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Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_5 | Pages 55 - 55
1 Mar 2017
Nho J Suh Y Park J Lee Y Ha Y Koo K
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Introduction. Venous thromboembolism (VTE), including pulmonary embolism (PE) resulting from deep vein thrombosis (DVT), remains a well-known serious complication after femoral fractures. The low molecular heparin is widely used to prevent VTE. This study compared the effectiveness of VTE prevention between dalteparin and enoxaparin. Materials and Methods. From 2013 to 2014, we retrospectively recruited 712 patients who had femoral fractures with operative treatment. All patients receiving VTE chemoprophylaxis with perioperative period using dalateparin in Group 1(N=395) and enoxaparin in Group 2(N=317). The prophylactic dosing was determined using individual product labeling and identified as enoxaparin 40 mg every 12 hours and dalteparin 2500 international unit (IU) once daily, based on clinical practice guidelines. The prophylaxis was started at admission, and maintained during average 8.43.5 days after operation. The outcome including the incidence of clinically significant deep vein thrombosis, pulmonary embolism, perioperative bleeding and cost of drugs were evaluated between two groups. Results. The two study groups did not differ significantly in fracture type, age, gender, ASA score. The overall incidence of VTE is similar between two groups. However, the incidence of fatal PE is significantly lower in patients with dalteparin (Group 1: 4/395(1.00%), Group 2: 10/317(3.15%), p<0.001). And the overall cost of each group is significantly different between two groups (Group 1: average KRW 89,426, Group 2: average KRW 32,188, p<0.001). Conclusion. Both dalteparin and enoxaparin could be safely used without notable complications in VTE prophylaxis. However, dalteparin had more advantages for prevention of fatal PE, compared to enoxaparin in patients with femoral fractures with significant cost effectiveness


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_15 | Pages 291 - 291
1 Mar 2013
Okada Y Abe N Miyazawa S Furumatsu T Fujii M Ozaki T
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Introduction. In Japan, edoxaban has been used for the prevention of venous thromboembolism (VTE) after total knee arthroplasty (TKA) since June 2011. Edoxaban is an oral direct factor Xa inhibitor, expected to be more convenient for the postoperative treatment of TKA. Enoxaparin, a II and Xa inhibitor, was approved in Japan for the prevention of VTE in patients undergoing orthopedics surgery from 2008. In this study, the effect for the prevention of VTE after TKA was compared between these two drugs in Japanese patients. Patients and Methods. We studied 42 Japanese patients who underwent TKA from May 2011 to April 2012. The operations were performed under general anesthesia, continuous femoral nerve block, an air tourniquet, and using cements for implant fixation. These patients were divided in two groups, use of 30 mg edoxaban once daily (ED group), and use of 1000 IU of enoxaparin twice daily (EN group). The initial dose was administered between 12 and 21 hours after surgery. We compared the incidence of VTE, bleeding complications, D dimer levels, and hemoglobin (Hb) loss. The screening of VTE was performed by enhanced CT scan screening from the chest to the foot on postoperative day 5 or 6 in all patients. The bleeding complication was divided into major bleeding and minor bleeding with Japanese guideline for the prevention of VTE. D dimer levels and Hb levels were preoperatively and postoperative day 1, 3, 5, 7, and 14. The loss of Hb was calculated from preoperative Hb level minus lowest postoperative Hb level. Results. The following results is showed in the order as ED group, EN group. The incidence of VTE was 45%, 32%, that was higher in ED group (see figure 1). There were almost no differences between both groups about D dimer levels and Hb loss in follow up period (see figure 2, 3). There were no major bleeding in both groups. The incidence of minor bleeding were 20%, 32%, that was higher in EN group (see figure 4). Discussion. We compared the effect of edoxaban and enoxaparin for the prevention of VTE. These two drugs are different way of administration. Edoxaban is administered orally, on the other enoxaparin requires with hypodermic injection. Therefore edoxaban is expected to be more convenient and less complaints than enoxaparin for the prevention of VTE. However our study showed that the use of 30 mg edoxaban once daily was less efficacy than the use of enoxaparin 1000 IU twice daily. The bleeding complication was lower incidence in the edoxaban, thus consideration should be given to the administration dosage of edoxaban to Japanese patients


