Aims. This meta-analysis and systematic review aimed to comprehensively investigate the effects of vitamin K supplementation on bone mineral density (BMD) at various sites and bone metabolism in middle-aged and older adults. Methods. The databases of PubMed, Web of Science, and Cochrane Library were thoroughly searched from inception to July 2023. Results. The results revealed that vitamin K supplementation increased BMD at the lumbar spine (p = 0.035). Moreover, the pooled effects demonstrated a notable increase in carboxylated osteocalcin (cOC) (p = 0.004), a decrease in uncarboxylated osteocalcin (ucOC) (p < 0.001), and no significant effect on total osteocalcin (tOC) (p = 0.076). Accordingly, the ratio of cOC to ucOC (p = 0.002) significantly increased, while the ratio of ucOC to tOC decreased (p = 0.043). However, there was no significant effect of vitamin K supplementation on other bone metabolism markers, such as cross-linked telopeptide of type 1 collagen (NTx), bone alkaline phosphatase (BAP), and procollagen I N-terminal propeptide (PINP). Subgroup analysis revealed that vitamin K notably enhanced bone health in females by increasing lumbar spine BMD (p = 0.028) and decreasing ucOC (p < 0.001). Vitamin K, especially vitamin K2, exhibited effects on maintaining or increasing lumbar spine BMD, and influencing the balance of cOC and ucOC. Conclusion. This review suggests that the beneficial effects of vitamin K supplementation on bone health primarily involve enhancing the carboxylation of OC rather than altering the total amount of OC. Cite this article: Bone Joint Res 2024;13(12):750–763

Aims: The use of vitamin K was proposed in the treatment of osteoporosis. Some experimental studies suggested that vitamin K might promote mesenchymal stem cells (MSCs) differentiation into osteoblasts progenitors and inhibit osteoclasts formation. In the present study we analysed the effects of vitamin K at different concentrations on human mesenchymal stem cells derived from fracture callus. Methods: MSCs were obtained from the fracture’s site of three patients during surgical operation of osteosynthesis. Cells were grown on plastic plates in DMEM, 10% foetal bovine serum (FBS), 1% penicillin-streptomycin, 1% fungizone, 5mM beta-glycerophosphate and 50 microg/ml ascorbic acid. Half of the samples was incubated with vitamin D (10 nm) and K at different concentrations (1, 3, 10 microM). Proliferation rate (MTT colorimetric assay) and cell differentiation (FACSCalibur flow cytometry) were assessed at 3, 10 and 20 days. Immunocytochemical analysis (not-carboxylated osteocalcin and carboxylated osteocalcin) was also performed. Results: MSCs stimulated with vitamin K and D expressed higher levels of osteoblastic markers than controls at 3, 10 and 20 days of colture. Conclusions: This study confirmed the results obtained in previous in vitro experiments: vitamin K has osteoinductive properties on MSCs derived from fracture callus and it could play a role in reparative osteogenesis in vivo

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. 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

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

Background and Aims. Many orthopaedic patients admitted to hospital who require urgent surgery are also on Warfarin. Patients with an INR>2 have an increased risk of bleeding complications during surgery; however delay to surgery due to a high INR has both clinical and financial implications. This audit evaluates whether the appropriate management for correction of INR is employed as per local guidelines and, if not, whether this results in significant delay to operative treatment. Methods. A retrospective and prospective audit was performed analysing all Orthopaedic trauma admissions admitted to University Hospital Aintree in a 5 month period. Only those solely on warfarin, who were not acutely bleeding and required surgery in <24 hours were included. Results. A sample of 17 patients was obtained of which only 35.3% had correct INR reversal as per local guidelines. Errors that occurred included 81.1% not being given further Vitamin K at reassessment, 18.2% given too much Vitamin K, 9.1% given too little Vitamin K, 18.2% given Octaplex incorrectly and 9.1% not given Octaplex when indicated. Only 1 patient had a delay to their surgery directly resulting from incorrect INR reversal (total time to surgery − 33 hours 45 minutes). Conclusion. Better education for clinical staff on the local policy for INR reversal in patients requiring urgent orthopaedic surgery is needed. Local policy guidelines have since been redesigned in light of these results and a completion audit cycle has been performed showing significant improvement with 50% of the patient sample given correct INR reversal

