Aim. To evaluate safety and efficacy of performing a total knee arthroplasty (TKA) on patients receiving continuous Warfarin therapy. Methods. We identified 24 consecutive patients receiving long term warfarin therapy who underwent total knee arthroplasty between 2006 and 2008. As a control, we collected the same data from a group of age and sex matched patients not on warfarin. Primary observations were changes in haemoglobin, transfusion rates and complications. Secondary observations were fluctuations in the INR and post operative range of motion (ROM). All procedures were performed by the senior author in a single centre using the same TKA technique. Results. There was no significant difference between the warfarinised and non warfarinised groups in preoperative or postoperative haemoglobin. After unilateral TKA 38% of non warfarinised patients and 24% of warfarinised patients required a blood transfusion. Both the warfarin and non warfarin groups had a bilateral TKA transfusion rate of 67%. In the warfarin group the mean preoperative INR was 2.2 (SD=0.46; range 1.0 to 3.0) and mean postoperative INR was 2.6 (SD=0.8; range 1.5 to 5.0). There were no surgical delays due to a high INR level. The mean change in INR during the perioperative phase was minimal (mean 0.4; SD=0.7). In the warfarin group the mean flexion range of motion was 116° preoperatively, 88° at 5 days, 107° at 6 weeks and 117° at 12 months after surgery. There was no significant ROM difference between the warfarin and non warfarin groups. There were no post operative bleeding complications. Conclusions. Current American College of Chest Physicians (ACCP) guidelines recommend bridging therapy for high risk patients receiving oral anticoagulation undergoing major orthopaedic procedures. We have shown that a safe alternative is to continue the steady state warfarin perioperatively in patients on long term warfarin therapy requiring TKA

Hip fractures are a common cause of morbidity and mortality in the elderly, with approximately 30,000 hip fractures a year in Canada. Many hip fracture patients are prone to heart failure and present anticoagulated with Warfarin for medical comorbidities including atrial fibrillation or previous thromboembolic disease. Reversal of warfarin anticoagulation to an INR < 1.5 preferred for surgery but this often contributes to a delay to hip fracture surgery, which increases patient pain, morbidity, mortality, and length of stay Octaplex is a small-volume prothrombin complex concentrate (PCC) that reverses Warfarin-related anticoagulation in 15–60 minutes. It has been shown to be safe and effective in the management of intracranial and gastrointestinal bleeding in warfarinised patients. It is recommended by Bone and Joint Canada as an option for urgent warfarin reversal in hip fracture patients. However, there has been no published literature on the use of Octaplex or other PCCs in orthopaedic patients. Our objective is to assess the effectiveness of Octaplex for rapid reversal of warfarin anticoagulation in hip fracture patients. A database review of all patients who received Octaplex was performed. Medical records of all hip fracture patients in Calgary who received Octaplex between December 2009 and February 2015 were reviewed. After application of inclusion and exclusion criteria, 33 patients were identified. A timeline of International Normalised Ratio (INR), Octaplex administration, and hip fracture surgery was recorded. Mortality and complications were assessed at 30 days. A single dose of Octaplex corrected the INR to < 1.5 in 29 cases (88%). Median time from administration of Octaplex to a measured INR < 1.5 was 1.1 hours. Median time from admission to hip fracture surgery was 22 hours. Mortality at 30 days was 15.2%, mostly from cardiac arrest. A further 12% of patients developed cardiac or thrombotic complications. Multiple medical comorbidities were common including coronary artery disease (55%), congestive heart failure (45%), and chronic pulmonary disease (39%). Patients who received both fresh frozen plasma (FFP) and Octaplex for warfarin reversal had much higher mortality than those who only received Octaplex (40% vs 4.3% mortality at 30 days), but also had more medical comorbidities. Octaplex is effective at rapidly reversing warfarin anticoagulation and reducing time to surgery, potentially reducing the morbidity and mortality of hip fractures. Administration of both Octaplex and FFP were associated with higher early mortality in this case series. Further research is required to assess the safety of Octaplex, vitamin K, and FFP for reversal of warfarin anticoagulation in this population