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_34 | Pages 60 - 60
1 Dec 2013
Frisch N Charters M Wessell N Sikora-Klak J Dobson C Yu S Silverton C Laker M Les C
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Purpose:. Starting February 2012, our institution changed from enoxaparin (Lovenox) to the Factor Xa inhibitor, rivaroxaban (Xarelto) for venous thromboembolism prophylaxis after primary total hip (THA) and total knee arthroplasty (TKA). The purpose of our study was to compare rates of venous thromboembolism and rates of major bleeding between these two medications when used for venous thromboembolism prophylaxis after primary THA and TKA. Methods:. A retrospective review was performed on 1795 patients who underwent THA or TKA at our institution between January 1, 2011 and December 31, 2012. Patients were excluded if they had a bilateral procedure, partial arthroplasty (hip hemiarthroplasty, unicompartmental knee arthroplasty), revision surgery, and cases designated as complex. Patients were excluded if they were on other anticoagulants (dabigatran, aspirin, clopidogrel, warfarin, heparin, fondaparinux), or if pre-operative creatinine was 1.2 or greater. After excluding these patients, there were 1089 patients included in the study. Chart review recorded demographics (age, gender), comorbidities (BMI, ASA, creatinine), surgery performed (primary THA or TKA), length of stay (LOS), venous thromboembolic events (deep venous thrombosis [DVT], pulmonary embolus [PE]), post-operative infections, and major bleeding events (stroke, post-operative bleeding requiring transfusion). Periprosthetic infection rates are also currently being reviewed. T-tests were used to compare continuous variables between treatment groups, and Chi-square tests were used to compare categorical variables between treatment groups (α = 0.05). Results:. There were 779 patients (71.5%) who received enoxaparin and 310 patients (28.5%) who received rivaroxaban during the study period. Demographics of the patients are presented in Table 1. A comparison of venous thromboembolism rates. Pre-operative creatinine was higher in the enoxaparin group (0.81 ± 0.19 vs. 0.72 ± 0.18, p < 0.001). With the numbers available for study, there were no demonstrable differences in DVT (p = 0.400, power = 0.125), PE (p = 0.679, power = 0.066), cerebrovascular events (p = 0.913, power = 0.049), or transfusion rates (p = 0.412, power = 0.121). Conclusion:. To our knowledge this is one of, if not the largest non-industry funded studies comparing these two medications. There were no statistically demonstrable differences between the enoxaparin and rivaroxaban groups in terms of venous thromboembolism or major bleeding complications


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_5 | Pages 72 - 72
1 Mar 2017
Park S Kang H Yang T
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Introduction. Embolism in total arthroplasty or hip fractures, coagulation disorders, such as a variety of ways for the prevention of complications of anticoagulation therapy with medication is being done well. The purpose of this study, a representative of the anticoagulation therapy with enoxaparin and drug rivaroxaban of coagulation tests performed in patients between the two groups was to determine whether statistically significant differences. Methods. 47 patients who underwent arthroscopic surgery were randomly divided into two groups to rivaroxaban and enoxaparin group, and we performed coagulation tests before and 5 days after arthroscopic surgery to two drugs groups in order to investigate about the difference in clotting capacity. Results. Preoperative coagulation tests coagulation tests before the item was not significantly different between the two groups. (p=0.584) 5 days after surgery, the coagulation tests coagulation tests performed on all items, rivaroxaban showed an increase in the anticoagulation activity Between the two groups showed statistically significant difference (p=0.001),. Discussion and Conclusion. Our results indicate that orthopaedic surgery can induce a lot of bleeding will be careful for use of rivaroxaban. Rivaroxaban(Xarelto®) showed more bleeding tendency than Enoxaparin(Clexane®). So we should take more attentions in postoperative care after Total Joint Arthroplasty


