Objectives. Venous thromboembolism (VTE) is a major potential complication following orthopaedic surgery. Subcutaneously administered enoxaparin has been used as the benchmark to reduce the incidence of VTE. However, concerns have been raised regarding the long-term administration of enoxaparin and its possible negative effects on bone healing and bone density with an increase of the risk of osteoporotic fractures. New oral anticoagulants such as rivaroxaban have recently been introduced, however, there is a lack of information regarding how these drugs affect bone metabolism and post-operative bone healing. Methods. We measured the migration and proliferation capacity of mesenchymal stem cells (MSCs) under enoxaparin or rivaroxaban treatment for three consecutive weeks, and evaluated effects on MSC mRNA expression of markers for stress and osteogenic differentiation. Results. We demonstrate that enoxaparin, but not rivaroxaban, increases the migration potential of MSCs and increases their cell count in line with elevated mRNA expression of C-X-C chemokine receptor type 4 (CXCR4), tumor necrosis factor alpha (TNFα), and alpha-B-crystallin (CryaB). However, a decrease in early osteogenic markers (insulin-like growth factors 1 and 2 (IGF1, IGF2), bone morphogenetic protein2 (BMP2)) indicated inhibitory effects on MSC differentiation into osteoblasts caused by enoxaparin, but not by rivaroxaban. Conclusions. Our findings may explain the adverse effects of enoxaparin treatment on bone healing. Rivaroxaban has no significant impact on MSC metabolism or capacity for osteogenic differentiation in vitro. Cite this article: Dr H. Pilge. Enoxaparin and rivaroxaban have different effects on human mesenchymal stromal cells in the early stages of bone healing. Bone Joint Res 2016;5:95–100. DOI: 10.1302/2046-3758.53.2000595

Newer irreversible oral anticoagulants such as rivaroxaban, a direct factor 10a inhibitor, are increasingly employed to prevent thromboembolic events in atrial fibrillation (AF) patients, and to manage venous thromboembolism (VTE). Unlike warfarin, these agents require no monitoring and involve infrequent dose adjustment. We report the case of a patient treated with rivaroxaban for AF. Patient presented with unprovoked sudden onset right shoulder pain which clinically resembled shoulder haemarthrosis. A single case was anonymised and retrospectively reviewed through examination of clinical and radiographic data. A 70 year old female with known AF presented to Accident and Emergency with sudden onset of right shoulder pain and limited movement, which developed over one hour. The pain was constant, localised to the shoulder and without trauma. Past medical history included severe aortic regurgitation and associated thoracic aortic aneurysm, heart failure, atrial fibrillation and hypertension. Observations were normal upon admission with no haemodynamic compromise or pyrexia. Examining the right shoulder demonstrated distension of shoulder joint capsule, tenderness and a reduced range of movement. Temperature and neurovascular status in the right arm were normal. Investigations upon admission included an INR of 1.2. An anteroposterior right shoulder radiograph showed no evidence of fracture. Patient was managed conservatively with simple oral analgesia. Importantly, rivaroxaban was withheld for 5 days and symptoms resolved. Warfarin therapy was subsequently commenced instead as treatment for AF. Patient was discharged one week later and seen in clinic two weeks post-discharge. A full recovery occurred and with a full range of movement in the right shoulder. In the UK, current National Institute for Health and Care Excellence (NICE) guidelines recommend the use of factor 10a inhibitors, for prevention of stroke in AF patients, and following elective total hip and knee replacement operations to prevent VTE. In turn, rivaroxaban is increasingly prescribed as first line therapy. Whereas warfarin has a documented association with haemarthrosis, there is no primary literature evaluating the incidence of factor 10a therapy associated haemarthrosis. In our case, the unprovoked shoulder haemarthrosis resolved following rivaroxaban cessation. In comparison with warfarin, rivaroxaban is irreversible. With warfarin and a high INR, vitamin K can be used to reverse the anticoagulation. There is no equivalent for rivaroxaban. We suggest further studies into incidence of haemarthrosis associated with oral anticoagulant therapy be undertaken, and treating physicians be aware of such complication