Various studies have demonstrated that the necessity for reversal of Warfarin through the use of Vitamin K (Vit K) in neck of femur fracture patients introduces increased duration of stay and poorer outcomes as measured by operative complications and mortality rate. One reason for this delay may be the time latency between admission and the clinicians decision to investigate the INR. In this study we aim to explore the different causes of latency which contribute to a delay to theatre and ascertain whether point of care testing may negate this. We carried out an audit of a cohort of neck of femur fracture patients between 2012 and 2015. Between September 2011 and September 2013, paper notes of 25 patients who were on warfarin at the time of sustaining a Neck of femur fracture (NOF) was obtained within Addenbrookes hospital archives. An additional 80 patients records from the year 2015 were retrieved from EPIC digital records. Time intervals were recorded as follows (from time of A&E assessment by Medical doctor); Interval to orthopaedic specialist assessment, Interval to first INR order, Interval to first INR result seen by specialist, Interval to first Vit K prescribed, Interval to first Vit K given, Interval to Second INR ordered, Interval to second INR seen by specialist, Interval to operation time (as determined by time of team briefing). Analysis of the time intervals as a proportion of total time elapsed between A&E assessment and Time to theatre was performed. Point of care (POC) testing of INR on admission to A&E was introduced and a symmetrical time period was analysed for the same intervals. The latency generated by time taken for a NOF to be assessed by an orthopaedic specialist occupied 8.60% of the total time, the interval between ordering and recording an INR value accounted for 7.96% of time to theatre, the interval between an INR being recorded and subsequently seen by a clinician accounted for 13.4% of time to theatre, the time between orthopaedic specialist assessment and prescription of Vit K took up 7.83% of the total time and the percentage time between Vit K prescription and administration was 12.3%. The time between the first dose of Vit K prescription and arriving at theatre accounted for 76.1% of latency and the time between viewing a second INR and time to theatre occupied 33% of the total time. Following introduction of POC INR testing, there was a statistically significant decrease in time taken for warfarin reversal and consequently a reduction between time of admission to time to theatres. NOF patients who are on warfarin at time of injury introduces complexity to surgical management and planning for theatre. In our audit we demonstrate that causes of delay are distributed throughout the pathway of care and there are several stages. POC INR testing represents an effective method of reducing this latency and improves patient outcome

Patients with hip fractures should have surgery within 36 hours of admission to hospital. This reduces mortality and is required for hospitals to receive the NHS Best Practice Tariff. Many patients with hip fractures take Warfarin and reversing the effect of this frequently delays surgery. We report the results of a case-control study. The primary outcome measure was the number of patients with an INR of 1.7 or less on the day following admission to hospital. This is considered an acceptable INR for hip fracture surgery in our department. In the control group the dose of Vitamin K given was decided by the admitting doctor based on the patients' INR. In the intervention group all patients received 5mg of IV Vitamin K on admission. They had their INR rechecked at 6:00am the following morning and a further 2.5mg of Vitamin K was given if it was 1.8 to 2.0 and a further 5mg of Vitamin K was given if it was greater than 2.0. 350 patients with hip fractures were admitted to our department and 26 (7.4%) of these were taking Warfarin. The control group contained fourteen patients who had a mean INR of 3.3 on admission. The time taken to achieve an INR of 1.7 or less was one day for four patients; two days for nine patients and three days for one patient. The intervention group contained twelve patients who had a mean INR of 2.7 on admission. The time taken to achieve an INR of 1.7 or less was one day for eleven patients and two days for one patient. There were no complications caused by Warfarin reversal. A high proportion of patients with hip fractures take Warfarin. This can be reversed promptly and safely using our protocol