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXIX | Pages 89 - 89
1 Sep 2012
Marlow W Adam R Walker J Musthyala S
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Aims. This phase II safety study aimed to investigate the bleeding side effect profile in patients treated with Rivaroxaban as a new agent for venous thromboembolism (VTE) prophylaxis following hip or knee arthroplasty. Methods. A retrospective study of complications was conducted in 88 consecutive patients undergoing hip and knee arthroplasty at one centre. Patients received chemical and/or mechanical VTE prophylaxis according to local guidelines. Data was collected from notes and evaluated using Fisher's exact test and t-Test. Significance was determined if p< =0.05. The primary end-point was local wound site oozing or bleeding. Secondary end-points were drop in haemoglobin, drain output and infection. Results. 55 patients were treated with Rivaroxaban, 18 with mechanical prophylaxis only, 10 with Enoxaparin and 5 with aspirin, clopidogrel or warfarin. The Rivaroxaban cohort demonstrated a statistically significant amount of increased major bleeding (24% vs. 0% p=0.03) and wound oozing (27% vs. 0% p=0.02) when compared to patients treated with Enoxaparin. Compared to those treated with other methods of VTE prophylaxis, Rivaroxaban also significantly increased major bleeding (24% vs. 6% p=0.01) and wound oozing (27% vs. 12% p=0.03). The Rivaroxaban cohort demonstrated a significantly larger drop in haemoglobin compared to the combined non-Rivaroxaban group (3.0 vs. 2.4 g/dL p=0.04). There was no significant difference in drain volume or rate of infection between groups. Conclusions. Rivaroxaban appears to cause increased wound site bleeding in comparison to Enoxaparin and other methods of thromboembolism prophylaxis. Further use of Rivaroxaban at this centre was therefore discontinued; however, the small group sizes and retrospective non-randomised design of this study introduce bias and limit the reliability of its findings. Prospective randomised controlled trial focused on wound complications is required to eliminate selection and reporter biases


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XLI | Pages 15 - 15
1 Sep 2012
Hoffman R Naylor J Adie S Dave J
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Rivaroxaban is an oral anticoagulant which has the potential to replace subcutaneous Clexane in post operative prophylaxis of venous thromboembolism following knee replacement. Rivaroxaban has been shown to be at least equivalent to Enoxaparin in the prevention of deep venous thrombosis and pulmonary embolism with a similar rate of major bleeding. However, the morbidity associated with the new product has yet to be fully examined. Our own anecdotal evidence suggests that Rivaroxaban may be associated with poorer knee range of motion, and greater bruising and haemarthrosis. This pilot study aimed to compare these outcomes as well as knee pain and length of hospital stay in patients receiving Rivaroxaban and Enoxaparin following total knee replacement. A controlled before and after study with single blinding was performed. Patients in the ‘Before’ group were given Rivaroxaban (our current protocol). Patients treated in the “After’ group were subjected to our previous protocol (Enoxaparin). Patients were followed up to 6-weeks post surgery. Blinded assessors reviewed range of motion and wound outcomes using a photographic method. Swelling was measured using a standardized technique. Bleeding, pain and length of stay were prospectively recorded. Data analysis is due to be completed in April 2011. Complete results will be available after this time. Discussion: Rivaroxaban was introduced to lessen patient burden as oral administration is presumed to be more acceptable than self-injection of Enoxaparin. It is yet to be determined comprehensively whether the benefits of oral administration outweigh any associated risks. Surgeons must carefully consider the risks and benefits of their choice of venous thrombosis prophylaxis following total knee replacement


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_IV | Pages 76 - 76
1 Mar 2012
Tsiridis E Gamie Z Upadhyay N George M Hamilton-Baillie D Giannoudis P
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Surgery for pelvic or acetabular fractures carries a high risk of deep-vein thrombosis (DVT). Reports indicate that fondaparinux is a more effective thromboprophylactic agent than low molecular weight heparin (LMWH) after major orthopaedic surgery. We prospectively evaluated a new protocol for DVT prophylaxis using fondaparinux. Patients and methods. One hundred and eight patients with pelvic or acetabular fractures were randomised to receive either fondaparinux or enoxaparin. Specific review points included the primary end-point of clinical deep vein thrombosis (DVT) or pulmonary embolism (PE) and any evidence of adverse effects such as bleeding or allergic reactions. Results. Two patients that received enoxaparin were found to have a DVT (3%) and one patient died from a PE (1%). There was no documented DVT or PE in patients that received fondaparinux. The mean number of units of blood transfused was significantly higher in the enoxaparin group and this was significant post-operatively (p<0.05). The current study supports that post-operative fondaparinux, in patients with pelvic and acetabular fractures, is more effective and equally safe to enoxaparin