Background. Hitherto, no study has compared blood loss (BL) after different thromoprophylactic regimes (TR). The objective of this study was to quantify and compare BL in total hip arthroplasty (THA) under three different TRs. Methods. Between September 2013 and July 2014, sixty primary, unilateral, same-implant THAs entered a randomised, double-blind clinical trial. The patients were randomised to receive manufacturers' recommended doses of enoxaparin, dabigatran or rivaroxaban. Complete blood counts were obtained preoperatively and on the third day postoperatively. BL was calculated according to the Nadler formula. We also evaluated the occurence of wound healing disturbances (WHDs). All data were analysed using R statistical software. Results. The mean BL and standard deviations were 844 ± 222 ml for enoxaparin, 854 ± 205 ml for dabigatran and 806 ± 227 ml for rivaroxaban. The BL did not significantly differ between groups (Kruskall-Wallis, p=0.92). More WHDs occured in the rivaroxaban group (5/20), compared to enoxaparin (2/20) and dabigatran (3/20). Conclusions. None of the chemical TR is superior to others in terms of reducing the BL. There seems to be more WHDs with the use of oral agents - this finding needs further studies. Level of evidence. 1b (Centre for Evidence Based Medicine, Oxford). Approval. This study was approved by The Medical Centre of Postgraduate Education Ethical Committee. Disclosure. The authors disclose no competing interests

Background. There are multiple documented advantages of undertaking total knee arthroplasty (TKA) without tourniquet, however, increased rates of blood loss and transfusion are often cited as contraindications to this approach. The aim of this study was to examine the effect of intra-operative TA administration on blood loss and transfusion rates in TKA without pneumatic tourniquet, using Rivaroxaban as thrombo-embolic prophylaxis. Method. 120 patients split into two continuous data sets, (A+B), underwent TKA without application of above knee tourniquet, receiving a post operative dose of oral Rivaroxaban within 8 hours. Group B patients received an intra-operative dose of 1 gram of Tranexamic Acid intravenously before the first cut, whilst those in group A did not. Haemoglobin and haematocrit levels were recorded peri-operatively. A revised Gross formula was used to calculate blood loss. Four patients were excluded from the study for incomplete data. Results. 58 patients (M34F24) in Group A, average age 6, had a mean haemoglobin drop of 33gram/litre, haematocrit drop of 0.097litre/litre (9.7%), with an average calculated blood loss of 1393ml. 58 (M34, F24) patients in group B, average age 67, had a haemoglobin drop of 25.2gram/litre, haemotocrit drop of 0.076litre/litre (7.6%) with an average calculated blood loss of1079ml. Thus Group A patients were seen to sustain significantly more blood loss without TA administration, with a 29.1% larger calculated blood loss, a 25.5% larger drop in haemoglobin and a 27.6% larger fall in haematocrit. Transfusion rate was 5.2% (3 patients) per group. Conclusion. TA was shown to be effective in reducing blood loss in TKA without tourniquet using Rivaroxaban. Transfusion rates of 5.2% across both groups is close to 1/10th of the transfusion rate reported for some major studies of TKA using Rivaroxaban with tourniquet application, and 1/8th of the transfusion rate in studies of TKA with administration of TA and use of tourniquet. Level of Evidence. Level-III. The authors report there are no relevant disclosures to make. Ethical approval was granted for the study

Rivaroxaban has been recommended for routine use as a thromboprophylactic agent in patients undergoing lower-limb arthroplasty. Starting January 2011, our unit has converted from aspirin to Rivaroxaban use routinely following lower-limb arthroplasty for venous thromboembolism (VTE) prophylaxis. The aim of this audit was to retrospectively review its efficacy and the morbidity associated with its use. All patients undergoing primary and revision lower-limb arthroplasty between February 2011 and July 2011 were reviewed. All patients undergoing total knee replacement surgery and total hip replacement surgery received oral rivaroxaban 10 mg daily post-operatively for 14 days and 35 days respectively. Outcome measures recorded were; investigation for DVT/PE, rate of DVT/PE, wound complications (infection, dehiscence, leaking, bleeding), blood transfusion rate and readmission rate within 6 weeks of surgery. Of the 162 patients identified, 19 were excluded due to insufficient information or because they did not receive rivaroxaban as VTE prophylaxis. 141 patients (mean age 71.7 years) were included. 69 primary and 5 revision total knee replacements were performed. 60 primary and 7 revision total hip replacements were performed. 9 patients (6.4%) underwent Doppler USS for a painful swollen leg with 1 (0.7%) DVT diagnosed. None were investigated for a pulmonary embolus. 25 (17.7%) patients developed wound complications: 10 superficial infections requiring oral antibiotics, 2 deep infections requiring theatre washout, 1 wound dehiscence, 5 continuously leaking wounds, 5 bleeding wounds/haematomas. 26 (18.4%) patients required post-operative blood transfusion (average 2.2 units). 12 (8.5%) patients were re-admitted within 6 weeks with post-op complications (6 wound complications, 5 painful/swollen limbs, 1 large per-vaginal bleed). In keeping with previous literature, the rate of VTE following lower-limb arthroplasty using rivaroxaban as prophylaxis is low. However, the rate of morbidity was higher when compared with the use of aspirin in our centre between April and September 2010

