Blood management protocols attempt to reduce blood loss by strategies including autologous blood donation, red cell salvage, normovolaemic haemodilution and haemostatic agents such as tranexamic acid (TXA). TXA usage in particular has become increasingly commonplace with numerous studies demonstrating a significant reduction in peri-operative blood loss and proportion of patients requiring transfusion, without increasing the risk of venous thromboembolism. Tourniquet usage has now become ubiquitous in TKA operations with reported benefits of improved visualization, shorter operative time and decreased intra-operative bleeding. However, its use is not without considerable complications including wounding dehiscence, increased venous thromboembolism, superficial wound infection and skin blistering. It is therefore imperative that we review tourniquet usage in light of ever evolving blood management strategies. The aim of this study was to evaluate the effect of stopping tourniquet usage in primary TKRs, performed by an experienced surgeon, in light of new blood reduction measures, such as a TXA. A retrospective analysis identified a total of 31 patients who underwent primary TKR without the use of a tourniquet from January 2018 to March 2019. This was compared to an earlier group of patients from the same surgeon undergoing TKR with the use of a tourniquet; dating from July 2016 to November 2017. All surgeries were performed within the same hospital (CXH). Peri-operative factors and outcome measures were collected for analysis. There was no significant difference in post-operative haemoglobin drop (Tourniquet, 23.1 g/L; No Tourniquet, 24.4 g/: p=0.604) and fall in haematocrit (Tourniquet, 0.082; No Tourniquet, 0.087: p=0.604). Allogenic blood transfusion rates were the same in both groups at 12.9% (2 patients) and blood loss was not found to be significantly different (Tourniquet, 1067ml; No tourniquet, 1058mls). No significant difference was found in operative time (Tourniquet, 103 minutes; No Tourniquet, 111.7 minutes: p=0.152) or length of stay (Tourniquet, 5.5 days; No Tourniquet, 5.2 days: p=0.516). Tranexamic acid usage was not found to be significant (p=1.000). ROM of motion and analgesia requirement was significantly better in the no tourniquet group on one post-operative day out of five analysed (p=0.025, p=00.011). No post-operative thromboembolic events were reported in either group. There was no significant difference in readmission rates (p=0.492) or complications (p=0.238). The increase in minor complications and potential increased VTE risk with tourniquet usage must be balanced against an improved visual field and reduced blood loss in TKR patients. Our study found no difference in post-operative blood loss and transfusion rates between tourniquet and no tourniquet groups. With ever evolving and improving blood loss management strategies, including the use of TXA, the application of tourniquet may not be needed. Further prospective RCTs are needed to assess the impact of tourniquet usage in light of this

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

Introduction and Objective. Total joint replacement is indicated for osteoarthritis where conservative treatment has failed, and in the UK the number of patients requiring hip and knee replacements is set to increase with an ageing population. Survival of total hip replacements is around 85% at 20 years with the most common reason for revision being aseptic loosening of the implant secondary to osteolysis, which is caused by immune-mediated reactions to implant debris. These debris can also cause pseudotumour formation. As revision surgery is associated with higher morbidity, mortality, infection rates, venous thromboembolism, resource demand and poorer subsequent function it is important to understand the mechanisms underlying the pro-inflammatory process to improve implant survival. Toll-like receptor 4 (TLR4), an innate immune receptor, has been demonstrated to mediate deleterious immune responses by the Tyson-Capper research group, including inflammatory cytokine interleukin-8 (IL-8) secretion. Statin use in epidemiological studies has been associated with reduced overall risk of revision surgery after hip replacement. In-vitro studies have demonstrated the potential for statins to reduce orthopaedic debris-induced immune responses which can lead to osteolysis and pseudotumour formation. As literature from cardiological investigations demonstrate that statins can reduce the expression and responsiveness of TLR4, this could be an exciting mechanism to exploit to reduce the host immune response to orthopaedic wear debris, thereby improving implant survival by reducing immune mediated osteolysis. This ongoing study investigates simvastatin's effect on cobalt ion-mediated changes in gene and protein expression of interleukin-8 and soluble-ICAM-1 (sICAM-1) which is an angiogenic factor implicated in pseudotumour formation. Materials and Methods. TLR4-expressing human monocyte/macrophage THP-1 cells were pre-incubated with 50μM simvastatin for 2-hours or a vehicle control, before being exposed to exposed to 0.75mM cobalt chloride, in addition to a further 24-hour co-incubation with 50μM simvastatin or vehicle control. IL-8 protein and sICAM-1 secretion was measured by enzyme-linked immunosorbent assay (ELISA). Gene expression changes were quantified by TaqMan-based real time polymerase chain reaction. Results. Pre-treatment with simvastatin significantly reduced cobalt-mediated IL-8 protein secretion (n=3) and sICAM-1 protein secretion (n=2) in THP-1 cells (p-value<0.0001). Work will be undertaken to determine changes in gene expression, the role of TLR4 in these responses and the effect of simvastatin on additional inflammatory markers. Conclusions. Simvastatin significantly reduces cobalt-ion mediated IL-8 and sICAM-1 protein secretion in THP-1 cells. This in-vitro finding demonstrates the potential for simvastatin to reduce recruitment of leukocytes which mediate the deleterious inflammatory processes driving aseptic loosening and pseudotumour formation