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXV | Pages 221 - 221
1 Jun 2012
Rose B Sindali K Soueid H Jeer C Saran D
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Introduction. Rivaroxaban is the first licensed oral direct inhibitor of factor Xa. Recent studies from the RECORD trials suggest rivaroxaban has superior efficacy compared to enoxaparin in preventing venous thromboembolism (VTE) with no significant increase in the major bleeding risk. Concerns remain regarding the incidence of minor bleeding, consequent delayed wound healing and subsequent risk of infection. The aim of this observational study was to assess the incidence of post-operative complications in patients receiving either rivaroxaban or enoxaparin thromboprophylaxis following elective hip and knee arthroplasty. Methods. 258 patients undergoing elective total hip or knee arthroplasty within one NHS Trust were included. 202 subjects (mean age 70.7 years ± 10.0, 43% male) received a daily dose of 10mg of oral rivaroxaban and 56 (mean age 70.9 years ± 9.8, 39% male) had a daily subcutaneous injection of 40 mg of enoxaparin as thromboprophylaxis. Endpoints included VTE (deep vein thrombosis and pulmonary embolism), haemorrhagic wound complications, hospital re-admission, requirement for blood transfusion, minor and major bleeding and death. Results. There were no significant differences in the incidence of deep vein thrombosis, requirement for blood transfusion and readmission rate between rivaroxaban and enoxaparin-treated patients. However, the incidence of minor bleeding (2.0% versus 0%) and haemorrhagic wound complications (4.9% versus 1.8%) were non-significantly higher in the rivaroxaban-treated group. There were no cases of pulmonary embolism, major bleeding or death in either group. Conclusion. Our experience with rivaroxaban in elective hip and knee arthroplasty showed no significant difference in the incidence of VTE or major bleeding. There was, however, a tendency to greater risk of minor bleeding and consequent delayed wound healing affecting both morbidity and delaying discharge. These may predispose patients to a higher risk of wound infection, and thus these issues require further large scale evaluation


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_15 | Pages 314 - 314
1 Mar 2013
Rocos B
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The introduction of direct thrombin inhibitors in arthroplasty surgery has reignited the debate on the risk of wound complications when using chemical thromboprophylaxis. It has been suggested that direct thrombin inhibitors might lead to an increased risk of systemic and operative site bleeding and wound sepsis when compared to low molecular weight heparin. In July 2009, departmental thromboprophylaxis policy for patients undergoing hip and knee replacement surgery (including revision) was changed from subcutaneous enoxaparin for the duration of inpatient stay to dabigatran for 10 days (knees) or 28 days (hips) unless contraindicated. In the 2 years prior to policy change, 1091 patients underwent hip or knee arthroplasty (Group A), with 1150 patients undergoing the same procedures in the 2 years following July 2009 (Group B). A minority of patients were already on warfarin (2% in group 1, 3% in group 2). This study presents a retrospective analysis of all patients who returned to theatre within 30 days of joint replacement surgery to assess whether the change in unit policy caused any discernible increase in bleeding-related complications. In group A, 20 / 1091 patients (1.8%) returned to theatre within 30 days. 9 were for reasons unrelated to thromboprophylaxis (mainly dislocated hips), 4 for gastrointestinal bleeding and 7 for wound complications (haematoma, wound breakdown, or infection). In group B, 22 / 1150 patients (1.9%) returned to theatre within 30 days. 13 were for unrelated reasons, 4 for gastrointestinal bleeding, and 5 for wound complications. One patient with a wound complication was on warfarin and therefore did not receive dabigatran. The lower wound complication rate in group B was not statistically different. This study, in a large heterogeneous group of patients, suggests that a change from enoxaparin to dabigatran does not increase the incidence of early infection, or the risk of bleeding at the operative site or the gastrointestinal tract


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_12 | Pages 32 - 32
1 Mar 2013
Rocos B Lankester B
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The introduction of direct thrombin inhibitors in arthroplasty surgery has reignited the debate on the risk of wound complications when using chemical thromboprophylaxis. It has been suggested that direct thrombin inhibitors might lead to an increased risk of systemic and operative site bleeding and wound sepsis when compared to low molecular weight heparin. In July 2009, departmental thromboprophylaxis policy for patients undergoing hip and knee replacement surgery (including revision) was changed from subcutaneous enoxaparin for the duration of inpatient stay to dabigatran for 10 days (knees) or 28 days (hips) unless contraindicated. In the 2 years prior to policy change, 1091 patients underwent hip or knee arthroplasty (Group A), with1150 patients undergoing the same procedures in the 2 years following July 2009 (Group B). A minority of patients were already on warfarin (2% in group 1, 3% in group 2). This study presents a retrospective analysis of all patients who returned to theatre within 30 days of joint replacement surgery to assess whether the change in unit policy caused any discernible increase in bleeding-related complications. In group A, 20/1091 patients (1.8%) returned to theatre within 30 days. 9 were for reasons unrelated to thromboprophylaxis (mainly dislocated hips), 4 for gastrointestinal bleeding and 7 for wound complications (haematoma, wound breakdown, or infection). In group B, 22/1150 patients (1.9%) returned to theatre within 30 days. 13 were for unrelated reasons, 4 for gastrointestinal bleeding, and 5 for wound complications. One patient with a wound complication was on warfarin and therefore did not receive dabigatran. The lower wound complication rate in group B was not statistically different. This study, in a large heterogeneous group of patients, suggests that a change from enoxaparin to dabigatran does not increase the incidence of local or systemic complications of sufficient severity to warrant return to theatre