There is currently wide variation in the management of patients who are anticoagulated with Warfarin and require urgent orthopaedic surgery. These form an important and significant group of patients, in terms of real numbers (at least 5,600 per annum in the UK). A study was initiated with an audit of 34 patients presenting to the West Wales unit who were warfarinised at admission and required trauma surgery. Observations were recorded about their pre-operative management and the delay this caused in taking the patient to theatre. 6 months later, a similar group of patients were re-audited. The mean delay to surgery in those patients in whom the INR was left to fall spontaneously was 5.5 days. Following administration of 1mg i.v. Vitamin K in those patients without cardiac valves, re-audit showed the mean delay reduced to 2.2 days. Representations from at least 6 major specialties were considered and a consensus statement was derived. Standardised protocols, which hinge on whether or not the patient has or does not have a cardiac valve were devised. Vitamin K should not be given to those patients with a cardiac valve and early consultation with cardiology and anaesthetics is recommended, with consideration of referral to a specialist cardiothoracic unit. For those patients without a cardiac valve, 1mg of Vitamin K may be administered, repeated as necessary until the INR is less than 1.8. Intravenous Heparin should be provided in the interim whilst the patient is waiting for surgery. This is discontinued the morning of surgery and subcutaneous Heparin reinstated post-operatively. These recommendations have been trialled in the two units involved in the study and have been relatively safe and easy to implement

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

Venous thromboembolism (VTE) prophylaxis following total joint arthroplasty (TJA) should be individualised in order to maximise the efficacy of prophylactic measures while avoiding the adverse events associated with the use of anticoagulants. At our institution, we have developed a scoring model using the Nationwide Inpatient Sample (NIS) database, which is validated against our institutional data, to stratify patients into low- and high-risk groups for VTE. Low-risk patients are placed on aspirin 81 mg twice daily for four weeks post-operatively, and high-risk patients are placed on either a Vitamin K antagonist (warfarin), low molecular weight heparin, or other oral anticoagulants for four weeks post-operatively. All patients receive sequential pneumatic compression devices post-operatively, and patients are mobilised with physical therapy on the day of surgery. Patients who have a history of peptic ulcer disease or allergy to aspirin are also considered for other types of anticoagulation following surgery. Risk Stratification Criteria. Major comorbid risk factors utilised in our risk stratification model include history of hypercoagulability or previous VTE, active cancer or history of non-cutaneous malignancy, history of stroke, and pulmonary hypertension. We consider patients with any of these risk factors at elevated risk of VTE and therefore candidates for formal anticoagulation. Other minor risk factors include older age, bilateral surgery compared with unilateral, inflammatory bowel disease, varicose veins, obstructive sleep apnea, and history of myocardial infarction, myeloproliferative disorders, and congestive heart failure. Each minor criterion is associated with a score. The cumulative score is compared with a defined threshold and the score that surpasses the threshold indicates that the patient should receive post-operative anticoagulation. To facilitate the use of this scoring system, an iOS mobile application (VTEstimator) has been developed and can be downloaded from the app store

Best Practice Tariff (BPT) recommends operation for hip fracture within 36 hours. Anticoagulation reversal often delays this. Audit of our service, to establish the impact on BPT of anticoagulation reversal, showed a loss of revenue and delays. Subsequently an ‘early trigger’ Intravenous Vitamin K (IVK) pathway was introduced and re-audit completed. Hip fracture patients admitted over a 32-month period were reviewed. Primary outcome was time to theatre for warfarinised and non-warfarinised patients. This was analysed using independent t-tests. A change in practice, involving nurse led administration of 2mg IVK in the Emergency Department prior to knowledge of the coagulation screen, was instigated. Three months later a re-audit occurred. In the first audit cycle, 83 patients were admitted on warfarin with a median time to theatre of 49.7 hours. 21% of these patients gained BPT. Following protocol change, over three months, 14 warfarinised hip fracture patients were admitted. Twelve patients achieved satisfactory reversal; eight with one IVK administration. Median time to theatre was 33.9h. Compliance with BPT in terms of delay due to anticoagulation was 86%. Our audit demonstrates that ‘early-trigger’ IVK reduces delays to theatre and helps reduce BPT related financial loss. It enables high quality patient-centred care within financial constraints

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

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

Aims

Factors associated with high mortality rates in geriatric hip fracture patients are frequently unmodifiable. Time to surgery, however, might be a modifiable factor of interest to optimize clinical outcomes after hip fracture surgery. This study aims to determine the influence of postponement of surgery due to non-medical reasons on clinical outcomes in acute hip fracture surgery.