Introduction. There is insufficient data on the trends of anticoagulation after total knee arthroplasty (TKA) in the USA, and the efficacy and safety of rivaroxaban, beyond randomized clinical trials and small cohort studies. Patients and Methods. Using the Truven Health MarketScan database, we retrospectively evaluated new anticoagulation prescriptions after elective TKA from 2010 to 2015. The frequency of deep vein thrombosis (DVT), pulmonary embolism (PE), and adverse events, within 90 days, were then evaluated in 24,856 new users of warfarin and 21,398 new users of rivaroxaban in commercially insured patients (COM), and 15,483 new users of warfarin and 8,997 new users of rivaroxaban in Medicare supplement patients (MED). Data was analyzed by odds ratios using logistic regression models with stabilized inverse probability treatment weighting. Results. Warfarin use decreased from approximately 50% to 17% in COM patients and 60% to 25% in MED patients. Rivaroxaban use increased from 0 to 35% in COM patients and from 0 to 39% in MED patients. Older patients, females, a history of DVT, renal impairment, use of antiplatelet agents or surgery performed as an outpatient had lower odds of getting rivaroxaban. Patients in Western region and having surgery in 2015 had higher odds of getting rivaroxaban. COM patients with capitated insurance plans and a history of PE had lower odds of rivaroxaban initiation. MED patients with atrial fibrillation, cardiovascular disease or hyperlipidemia had lower odds of rivaroxaban initiation. Warfarin users had significantly higher odds ratio of DVT (OR 2.06 in COM patients and OR 2.21 in MED patients) and PE (OR 2.03 in COM patients and OR 2.16 in MED patients) than rivaroxaban users. There were no statistically significant differences in the bleeding risk between the two agents, but warfarin users had a significantly higher odds ratio of periprosthetic infection in both COM (1.57) and MED (1.79) patients. Conclusions. There has been an increase in prophylaxis with rivaroxaban, and a decrease in both warfarin and LMWH use after elective TKA over four years. Rivaroxaban had lower odds ratio of both DVT and PE than warfarin, and bleeding risks were similar. For figures, tables, or references, please contact authors directly

Aim: To evaluate the effect of Warfarin, the prevalence of acceptable level of INR by the anaesthetist, leading to delay of surgery in patients with fracture neck of femur and the outcome of such treatment. Material and Methods: We retrospectively reviewed all patients admitted with fracture neck of femur who were on Warfarin in the year 2002. In total 9 out of 135 pt were on Warfarin. Their entire medical records were scrutinised. A control group of similar age, sex and pre- morbid conditions was identified. A telephone survey was then conducted. In warfarin group average delay in surgery was 4 days (1 to 7) , needed 76% more blood test, total morphine 40mg and Codeine 960mg, 60% longer stay and after all 78% had General anaesthesia. The six hospital survey showed the estimated number of such patients averaged 2 (1 to 4) per year, delay in surgery of 2 to 5 days and acceptable INR between 1.5 to under 3. Conclusion: We found that we under estimate the number of patients on Warfarin. These patient had a significant delay in surgery requiring more analgesic both oral and parental, no significant post- op complications but a much longer hospital stay causing significant increase in morbidity, bed block and expenditure. We were surprised that there is no consistently acceptable level of INR to perform the surgery and type of anaesthesia