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_9 | Pages 22 - 22
1 Feb 2013
Rocos B Lankester B
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The introduction of direct thrombin inhibitors in arthroplasty surgery has reignited the debate on the risk of wound complications when using chemical thromboprophylaxis. It has been suggested that direct thrombin inhibitors might lead to an increased risk of systemic and operative site bleeding and wound sepsis when compared to low molecular weight heparin. In July 2009, departmental thromboprophylaxis policy for patients undergoing hip and knee replacement surgery (including revision) was changed from subcutaneous enoxaparin for the duration of inpatient stay to dabigatran for 10 days (knees) or 28 days (hips) unless contraindidated. In the 2 years prior to policy change, 1091 patients underwent hip or knee arthroplasty (Group 1), with1150 patients undergoing the same procedures in the 2 years following July 2009 (Group 2). A minority of patients were already on warfarin (2% in group 1, 3% in group 2). This study presents a retrospective analysis of all patients who returned to theatre within 30 days of joint replacement surgery to assess whether the change in unit policy caused any discernible increase in bleeding-related complications. In group 1, 23/1091 patients (2.1%) returned to theatre within 30 days. 8 were for reasons unrelated to thromboprophylaxis (mainly dislocated hips), 5 for gastrointestinal bleeding (mainly upper GI endoscopy) and 10 for wound complications (haematoma, wound breakdown, or washout of early infection). In group 2, 22 / 1150 patients (1.9%) returned to theatre within 30 days. 12 were for unrelated reasons, 5 for GI bleeding, and 5 for wound complications. The lower return to theatre rate in the second group was not statistically different. This study, in a large heterogeneous group of patients, suggests that a change from enoxaparin to dabigatran does not increase the incidence of early infection, or the risk of bleeding at the operative site or the gastrointestinal tract


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_1 | Pages 166 - 166
1 Jan 2013
Buddhdev P Basu D Davies N Waters T
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Introduction. Rivaroxiban is a direct inhibitor of factor Xa, a licensed oral thromboprophylactic agent that is increasingly being adopted for lower limb arthroplasty. Rivaroxiban has been NICE-approved for use in primary hip and knee arthroplasty following the RECORD 4 trials; proving it more effective in preventing venous thrombo-embolic (VTE) events compared to enoxaparin. Enhanced Recovery Programmes (ERP) are designed to enable patients to recover quickly and return home safely within a few days. Methods. We prospectively studied 1223 patients (age- and sex-matched) who underwent lower-limb arthroplasty enrolled in our ERP between March 2010 and December 2011; 454 patients (Group 1) received enoxaparin, 769 patients (Group 2) received rivaroxiban. Patients wore thrombo-embolic stockings for six weeks post surgery. Patients were monitored for thrombo-embolic events and wound-related complications for 42 days post-operatively. Results. 1223 patients underwent lower-limb arthroplasty during our study period. There were similar numbers of THRs and TKRs in each group 230:224 and 370:399. Average length of stay was 4.9 days (range 1–19) in group 1 and 4.5 days (range 2–23) in group 2. The rate of VTE events was the same in both groups (< 1%). In group 1 (enoxaparin), 21(4.6%) of the 454 patients experienced oozing/infected wounds that required further surgical attention. In group 2 (rivaroxiban), 46 (6%) of the 769 patients had wound-related complications, of which 70% were in primary THR patients. Conclusion. Rivaroxabans use in clinical practice has been questioned concerning its wound-related complications. The RECORD 4 trial focused on major bleeding as the primary safety outcome, however we postulate slow post-operative oozing can lead to haematoma formation, increasing the risk of superficial wound and deep infections potentially requiring revision surgery. This study shows an increased wound complication rate in the Rivaroxiban group, highlighting the need for further clinical trials to assess its safety and efficacy