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

Background. Total Knee Replacement (TKR) is one of the most common surgeries in our speciality, with a high risk of significant blood loss and consequent transfusion. The drain clamping is usually applied to reduce both blood loss and transfusion in this procedure. However, this method is still somewhat controversial too. Method. We performed a prospective randomised study of 74 patients with advanced knee osteoarthritis. All were treated in our centre with TKR. The patients were randomly assigned into two groups. In group A we included patients whose drainage system was clamped temporarily (during the first 6 postoperative hours). Group B includes those patients in who we use traditional system, with continuous suction drain that was placed after surgery. Results. A statistically significant difference in haemoglobin loss after surgery was found, with 0.83 g/dl less decline in patients with temporary clamping drains. The decrease of haematocrit levels, the blood loss or the number of transfusions were lower in the temporary clamping group, but without statistic significance. No cases with wound infection neither clinical venous thromboembolism were detected in our group. Conclusions. These results suggest that drainage clamping during the first 6 postoperatative hours reduces the postoperative anaemia, without increasing morbidity after TKR

Background. Traditionally, a Surgical Tourniquet (ST) is used during Total Knee Replacement Surgery (TKRS) to prevent blood flow to the leg and improve the surgical field of view. The use of a ST is known to increase the risk of venous thromboembolism. Echogenic material, suggestive of emboli has been observed in the brain following ST deflation in TKRS despite the absence of a patent foramen ovale, likely through pulmonary shunts. The aim of this study was to assess whether cerebral emboli result from tourniquet use in TKRS and the sequelae of any emboli. Methods. 11 subjects from a single centre undergoing routine TKRS with a ST gave informed consent. Each participant had diffusion weighted MR brain imaging prior to, and within 48 hours after TKRS and completed pre and post-operative mini-mental state examinations (MMSE). Results. Pre and post-operative MR imaging were assessed by a senior radiologist and the results were reported according to Age and Cognitive Performance Research Centre (ACPRC) rating scale. There were no changes from pre and post-operative MR scans. 4 participants (36%) had no change in MMSE scores. These participants had a score of 1 or 0 in both MR scans. 7 participants (63%) had a score of 2 or 3. These participants had mean 2.8 point (9.5%) drop on MMSE (IQR = 1) within 48 hours. Conclusions. In this small, exploratory study we found no evidence of discrete cerebral emboli occurring with the use of ST in TKRS. Interestingly, participants noted to have minimal or no pre-operative ischaemic change appeared to maintain more cognitive function post-operatively than those with higher levels of pre-existing ischaemia. Subtle changes in ischaemic load in patients with pre-existing ischaemia may lead to impaired cognitive function, however further evidence is required to confirm this theory. Level of Evidence. III. Approval. Protocol approved by NRES Committee Yorkshire & The Humber, Leeds West and The Research, Development & Innovation Department University Hospitals Coventry & Warwickshire