According to the 2004 ACCP guidelines on antithrombotic and thrombolytic therapy general extended prophylaxis with low molecular weight heparins, vitamin K antagonists, or fondaparinux is recommended after major orthopedic surgery. This recommendation is based on a number of placebo controlled, clinical studies using venographic screening for deep vein thrombosis (DVT), as a surrogate end-point for pulmonary embolism (PE), other vascular thrombotic events were not considered. In a recent meta-analysis on these studies the overall event rate of symptomatic venous thromboembolism 30–42 days after a joint arthroplasty was 2.7% DVT and 0.6 % PE in patients having short-term prophylaxis and it was significantly reduced by extended prophylaxis. Bleeding episodes were seen in 4% of cases having extension. Taking into consideration the risk benefit for the individual patient do these findings justify that extended prophylaxis is used on a general basis? To answer this question also compliance, adverse event profile, and cost of the prophylactic regimens have to be addressed. It would be very attractive to be able to individualize the duration of the prophylactic period by assessing the thrombotic potential of every patient in order to balance the risks and benefits of continued prophylaxis

Fractures of the Proximal Femur are a common and disabling injury requiring hospital admission and surgical treatment leading to approximately 86,000 inpatient episodes annually in the UK, with such patients occupying more than 20% of NHS orthopaedic beds. Based on current trends the number of hip fractures may rise to 120,000 per annum by 2015. As the age of the population increases, so does the prevalence of concomitant medical conditions. Atrial Fibrillation is rising in the general population. Recently, the benefit of treating these patients with warfarin to prevent stroke has been shown; as a consequence, the number of patients being treated with warfarin is on the increase. We have performed a retrospective study of all patients admitted to our unit with Fractures of the neck of the femur between 2001 and 2006, from the Accident and Emergency department with a primary diagnosis of Proximal Femoral Fracture (1987 patients). 138 patients were on long term warfarin at the time of their admission (6.9% of admissions). 90.4% were being warfarinised for AF, 7.6% for DVT and the rest for other indications. Of these Patients only 12 (8.7%) received active reversal to their warfarin. (All received vitamin K either orally or Intravenously). The average delay to theatre attributable to warfarin therapy was 41.1 hours (p-0.001). Active reversal allowed this delay to be negated (p-0.01), and did not delay the reloading of warfarin post-operatively (p-0.012). It also allowed an average of 10.2 days earlier discharge from the orthopaedic unit (p-0.001). This study shows that significant delays occur because of Warfarinisation of these patients and that active reversal seems to be beneficial in expediting surgical treatment and discharge from the orthopaedic unit

Major orthopaedic surgeries such as total hip and total knee replacements are considered a major risk factor for venous thromboembolism (VTE). Without prophylaxis, DVT occurs in 10–40% of general surgical or medical patients and 40–60% of patients following major orthopaedic surgery. There has, however, been a perception that VTE is less common in Asia than in Western countries. New evidence has emerged recently that contradicts this perception. Results from multinational epidemiological studies (SMART, AIDA, ENDORSE) clearly showed that the rate of venographic and symptomatic thrombosis after major joint replacement in Asian patients is similar to that previously reported in patients in Western countries. However, thromboprophylaxis is not routinely used in Asia, even in situations considered high risk in Western countries. The ENDORSE study reported that less than 20% of at-risk surgical patients in Asia received prophylaxis compared with over 80% in Western countries. This leaves the majority of patients at risk of developing VTE and VTE-related conditions, which continues after hospital discharge. Current guidelines recommend the use of thromboprophylaxis for at least 10 days and up to 35 days in patients undergoing total joint replacement. Available anticoagulants are effective at preventing VTE but are associated with various limitations, such as parenteral administration as in the case of UFH and LMWH. A narrow therapeutic window, unpredictable pharmacology, frequent coagulation monitoring and dose-adjustment as in the case of vitamin K antagonists (VKAs). Several new, oral anticoagulants are in advanced clinical development, including the direct thrombin inhibitor, dabigatran, and the direct Factor Xa inhibitors, rivaroxaban and apixaban