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_11 | Pages 18 - 18
1 Nov 2022
Dhaliwal S Yap R Gabr H Marson B Bidwai A Desai V
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Abstract. Introduction. Neck of femur (NOF) fracture patients are at risk of developing venous thromboembolisms (VTE). VTE risks could be reduced by adhering to the National Institute for Health and Care Excellence (NICE) recommendation for 1 month of prophylaxis with low molecular weight heparin. This audit aimed to assess and improve local compliance to national guidelines on VTE prophylaxis in NOF fracture patients following discharge. Methods. A retrospective consecutive case series of all NOF fractures treated at our institution from May – July 2021 was conducted. Those not eligible for outpatient VTE prophylaxis were excluded (anticoagulated for other indications, completed prophylactic course in hospital, inpatient death, pharmacological prophylaxis contraindicated). The agent and duration of VTE prophylaxis, and the occurrence of clinically significant VTE or bleeds were recorded. A re-audit was conducted in March 2022. Results. From May – July 2021, only 1/65 (1.5%) patient was discharged on a VTE prophylaxis regime consistent with NICE guidelines (1 enoxaparin, 56 rivaroxaban, 6 apixaban; 58 35-day course, 5 28-day course). A quick-guide document summarising the standard inpatient and outpatient VTE prophylaxis regimes for various orthopaedic indications was designed and widely disseminated. In March 2022, 30/34 (88.2%) patients were discharged with enoxaparin and 24/34 (70.6%) received a 28-day course. There were no cases of clinically significant VTE or bleeds in both cycles. Conclusion. Local compliance to national guidelines improved significantly with the implementation of a standardised VTE prophylaxis protocol. Our quick-guide document is a reproducible way of communicating consensus and ensuring consistency within a department


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXI | Pages 185 - 185
1 May 2012
W. DF M. RL B. IE S. DB F. M T. JB M. H T. W A. KK A. GGT
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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


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXI | Pages 184 - 184
1 May 2012
G. NS P. W D. M K. JM
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Background. Current treatments for the prevention of thromboembolism include heparin and low-molecular weight heparins (LMWHs). A number of studies have suggested that long term administration of these drugs may adversely affect osteoblasts and therefore, bone metabolism. Xarelto(tm) (Rivaroxaban) is a new anti-thrombotic drug for the prevention of venous thromboembolism in adult patients undergoing elective hip and knee replacement surgery. The aim of this in vitro study was to investigate the possible effects of rivaroxaban on osteoblast proliferation, function, matrix mineralisation and gene expression compared to enoxaparin, a commonly used LMWH. Methods. Primary human osteoblast cultures were treated with varying concentrations of rivaroxaban (0.013, 0.13, 1.3 and 13 μg/ml) or enoxaparin (0.1, 1.0 and 10 international units/ml). The effect of each drug on osteoblast function and matrix mineralisation was evaluated by measuring alkaline phosphatase activity and calcium deposition, respectively. The MTS assay was used to assess the effect of drug treatments on cell proliferation. Changes in osteocalcin, Runx2 and BMP-2 messenger RNA (mRNA) expression following drug treatments were measured by real-time polymerase chain reaction (PCR). Results. Rivaroxaban and enoxaparin treatment did not adversely affect osteoblast proliferation. However, both drugs caused a significant reduction in osteoblast function, as measured by alkaline phosphatase activity, with a moderate reduction in calcium deposition also observed. This reduction in osteoblast function was associated with a reduction in the mRNA expression of the bone marker, osteocalcin, the transcription factor, Runx2, and the osteogenic factor, BMP-2. Conclusion. These data show that rivaroxaban treatment may negatively affect bone through a reduction in osteoblast function. The increased duration of recommended Rivaroxaban therapy (2 and 5 weeks) post-arthroplasty compared to Enoxaparin therapy (average one week) may have a more pronounced effect on bone homeostasis


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_18 | Pages 1 - 1
1 Dec 2014
Luke C Kamalanathan S Doorgakant A Sanger R
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In recent years, many changes have taken place regarding agents used for chemical thromboprophylaxis in elective joint replacement. Enoxaparin, Rivaroxaban, Dabigatran and Apixaban are all now recommended in NICE CG92 and their use varies nationally. Whilst data exists comparing oral anticoagulants to Enoxaparin, there is little data on the comparative efficacy of the individual oral anticoagulants. This study analyses data from Warrington Hospital, where each of the above oral anticoagulants was used trustwide in 3 successive years following hip and knee arthroplasty. We analysed similar 4–5 month periods in 2010(Rivaroxiban), 2011(Dabigatran) and 2012(Apixaban). The study was done prospectively and data was collected contemporaneously. The total sample size was 475 patients. Data was collected through electronic hospital patient records. Patients were excluded if data was incomplete. We defined our primary outcome as any complication requiring the drug to be omitted or stopped. We found that for Rivaroxaban, 7 of 129 patients had the drug omitted or stopped (5.4%, 95% confidence interval 1.0–9.8), for Dabigatran 19 of 150 patients, (12.7%, 95% confidence interval 6.4–19.0) and for Apixaban 10 of 196 patients (5.1%, 95% confidence interval 0.9–9.3). For Rivaroxaban and Apixaban, there were no confirmed thromboembolic events; however, for Dabigatran, there were six VTEs. All three had bleeding complications, which were well below the figures published for Enoxaparin. Apixaban registered the lowest rate in our study (5.1%). This data suggests that Apixaban is a safe oral anticoagulant in elective total knee and hip replacement


