (TKR). Method: In this randomized, double-blind trial, patients received rivaroxaban 10 mg once daily (od), or enoxaparin 40 mg od. Enoxaparin was initiated the evening before surgery, and rivaroxaban 6–8 hours after surgery; therapy continued for 10–14 days. The primary efficacy outcome was the composite of any deep vein thrombosis (DVT), pulmonary embolism (PE), and all-cause mortality. Secondary efficacy outcomes included major VTE (the composite of proximal DVT, PE, and VTE-related death) and symptomatic VTE. Major bleeding was the primary safety outcome. Other safety outcomes included any on-treatment bleeding and hemorrhagic wound complications (the composite of excessive wound hematoma and surgical-site bleeding). Results: A total of 2531 patients were randomized; 2459 were eligible for inclusion in the safety population and 1702 for the modified intention-to-treat population. The incidence of the primary efficacy outcome was significantly reduced with rivaroxaban compared with enoxaparin (relative risk reduction 49%, p< 0.001). Major VTE occurred in 1.0% and 2.6% of patients receiving rivaroxaban and enoxaparin, respectively (relative risk reduction 62%, p=0.016). The incidence of symptomatic VTE was significantly lower in the rivaroxaban group than in the enoxaparin group (p=0.005). Major bleeding rates were 0.6% and 0.5% in the rivaroxaban and enoxaparin groups, respectively, and rates of any on-treatment bleeding were 4.9% and 4.8%, respectively. The incidence of hemorrhagic wound complications was 2.1% in the rivaroxaban group and 1.9% in the enoxaparin group. Conclusion: Rivaroxaban was significantly more effective than enoxaparin for thromboprophylaxis after TKR. Importantly, the incidence of bleeding was low and similar in both groups. This is the first trial to demonstrate the efficacy and safety of a fixed, unmonitored regimen of an oral, direct Factor Xa inhibitor – rivaroxaban – for thromboprophylaxis after TKR

Purpose: Venous thromboembolism (VTE) after major orthopaedic surgery remains an important clinical problem. Convenient, oral antithrombotic agents that are both effective and safe could improve adherence to guidelines for VTE prophylaxis. Recently, the focus has been on the development of oral agents that target a single step in the coagulation cascade and Factor Xa is a pivotal step. Rivaroxaban is an oral, direct Factor Xa inhibitor. Four international phase III trials (the RECORD programme) were undertaken to investigate the safety and efficacy of once-daily rivaroxaban for thromboprophylaxis after major orthopaedic surgery. The results of RECORD3 showed that rivaroxaban was more effective than enoxaparin 40 mg once daily after total knee replacement (TKR), with a 48% risk reduction in VTE and all cause mortality. RECORD4 was designed to determine the efficacy and safety of 10 mg rivaroxaban od compared to 30 mg bid enoxaparin after total knee replacement (TKR). Method: This study randomized 3148 patients to either rivaroxaban (10 mg od started 6–8 hours after surgery) or enoxaparin (30 mg bid s.c. started 12–24 hours after surgery) for 10–14 days. The primary efficacy outcome was the composite of asymptomatic deep vein thrombosis (DVT) detected by mandatory, bilateral venography and symptomatic DVT, non-fatal pulmonary embolism (PE), and all-cause mortality up to day 13±4. Secondary outcomes included major VTE (composite of proximal DVT, non-fatal PE, and VTE-related death) and symptomatic VTE. Safety outcomes included on-treatment major and non-major bleeding. Results: Rivaroxaban provided a 31% relative risk reduction in the incidence of the primary efficacy outcome when compared to enoxaparin (6.9% vs 10.1%, respectively; p=0.012). The corresponding rates for major VTE were 1.2% and 2.0%, respectively (p=0.124) and for symptomatic VTE were 0.7% and 1.2%, respectively (p=0.187). There were no significant differences in bleeding incidence observed between rivaroxaban and enoxaparin (major bleeding: 0.7% vs 0.3%, respectively, p=0.110; clinically relevant non-major bleeding: 2.6% vs 2.0%, respectively, p=0.279). Conclusion: Rivaroxaban 10 mg od is the first oral thromboprophylactic agent to significantly reduce the incidence of VTE after TKR compared to enoxaparin 30 mg bid, with a similar, low rate of bleeding

Purpose: We conducted the first, multicentre, prospective cohort study to define the incidence of symptomatic venous thromboembolism (VTE) in patients with tibia and ankle fractures treated conservatively and relatively minor lower leg fractures. The reported incidence of deep vein thrombosis (DVT) using routine venography in patients with lower leg injury requiring cast immobilization is approximately 20–40%, which has lead to the routine use of anticoagulant prophylaxis for several weeks in many such patients. However the vast majority of venographically-detected DVTs are asymptomatic, distal thrombi whose clinical relevance is uncertain. Therefore venography is not the best outcome measure to assess the burden of clinically important VTE. Method: Consecutive patients with tibia and fibula fractures (treated non-operatively) and patella and foot fractures, (treated operatively or conservatively) were assessed for eligibility at 5 Ontario hospitals. Patients were enrolled after informed consent within 96 hours of injury and were followed prospectively, by telephone, at 2, 6 and 12 weeks. Those with major trauma, active cancer, and previous VTE were excluded. Thromboprophylaxis was not allowed. Education regarding symptoms of VTE was provided at study entry and patients were asked about VTE symptoms at follow up. Suspected VTE was investigated in a standardized manner. Results: From August 2002 to June 2005, 1200 patients were enrolled from 2446 consecutively screened patients. 98% of patients completed 3-month follow-up. The mean age was 45 years (16 to 93) and 60% were female. The most common fractures were fibular (39%) and most injuries were caused by falls (75%). 99 % of these fractures were unilateral. Most fractures did not require surgical repair (93%), and 82% of patients were immobilized by cast or splint for an average of 42 ±32 days. Overall, 7 patients had symptomatic, objectively confirmed VTE (2 proximal DVT, 3 calf DVT, 2 PE) with no fatal PE – an incidence of 0.6 % (95% CI 0.2 to 1.2). Conclusion: Symptomatic VTE is an infrequent complication after these fractures without thromboprophylaxis. Therefore routine thromboprophylaxis is neither warranted, nor likely to be cost-effective in these patients. This study also highlights the significant discrepancy between clinical endpoint studies and studies using venography