Background. The optimal strategy for postoperative deep venous thrombosis (DVT) prophylaxis remains among the most controversial topics in hip and knee arthroplasty. Warfarin, the most commonly used chemical anticoagulant, initially causes transient hypercoagulability; however the optimal timing of treatment with respect to surgery remains unclear. Our purpose was to evaluate the effects of pre- versus postoperative initiation of warfarin therapy with a primary endpoint of perioperative change in hemoglobin (pre- minus post-operative level), with secondary endpoints of postoperative International Normalized Ratio (INR), drain output, and bleeding/thrombotic events. Methods. A quasi-experimental study design was employed, under which patients were assigned to begin taking warfarin the night prior to surgery or the night following surgery based on day of the week seen in clinic. An a priori power analysis was conducted in order to ensure appropriate enrollment to detect a 0.5 g/dL difference in perioperative change in hemoglobin between groups, given an alpha level of 0.05 and beta of 0.80. Based on the results, the study included all primary, elective total hip and knee arthroplasties performed by a single surgeon over a 12 month period. Fifteen patients were excluded (7 chronic anticoagulation, 3 hip fractures, 2 medical contraindications, 3 simultaneous procedures), leaving 165 cases (108 hips, 57 knees) available for study. Of these, 73 received warfarin preoperatively (49 hips, 24 knees) and 92 postoperatively (59 hips, 33 knees). Warfarin was dosed according to a standard nomogram in both groups. INR (on postoperative days 1 and 2), perioperative decrease in hemoglobin (difference between level preoperatively and on postoperative days 1 and 2), and drain outputs were compared between groups using a student t test. Adverse events (transfusions, hematomas, epidural complications, and pulmonary embolus) were compared using two-tailed Fischer's exact test. Results. No statistically significant difference in perioperative hemoglobin change was observed between treatment groups on either postoperative day 1 (mean 3.279 versus 3.377, p=0.6824) or 2 (mean 4.0 versus 4.12, p=0.6831). As expected, the preoperative warfarin group demonstrated higher INRs on both postoperative days 1 (mean 1.18 versus 1.12, p=0.0023) and 2 (mean 1.46 versus 1.31, p=0.0006). Of note, preoperative warfarin dosing was also associated with significantly lower drain outputs (mean 185.4 versus 268.7, p=0.0025). 9 transfusions (4 preoperative dosing, 5 postoperative dosing), 3 hematomas (1 preoperative dosing, 2 postoperative dosing), and 1 pulmonary embolus (preoperative dosing) occurred, but no significant difference could be detected given the numbers available for study. Conclusions. Initiation of warfarin pre- rather than postoperatively was not associated with a significant difference in perioperative hemoglobin change, although a significant reduction in drain output was observed. Larger studies are needed to determine whether the risk of adverse events is increased with either dosing strategy

Introduction. There are no specific and clear guidelines regarding management of trauma patients who are on Warfarin. The objective of this study was to compare two methods of anticoagulation management in the pre-operative period for this group. Methods. This study was conducted in two phases. In the first half (October 2005 to April 2006) the trauma patients on Warfarin were managed by the traditional method. The second group of patients who were admitted during May to December 2006 was given a single stat dose of Vitamin K (1 mg IV) in addition to stopping Warfarin and starting low molecular weight Heparin. There were 90 patients in this study, 45 in each group. There was no statistically significant difference in age distribution, INR on admission and medical co-morbidities in the two groups. Majority of patients were admitted with fracture neck of femur (43 in each group). All the patients had INR more than 1.5 on admission. Results. INR levels decreased to 1.5 or less in 3.8 days in the first group and 1.6 days in the second group (p< 0.05). The delay in surgery was 6.6 days in group one and was 2.8 days in the patients in group two (p< 0.05). Four patients in the group who did not receive Vitamin K developed medical complications in the pre-operative period. Patients given one dose of Vitamin K did not have any complications pre-operatively. There was no adverse effect of Vitamin K therapy like haemorrhage or clinically evident thrombosis. Conclusion. In our experience 1 mg of intravenous Vitamin K on admission for Warfarin reversal in patients requiring operative management of femur fractures is a safe and effective treatment to avoid delay in treatment