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XLI | Pages 136 - 136
1 Sep 2012
Pohl A Solomon L
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Patients with pelvic and acetabular fractures have a high risk of developing thromboembolic complications. Despite routine screening, the risk of PE remains high and may develop in patients with negative DVT screening. The search for a means to identify the patient ‘at risk’ has been elusive. 537 consecutive patients, referred to Royal Adelaide Hospital over a 20 year period for treatment of pelvic and acetabular fractures, were evaluated prospectively for pulmonary embolus (PE). 352 patients referred directly to the author were treated with variable dose heparin as prophylaxis to venous thromboembolic (VTE) disease. 184 patients primarily admitted under the general surgeons or to ITU, prior to referral to the author, were treated with fixed dose heparin or Enoxaparin. All patients were followed prospectively to determine the rate of pulmonary embolus. The heparin dosage requirements of those who developed pulmonary emboli were compared to those who did not. Patients were also identified for whom a clinical diagnosis of deep venous thrombosis (DVT) was made during the study and their heparin dosage requirements were determined. 7 of 352 patients treated with variable dose heparin developed PE (1.98%). 13 of 184 patients treated with fixed dose heparin, Enoxaparin, or combinations, developed PE (7.06%). An incidental finding of DVT was made in 36 patients. Of these, 10 patients (2.8%) were treated with variable dose heparin and 26 patients (14.1%) with fixed dose heparin or Enoxaparin. The average Injury Severity Score was higher in patients treated with variable dose heparin than those treated with fixed dose regimes. Patients treated with variable dose heparin who developed PE showed a progressively increasing heparin requirement. The majority of patients who did not develop PE (72%) showed a progressively decreasing heparin requirement (suggesting reversal of a prothrombotic state). 21% showed an initial increasing heparin requirement followed by a decreasing requirement (suggesting a prothrombotic state that was reversed, e.g. a DVT successfully treated by the increasing heparin dose provided by a variable dose regime). 4% manifested a static heparin requirement (suggesting maintenance of a prothrombotic state). 8 patients treated with variable dose heparin developed DVT. 6/8 patients manifested a phase of progressively increasing heparin requirement, followed by a decreased requirement, and 2/8 patients manifested a sustained level of heparin requirement. Patients with pelvic and acetabular fractures treated with variable dose heparin showed a rate of PE (1.98%). This is remarkably low compared with published rates of PE in such patients, and particularly compared with those patients treated only with chemoprophylaxis. The rate of PE was 3.5x higher and the rate of DVT was 5x higher in patients treated with fixed dose heparin or Enoxaparin. Patients who developed PE or DVT manifested an increasing heparin requirement. An increasing dosage of heparin may protect the ‘at risk’ patient from venous thromboembolism. Fixed dose unfractionated heparin/LMWH may be insufficient to treat the ‘at risk’ patient. An increasing heparin requirement may identify the patient ‘at risk’


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_27 | Pages 3 - 3
1 Jul 2013
Kamalanathan S Luke C Doorgakant A Sanger R
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In recent years, many changes have taken place regarding agents used for chemical thromboprophylaxis in elective joint replacement. Enoxaparin, Rivaroxaban, Dabigatran and Apixaban are all now recommended in NICE CG92 and their use varies nationally. While data exist comparing oral anticoagulants to Enoxaparin, there is little data on the comparative efficacy of the individual oral anticoagulants. This study analyses data from Warrington Hospital, where each of the above oral anticoagulants was used trustwide in 3 successive years following hip and knee arthroplasty. We analysed similar 4–5 month periods in 2010 (Rivaroxiban), 2011 (Dabigatran) and 2012 (Apixaban). The study was done prospectively and data was collected contemporaneously. The total sample size was 475 patients. Data was collected through electronic hospital patient records. Patients were excluded if data was incomplete. We defined our primary outcome as any complication requiring the drug to be omitted or stopped. We found that for Rivaroxaban, 7 of 129 patients had the drug omitted or stopped (5.4%, 95% confidence interval 1.0–9.8), for Dabigatran 19 of 150 patients, (12.7%, 95% confidence interval 6.4–19.0) and for Apixaban 10 of 196 patients (5.1%, 95% confidence interval 0.9–9.3). For Rivaroxaban and Apixaban, there were no confirmed thromboembolic events; however, for Dabigatran, there were six VTEs. All three had bleeding complications, which were well below the figures published for Enoxaparin. Apixaban registered the lowest rate in our study (5.1%). This data suggests that Apixaban is a safe oral anticoagulant in elective total knee and hip replacement