Introduction. Guidelines from the North American Spine Society (2009 and 2013) are the best evidence-based instructions on venous thromboembolism (VTE) and antibiotic prophylaxis in spinal surgery. NICE guidelines exist for VTE prophylaxis but do not specifically address spinal surgery. In addition, the ruling of the UK Supreme Court in 2015 resulted in new guidance on consent being published by the Royal College of Surgeons of England (RCSEng). This study assesses our compliance in antibiotic, VTE prophylaxis and consent in spinal surgery against both US and UK standards. Methods. Retrospective review of spinal operations performed between August and December 2016. Case notes, consent forms and operation notes were analysed for consent, peri-operative antibiotic prescribing and post-operative VTE instructions. Results. Four Spinal surgeons performed 45 operations during this period. 31 patients (69%) received a copy of the signed consent with this process being formally documented in 22 (71%) of those cases. All patients were consented by a competent surgeon. 82% of cases consented prior to the date of procedure were countersigned on the day of operation. There was a mean time of 25.3 days between initial consent and operation (Range: 0–170). 37 (82%) cases had clear instructions for VTE and antibiotic prophylaxis. All prescribed post-operative antibiotics were administered. Discussion. The North American Guidelines state that prophylactic antibiotic is appropriate in all spinal surgery with prolonged cases requiring intraoperative re-dosing and only complex cases needing a postoperative regimen. Eight patients underwent a complex procedure and 7 appropriately received postoperative antibiotics. Of the 29 patients that underwent a simple procedure, 12 did not receive post-operative regimen, in line with the guidelines. However, the remainder 17 were over treated. The US Guidelines recommend mechanical VTE prophylaxis only in elective spinal surgery except in high risk patients. All our patients received VTE mechanical prophylaxis. RCSEng guidelines require consent being taken prior to procedure by a competent surgeon and confirmed on day of procedure. All patients in our cohort were consented prior to the date of operation allowing time for considering options and independent research. 82% of patients had consent confirmed on day of operation. Conclusion. This study demonstrates that we met guideline advice for all patients with regards VTE prophylaxis. We have a tendency to over treat with post-operative antibiotics and not all patients had their consent confirmed on day of procedure but was consented well before day of operation. North America still lead the way with guidelines on spinal surgery to which we should adhere, with NICE guidelines providing limited instructions. New consenting guidelines from RCSEng may not be currently widely known and thus should be a source of education for all surgeons

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

Due to working time restrictions a full-shift cross-covering system is commonplace. As more than one surgeon is responsible for trauma admissions in a 24-hour period a complete handover is paramount to ensure continuity of care. The purpose of this audit was to determine whether the introduction of a formal handover/admission form would improve this continuity with regards to prescription of venous thromboembolism (VTE) prophylaxis in hip fracture patients. In Stirling Royal Infirmary chemical VTE prophylaxis for hip fracture patients is 40mg enoxaparin at 6pm unless there is a contraindication. Over a 14-day period we prospectively documented the prescription of VTE prophylaxis and doses missed under the current admissions system. Following this a proforma was introduced that was to be exchanged at handover meetings. The proforma included patients' name/details, admission ward, and tasks to be completed during clerk-in, including VTE prophylaxis prescription. Tasks outstanding at handover had to be documented and completed by the subsequent doctor. Each form was signed and dated by the receiving doctor. We subsequently re-evaluated the prescription of VTE prophylaxis in hip fracture patients. Between 1/12/10-15/12/10, 23 patients were admitted with hip fracture. 12 had appropriate VTE prophylaxis, 6 missed one dose, 4 missed two, and 1 missed three all due to failure of prescription. Following the introduction of the proforma, 12 patients were admitted with hip fractures between 31/12/10-14/1/11. All were prescribed appropriate VTE prophylaxis and missed no doses. 1 patient was on warfarin and had enoxaparin prescribed but withheld until INR< 2.0. After the introduction of a handover form VTE prophylaxis prescription vastly improved. This proforma ensured that all elements of initial management were completed allowing for physician accountability, greater efficacy of handover and continuity of care