Introduction. Management of a patient with a neck of femur (NOF) fracture is a key aspect of orthopaedic trauma care, with around 75 000 new cases in the United Kingdom annually costing the health care over £ 2 billion. Delaying time to theatre for operative intervention of hip fractures negatively impacts on patient outcome and is one of the key aspects of the hip fracture best practice tariff (BPT). One aspect of the peri-operative management of patients with hip fractures implicated in delayed surgery is the use of long term warfarin for anticoagulation. Anticoagulation reversal is a common cause of operative delay. Aim. The aim was to establish the impact this cohort of population had on achieving the BPT and how we could improve it. Material and Methods. Retrospective data was collected over a period of 12 months using the national hip fracture data base (NHFD). The delay to theatre specifically those who were on warfarin was identified. 10 % of the identified cohort was delayed to theatre due to high international normalised ratio (>1.5) and failed to achieve BPT. This cost the trust a loss of around £ 43,200. We have now introduced a simple hand-held warfarin testing device in accident and emergency. All patients on warfarin from history will have a pin prick and instantaneous INR estimated while the routine bloods are dispatched to the laboratory. If INR > 1.5 a stat 2mg intra venous Vit K (IVK) is initiated and INR rechecked at 6 hrs and if indicated further IVK is administered. The device costs £ 800 which is one off investment. Each patient will cost £ 6 for the strips and controls. This will avoid potential huge revenue loss and aid better medical practice. Conclusion. By the use of this simple device and its introduction in the A and E department, we can avoid the time lost for the anticoagulation reversal. This will mean improved patient care and compliance with BPT can be achieved in this cohort of NOF fracture patients

Aims: Following hip fracture, a delay to surgery of greater than 24 hours is associated with a higher morbidity and mortality. In our unit, one of the common perceived delays is patients admitted on warfarin. The elective perioperative management of patients on warfarin is well documented. We aimed to define the incidence and delay of patients admitted with hip fractures on warfarin, and how its reversal was managed. Methods: Data was collected prospectively from 14 hospitals who contribute to the Scottish Hip Fracture Database. In addition to the data recorded on the Standardised Audit of Hip fractures in Europe form (SAHFE), specific questions relating to warfarin and its reversal were asked. Results: During 1.8.01–31.12.01, 1641 patients were admitted with a hip fracture, 42 patients (2.6%) were taking warfarin with the commonest indication being atrial fibrillation (40.5%). Mean INR on admission was 2.83 (range 1.2–8.2), and at surgery was 1.43 (range 1.0–2.0). Active reversal occurred in 19 patients. A delay to theatre of > 48 hours occurred in 72.7% of the warfarin group versus 19.0% in the non-warfarin group. There were wound complications in 5 patients taking warfarin. Conclusions: The number of patients admitted on warfarin was lower than we had anticipated. Delay to theatre was significantly higher in the warfarin group. The approach to the perioperative management of patients taking warfarin was varied

Introduction: We found some unusually long delays and repeated canellations in patients on warfarin and associated proximal femur fractures. Aim of our study was to find the safe INR levels at which the patients can be subjected to surgery and if possible determine the approximate time when patients would reach the safe levels based on INR results at admission. Generally an INR level of less than 2.0 is considered safe and there is no set policy within hospitals on advance booking of these patients. Methods: We identified all proximal femur fractures in a one year period in our hospital who were on warfarin, determined the reason for which they were on warfarin. Checked INR, LFTS and Renal function on admission. Patients had daily INR levels done at 6’oclock in morning to determine the suitability for theatre. Results: There were 23 patients of total 437 patients with proximal femur fractures on warfarin. Single most important reason for treatment on warfarin was atrial fibrillation(in 18 patients),other reasons were thromboembolic disease, recurrent pulmonary embolism and heart valve replacement. The INR on admission ranged 1.6–4.0 with a mean of 2.6.We found that most patients with an INR less than 3.0 on admission had acceptable levels within three days of admission whilst those with an INR greater than 3.1 had an acceptable levels within four days. In patients with raised LFTS or renal function impairment took longer time to settle. Conclusion: We recommend that patients with an INR less than 3.0 can be provisionally booked for theatre 3 days from admission while those with an INR 3.1–4.0 can be listed for theatre 4 days from admission except where there is a grossly altered renal or liver function. By listing patients in above method, unexpected cancellations and the practice of keeping the patients fasted on a daily basis can be avoided