Background. The incidence of bleeding following primary TKR has increased with the use of chemical thromboprophylaxis. Our aim was to compare Clexane, Apixaban and Rivaroxaban in terms of frequency and volume of bleeding episodes, need for blood transfusion, return to theatre and incidence of VTE events. Methods. Between February and May 2014, a consecutive series of 132 primary TKRs were studied prospectively. The wound dressings of these patients were assessed daily to look for signs of bleeding and classified into: Mild (< 50p size coin), moderate (> 50p size coin) or Severe (blood seeping through the dressing). Follow up was up to minimum of 30 days post discharge. Results. Apixaban, Rivaroxaban & Clexane were used in 64, 23 and 45 patients respectively. Eleven patients had at least 1 day of mild bleeding, 8 had at least 1 day of moderate bleeding and 11 had at least 1 day of severe bleeding. Ten patients had 1 or more doses omitted because of bleeding. However, there was no statistical significance in distribution of bleeding episodes or doses omitted due to bleeding amongst the three drugs (chi squared test). There was also no correlation between number of severe bleeding episodes and the need for blood transfusion. There were two VTE events recorded; 1 PE each in the Apixaban and Rivaroxaban groups. Two cases in the Apixaban group and 1 case in the Clexane group returned to theatre for washout of haematoma. Conclusion. There was an 8% incidence of severe bleeding in our study group. The incidence of bleeding problems following TKR was similar in the Apixaban, Rivaroxaban & Clexane groups. Level of evidence. III - Evidence from case, correlation, and comparative studies

Since the establishment of our department a multi-modal approach to thromboprophylaxis that uses aspirin for chemical prophylaxis was adopted. In accordance with the latest national recommendations, our routine chemical prophylaxis following arthroplasty was changed to rivaroxaban in 2012 and then dalteparin in 2013. This study aimed to compare venous thromboembolism (VTE) rates during the use of the aspirin-based protocol used from 2004 to 2011 with recent, rivaroxaban and dalteparin-based guidelines. Outcome data from ISD Scotland was retrieved and radiology reports performed for CT pulmonary angiograms and lower limb doppler ultrasound scans in our institution were assessed to identify cases of VTE following primary hip or knee arthroplasty. The incidence of pulmonary embolism (PE) and proximal deep venous thrombosis (DVT) was calculated for each year and compared using a Chi-squared test. Additionally, the change in extended thromboprophylaxis regimen was surveyed by recording the discharge prescriptions for consecutive arthroplasty patients for March every year. There were 90 radiologically confirmed cases of DVT or PE between 2004 and 2011 (incidence of 0.71%). The DVT/PE rate was subsequently 0.67% in 2012 and 0.69% in 2013, with a further 29 cases identified. This does not represent a significant change in the venous thromboembolism rates and remains below the national incidence of VTE (1.06%). Aspirin alone was used as chemical thromboprophylaxis in 80.8% of patients from 2004 to 2011, 50.9% in 2012, and 12.1% in 2013. The incidence of VTE at our centre remains favourable to national figures, but the modification of thromboprophylaxis guidelines will incur additional financial costs and has not had a significant reduction on the rate of VTE

Objectives

We have increased the dose of tranexamic acid (TXA) in our enhanced total joint recovery protocol at our institution from 15 mg/kg to 30 mg/kg (maximum 2.5 g) as a single, intravenous (IV) dose. We report the clinical effect of this dosage change.