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_1 | Pages 167 - 167
1 Jan 2013
Morris C Kumar V Sharma S Morris M Raut V Kay P
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Financial impact and patient satisfaction with four different anticoagulants for hip and knee arthroplasty in patients with a previous history of VTE- A prospective randomised trial. Introduction. New generation oral anticoagulants (dabigatran/rivaroxaban) have recently become available for the prevention of venous thromboembolism (VTE) following hip and knee arthroplasty. Traditional therapies (warfarin/low molecular weight heparins) are less costly, but have several limitations. The aim of this study was to evaluate the financial impact of substituting enoxaparin and warfarin with newer therapies dabigatran and rivaroxaban. A secondary objective was to investigate patient satisfaction with these treatments. Methods. A randomised prospective study was conducted over a 12 month period. Patients with a history of VTE undergoing hip or knee replacement were randomised to receive one of four anticoagulants for five weeks post surgery. Information was gathered during the hospital stay and then post discharge, by telephone, for five weeks(35 days)to determine costs. The costs included cost of drug, nursing time, blood monitoring and transport costs. The patients were also asked to complete the Duke Anticoagulation Satisfaction Scale (DASS). The DASS is a 26 item questionnaire which has 7 responses for each question. Results. Although dabigatran and rivaroxaban had higher drug acquisition costs, warfarin and enoxaparin were financially more costly overall. These additional costs were mainly due to increased blood monitoring and time for training and administration which is not required for newer therapies. DASS scores were significantly better with dabigatran (38.5±5.1) and rivaroxaban (38.6±8.3) compared to warfarin (71.8±16.2) and enoxaparin (68.5±14.2) (p< 0.001). This indicates more satisfaction for patients prescribed dabigatran or rivaroxaban compared to traditional therapies. Conclusion. The use of new generation oral anticoagulants has the potential to significantly reduce the financial burden of thromboprophylaxis on the NHS with an additional benefit of better patient satisfaction when compared to traditional therapies


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_1 | Pages 129 - 129
1 Jan 2013
Shah S Meakin R Nisar A McGregor-Riley J Gibson R
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Background. Venous thromboembolism (VTE) is a common complication of pelvic and acetabular fracture fixation. There is, however, currently limited data to guide clinical decisions on thromboprophylaxis choice in these patients. Methods. This is a prospective study with retrospective analysis of all the patients who were admitted to the Northern General Hospital between August 2009 and March 2011. 2 consultants using same technique and peri-operative regime carried out all procedures. All patients were administered prophylactic enoxaparin and those who were admitted via another hospital had a pre-operative Doppler scan. Post-operatively all patients were commenced on warfarin, or low molecular weight heparin (enoxaprin) if warfarin was contra-indicated, and was continued for three months after discharge. Results. Eighty-nine patients were admitted during this period of which 25 were treated conservatively and were excluded from the study. The mean age of patients was 39.7 years (range 17 to 83) & 73% of those were men. 65% were involved in RTA and 49% had more than one injury. 46 patients were transferred from another hospital. Of those 3 had DVT confirmed on Dopplers and had IVC filters inserted preoperatively. 52 patients were treated with warfarin and 12 with Clexane. Two patients had warfarin related complications (thigh haematoma and small subdural haematoma). Both were treated conservatively and made a full recovery. Two of the warfarin-treated (3.8%) and one of enoxaparin-treated (8%) patients developed DVT/PE. One of the two warfarin-treated patients had a PE despite having an INR of 4.2 and the other patient upon transferring to local hospital had his warfarin stopped prematurely. Conclusions. The study shows that preoperative enoxaparin followed by postoperative warfarin is an effective thromboprophylaxis regime and is associated with low complication rate