Introduction: It was noted that INR levels transiently increased before dropping after stopping warfarin pre-operatively in warfarinised patients with femoral neck fractures. Surgery was more likely to be delayed in these patients. The aim of this retrospective study was to determine the trend of INR level after stopping warfarin and to determine the morbidity and mortality in these patients. Material and Methods: All patients with femoral neck fracture who were on warfarin between 01.01.2002 and 31.12.2003 were included. Case notes and haematology reports were reviewed. Results: 22 (4.2%) out of 533 patients with femoral neck fractures were found to be on warfarin on admission. 21 case notes were obtained. 7 male and 14 females with mean age of 81 years. In 11 (52%) cases, INR level increased before coming down after stopping warfarin. 60% of them had morphine as analgesic compared to 40% in the other group. Average rise in INR was 0.4. Average delay in surgery due to high INR was 3.5 (range 1–8) days. It took average of 4 days to achieve desirable INR after restarting warfarin. 6 (28%) needed blood transfusion. Nine (43%) patients developed complications including: intra-operative bleeding-1, postoperative DVT-1, fast AF-2, post-operative anaemia-1, other medical-3. One patient (5%) died from large CVA 12 days after surgery. No further mortality was found within 30 days of surgery. Conclusion: Incidence of femoral neck fractures on warfarin was 4.2%. In over half of the cases, the INR level went up before going down after stopping warfarin. Morphine may be responsible for this trend. Delay in surgery does not seem to increase mortality or morbidity compared to published studies

Introduction. It is estimated 5% of patients over 65 years receive warfarin therapy. This paper aims to analyse whether a time delay to hip fracture fixation while waiting for the patients International Normalised Ratio (INR) to return to normal increases the mortality risk. Methods. A prospective database of 937 hip fractures was analysed. Patient demographics and time from admission to operation were recorded. The patients' INR on admission and during the preoperative period, the need for vitamin K reversal, and any postoperative thromboembolic compilations were recorded. Thirty-day mortality was obtained from the General Register Office for Scotland. Patients with a therapeutic INR were categorised into two groups: those who received vitamin K within 24 hours of admission and those who did not. Results. There were 27 patients (74% female, mean age 80.9 years) receiving warfarin for atrial fibrillation. Two patients had a subtherapeutic INR on admission and were excluded from further analysis. Nine of eleven patients receiving vitamin K (mean dose 1.3mg) had surgery within 48 hours of admission, whereas only five of the fourteen patients who did not receive vitamin K had surgery within this time (OR3.6, p=0.047). There were no thromboembolic complications during admission for either group. Thirty-day mortality was increased for both groups relative to standard rate (OR1.5, p=0.5, and OR2.4 p=0.2 respectively), but there was no significant difference between the groups (p=0.9). Conclusion. Patients with a fractured hip who are receiving warfarin for atrial fibrillation and have a therapeutic INR should receive low dose vitamin K on admission to facilitate early operative intervention and rehabilitation