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

The reinfusion of perioperative cell salvage is one method employed to reduce exposure to donor blood. Data on the safety of this process, however, are scant. Notably, the effect of intraoperative, washed cell salvage reinfusion on prothrombotic markers has not been demonstrated. The risk of postoperative venous thromboembolism following major orthopaedic operations is not insignificant. The study objective was to assess the effect of cell salvage reinfusion on coagulation and platelet activation. Twenty-one patients undergoing elective primary hip operations were recruited. Nine patients received washed cell salvage intraoperatively, and were compared with 12 patients undergoing similar surgery that did not. Two patients in the cell salvage group also received postoperative, unwashed cell salvage. Blood samples were collected pre-operatively, immediately post-operatively, and one day post-operatively for assays of platelet activation markers, P-selectin expression and fibrinogen binding by flow cytometry in diluted whole blood; coagulation activation marker, thrombin-antithrombin complex (TAT); D-dimer by ELISA, thrombin generation by chromogenic assay, and full blood count. Samples of cell salvage material were also analysed for prothrombotic markers. There were no significant differences between the groups preoperatively. Postoperatively haemoglobin levels did not differ significantly between the cell salvage group and controls. Postoperative TAT and D-dimer were significantly higher in the cell salvage group compared with controls (p<0.05). One day postoperatively, there were significantly higher platelet P-selectin expression (p=0.006) and platelet fibrinogen binding (p=0.004) in the cell salvage group compared with controls. The white cell count (WCC) was also significantly higher (p=0.04). In the intraoperative washed cell salvage material, and in postoperative cell salvage, the platelet count was low, but significant proportions of platelets were activated, and levels of D-dimer were elevated compared with venous blood. The postoperative salvage material also contained high levels of TAT. The results from this pilot study show the induction of a prothrombotic state following reinfusion of intraoperative, washed cell salvage in recipients undergoing primary elective hip operations. An inflammatory response to reinfusion is also indicated by the raised WCC. Further investigation into the safety of cell salvage is indicated

INTRODUCTION. Warfarin remains the treatment of choice for the majority of patients with venous thromboembolism, atrial fibrillation and valvular heart disease or valve replacement unless contraindicated. Poor management of patients on warfarin often leads to delay in surgery, life threatening bleeding during or after operation and unnecessary delay in discharge from hospitals in United Kingdom. METHODS. We carried out a prospective study on patients who were on warfarin and underwent elective and emergency orthopaedic procedures during period of study- August 2007 to April 2008. All patients included in the study were identified from admission notes during period of study. All data regarding indications for warfarin, pre and post procedures INR, elective or emergency orthopaedic procedures and complications were collected using a standard proforma. RESULTS. 18 patients, 12 male and 6 female were included into the study. Patients' age ranged from 47-87 with mean of 76. The indications for warfarin therapy were atrial fibrillation in 12 patients, deep vein thrombosis in 5 patients and left ventricular aneurysm in 1 patient. 18 procedures, 10 elective and 8 emergency orthopaedic procedures were carried out during period of study. Elective procedures - 7 primary joint arthroplasty, 1 revision hip arthroplasty, 1 removal of metalwork and 1 metatarsophalangeal joint fusion. Emergency procedures - 4 hip hemiarthroplasty, 2 dynamic hip screw fixation, 1 external fixator application and 1 open reduction and internal fixation of ankle. All elective admission patients were pre-assessed in clinic prior to admission and were advised to stop warfarin based on their INR level. Patients with INR 2-3 had their warfarin stopped 4 days prior to surgery while patients with INR 3-4.5 had their warfarin stopped 5 days prior to surgery. This group of patients had their INR check on admission and ranged from 1.1-1.5. This group of patients had no reversal therapy and no cancellations were made to their operation. 8 emergency admission patients had INR of 1.4-4.7 on admission with mean of 2.7. 5 patients had reversal therapy while 3 patients had no reversal therapy. Pharmacological methods used to reduce the INR were fresh frozen plasma in 1 patient and Vitamin K in 4 other patients. 2 patients that received reversal therapy had operation on day 1, 2 on day 3 and 1 on day 5. 1 patient that had no reversal therapy was operated on day 1, 1 on day 3 and 1 on day 5. Patient that received no reversal therapy and operated on day 5 of admission died post-operatively from medical complications. Mean delay for patient that had reversal therapy was 2.2 days compared to 3 days in patient with no reversal therapy. All patients in this study had prophylactic low molecular weight heparin while off warfarin. Patients were recommenced on their normal dose of warfarin the day after their operation. DISCUSSION & CONCLUSIONS. We conclude that patients on warfarin with INR 2-3 should have their warfarin stopped 4 days prior to surgery while patients with INR 3-4.5 should stop their warfarin 5 days prior to elective surgery. Trauma patients on warfarin requiring operation should have their INR reversed on admission to shorten delay in waiting time and improve outcomes

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.