Introduction. Peak incidence of pulmonary embolism (PE) typically occurs weeks after total hip (THA) or knee (TKA) arthroplasty, long after hospital discharge. We investigated risk factors for acute PE occurring during index hospitalisation. Methods. Retrospective review of an IRB-approved database identified 329 arthroplasties performed by a single surgeon between 2002 and 2007 at two University teaching hospitals. Warfarin (goal INR 2.0) was standard venous thromboembolism prophylaxis. Results. There were 126 (38.6%) primary THA, 86 (26.1%) primary TKA and 117 (35.3%) revision arthroplasties. Seven patients (7/329; 2.1%) experienced clinically evident non-fatal pulmonary embolism, including 5 after TKA (5/128; 3.9%) and 2 after THA (2/194; 1.0%). In-hospital PE occurred in 4 (1.2%) patients (3 TKA, 1 THA) at a mean 2.7 days (range 2-4 days) after operation, compared with 3 symptomatic events (2 TKA, 1 THA) occurring after discharge (mean 19.3 days; range 8-27 days). Three of four patients suffering acute in-hospital PE were on pre-operative warfarin for chronic atrial fibrillation. Among all patients on pre-operative warfarin, 3 (12.5%) sustained an early PE, with a relative risk of 38.1 times that of controls not on chronic warfarin therapy (p=0.001). Body mass index greater than 30 kg/m2, a history of previous venous thromboembolism, coronary artery disease, ASA score, and type of operation were all found to not be associated with increased risk of in-hospital PE. Conclusion. Acute symptomatic in-hospital pulmonary embolism was correlated with chronic pre-operative warfarin anticoagulation. Compared to historical controls, time to PE was shorter in patients on chronic warfarin. Rebound hypercoagulability after discontinuation of chronic warfarin in preparation for total joint arthroplasty represents a greater hazard than excessive bleeding; we advocate bridging anticoagulation with LMWH in these patients

Post operative warfarinisation of elective arthroplasty patients delays their discharge. We retrospectively analysed all patients who required warfarinisation post surgery from April to September 2011. We identified the number of extra days stayed for the sole purpose of warfarinisation (i.e. after discharge by Physiotherapy and Occupational Therapy) and estimated the cost implications of this extended stay. 76 patients were warfarinised post operation, mean age 70.6 years (50–87) with 42 females and 34 males, 37 THR and 33 TKR. The mean extra days stayed was 3.1 (range 0 to 9). Atrial fibrillation and previous venous thromboembolism (DVT/PE) were the most common indication, 78%, followed by a current episode of DVT/PE, 11%. The nature of joint replacement made no difference to the extra days stayed (3.1 for THR and 2.9 for TKR) or the INR (2.27 in both groups) at discharge. Random loading dose instead of the recommended 5 mg of warfarin resulted in prolonged stay, 4.5 days compared to 3 days otherwise. The approximate cost per inpatient day is £500 (£137 nursing, £163 medical and £200 for facilities). From our results this amounts to £1500 per patient and £228,000 a year. In addition, there is a loss of income as the bed occupancy means not being able to undertake another arthroplasty surgery (£3,600 per patient) and possible failure to achieve waiting time targets. We conclude that substantial financial and resource savings can be made if warfarinisation is undertaken at the community level

Introduction: The purpose of this study was to investigate the effects of combination treatments with anticoagulant (warfarin) and a lipid-lowering agent (probucol) on the prevention of steroid-associated osteonecrosis (ON) in rabbits. Materials and Methods: Male adult Japanese white rabbits were intramuscularly injected once with 20mg/kg body weight of methylprednisolone acetate into the right gluteus medius muscle. These rabbits were divided into three groups: a warfarin plus probucol treatment group (WP Group, n=25), a probucol treatment group (PR Group, n=30), and a non-prophylactic treatment group (NP Group, n=20). Two weeks after the cortico-steroid injection, both femora and humeri were histopathologically examined for the presence of ON, and the sizes of bone marrow fat cells were morphologically examined. Results: The incidence of ON in the WP Group (5%) was significantly lower than that in the NP Group (70%) (p < 0.0001). The incidence of ON in the PR Group (37%) was significantly lower than that in the NP Group (p < 0.05), but it was significantly higher than that in the WP Group (p < 0.01). The mean size of the bone marrow fat cells was significantly smaller in the WP Group (53.5 ± 4.1μm) than that in the NP Group (60.0 ± 4.0μm) (p < 0.0001). There were no significant differences in the size of bone marrow fat cells between the WP and the PR Groups (52.0 ± 5.0μm). Discussion: This study experimentally confirmed that anticoagulant plus lipid-lowering agent treatment has a preventative effect on steroid-associated ON in rabbits

Current orthopedic practice requires consideration of apparently contradictory recommendations regarding VTE prevention among THR/TKR patients. American College of Chest Physicians (ACCP) 8th Clinical Practice Guidelines for the Prevention of Venous Thromboembolism recommend against aspirin for VTE prophylaxis in any patient. 1. The American Academy of Orthopedic Surgeons (AAOS) Guideline recommends pulmonary embolism risk stratification, then implementation of one of many possible courses including the use of aspirin. 2. . We conducted a prospective observational study among consecutive patients presenting for total hip or knee arthroplasty. Pre-operative PE risk stratification was performed at the discretion of the surgeon. Patients identified as usual risk for PE received aspirin. Patients considered being at elevated risk for PE received warfarin. This observational study protocol called for one year of data collection. At approximately 8 months 656 patients were enrolled, and the surgeon principally implementing PE risk stratification and administration of aspirin chose to stop enrolling patients due to a high incidence of pulmonary emboli. One hundred fifty five patients received thromboprophylaxis with aspirin 600 mg PR in the PACU, then 325 mg BID for one month (reduced to 81 mg daily if GI symptoms were present). The remaining 501 patients received an ACCP-based warfarin protocol managed by a pharmacist anticoagulation management service. Our hypothesis is the null hypothesis; that an AAOS-based approach to hromboembolism prevention is not inferior to an ACCP-based approach. The a priori primary endpoints of the AVP Study are clinically overt VTE, DVT, PE, major bleeding, and death. All patients will receive a 90 day follow-up questionnaire in person or by telephone. Additionally, the electronic medical record of Intermountain Healthcare will be interrogated for ICD-9 codes germane to the outcomes of interest. Ninety day follow-up has been completed for approximately 140 patients. The dataset will be locked upon completion of the 90 day follow-up among those patients who last received PE risk stratification and aspirin therapy (data lock early June, 2009). We anticipate preliminary data available for report by July, 2009

Introduction. Pulmonary embolism (PE) complicates up to 1% of total joint arthroplasties (TJA). Many PE treatment guidelines call for immediate initiation of therapeutic anticoagulation. Options include Xa inhibitors, Enoxaparin, and Warfarin. Deciding between these is a balance of the efficacy and the risks. Little data exists regarding the risks of each of these treatment options for treating PE in arthroplasty patients. Methods. We examined the records of 29,270 patients who underwent a primary total joint arthroplasty (TJA), defined as a unilateral total knee arthroplasty (TKA) (18,987) or total hip arthroplasty (THA) (10,283), between 2/2016 and 12/2018 at our institution and identified 338 (242 TKA, 96 THA) patients who developed an in-hospital PE treated with therapeutic anticoagulation. The patients were treated with therapeutic doses of Xa inhibitors, enoxaparin or warfarin. The type and frequency of complications were determined and classified as major or minor. Major complication included: bleeding requiring surgery, GI bleed requiring treatment, >2 unit transfusion and mortality. Minor complications included wound drainage, bleeding not requiring surgery, and thrombocytopenia. Results. Overall complication rates were high for all treatments. Xa inhibitors had the lowest complication rate at 14% compared to 20% for enoxaparin and 20.7% for warfarin though the difference did not quite reach statistical significance (p=.054). Both major and minor complication were lower with Xa inhibitors, but again the difference was not statistically significant (p=0.67). There was no significant difference in complications between TKA groups (p=0.73) or THA groups (p=0.83). Gender and body mass index were not predictive of major or minor complications. Discussion. Our results demonstrate high complication rates associated with modern therapeutic anticoagulation protocols for perioperative PE following TJA. Patients who receive therapeutic anticoagulation postoperatively are at high risk for complication. Xa inhibitors may decrease these risks, but larger studies are required

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

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