Aim: Evaluate the incidence of complications related to timing (time between admission ad operation) and oral antiplatelet/anticoagulant therapy in patients treated for a hip fracture. Materials and Methods: We prospectively evaluated 5 groups of 30 patients each, selected out of 875 consecutive patients admitted at the First Aid Unit of our Hospital with a proximal femoral fracture: group A – patients on Warfarin therapy, treated more than 5 days after admission (in order to allow the wash-out of Warfarin, as advised by many Anaesthesiologist Associations); B – patients treated more than 5 days after admission, not on Warfarin therapy; C – patients treated less than 48 hours after admission, not on Warfarin therapy; D – patients on Aspirin/NSAIDS therapy, treated more than 5 days after admission; E – patients on Ticlopidine/Clopidogrel therapy, treated more than 5 days after admission. The groups were comparable regarding age, gender, pre-trauma walking ability, mental state, fracture type and treatment. Blood loss, number of RBC transfusions, complications during hospitalization and up to 6 months after discharge, duration of hospitalization, degree of functional recovery and 2 years mortality were recorded. Statistical analysis included Kruskall-Wallis, U-Mann-Whitney and Logistic Regression Tests (SPSS 13.0 software). Results: Group A showed higher preoperative blood loss (p=0.002), and longer hospitalization (p< 0.001), compared to all other groups. Groups D and E showed no higher complication and mortality rate in comparison to group B and C, while group A showed higher complication and mortality rate. Standing alone, timing and Warfarin appear not to be significant risk factors, while taken together they represent a high risk factor for complications ad mortality (p=0.009). Conclusion: Patients on Warfarin therapy, affected by hip fracture, are at high risk of complications and mortality, if the recommendation of postponing treatment until drug wash-out is accepted. Reversal of anticoagulation using vitamin K and straight-forward treatment should be considered. Antiplatelet therapy appears not to have the same adverse effect as anticoagulant therapy

The selection of venous thromboembolism (VTE) prophylaxis after total joint arthroplasty (TJA) has been controversial. Although the aspirin controversy is presumably resolved, there is no medical evidence for the “optimal” VTE prophylaxis regime for individual patients. A risk-stratified multi-modal VTE prophylaxis protocol was developed and adopted by consensus. VTE risk factors and bleeding risk factors were categorised into six VTE/bleeding risk levels: (1) pre-operative vitamin K antagonists (VKA) use, (2) bleeding risk factors, (3) hypercoagulable state, (4) pre-operative anti-platelet therapy [clopidogrel use], (5) VTE risk factors, (6) no VTE or bleeding risk factors. The pharmacologic agents used for each risk level were: (1) resume VKA with low molecular weight heparin (LMWH) bridge, (2) pharmacologic agents contra-indicated and mechanical prophylaxis only, (3) VKA for 90 days with LMWH bridge, (4) resume anti-platelet therapy, (5) LMWH in hospital and discharge on aspirin for 90 days, (6) aspirin for 90 days (starting in hospital). In addition to pharmacologic treatment, all patients received multi-modal prophylaxis including early mobilisation, mechanical foot pumps, and neuraxial anesthesia when not contra-indicated. Prior to surgery, a VTE/bleeding risk factor checklist was completed determining the risk level. The intervention cohort included all TJA patients from January 1, 2010 to December 31, 2012. The comparison cohort included all TJA patients from the year prior to implementation of the protocol at the same community hospital. Thirty day all-cause non-elective re-admissions, 30 day same-site re-operations, 90 day VTE events, and protocol compliance were abstracted from the electronic medical record. The intervention group consisted of 2679 patients (1075 hip arthroplasty patients and 1604 knee arthroplasty patients). The comparison group consisted of 1118 patients (323 hip arthroplasty patients and 795 knee arthroplasty patients). The 30 day all cause non-elective re-admission rate was 2.72% (73/2679) in the intervention group and 4.29% (48/1118) in the comparison group (p=0.0148). The 30 day same-site re-operation rate was 1.38% (37/2679) in the intervention group and 1.25% (14/1118) in the comparison group (p=0.8773). The 90 day VTE event rate was 1.57% (42/2679) in the intervention group and 3.40% (38/1118) in the comparison group (p=0.0007). The VTE rate was higher for knee arthroplasty patients 2.00% (32/1604) than for hip arthroplasty patients 0.93% (10/1075) (p=0.0379). The rate of VTE events was higher for patients that deviated from the VTE protocol 5.03% (10/199) than for all risk groups treated per the protocol 1.29% (32/2481) (p=0.0007). The risk-stratified multi-modal VTE prophylaxis protocol simultaneously reduced 30 day all-cause non-elective re-admissions and 90 day VTE events. The possible causes for reducing 30 day re-admissions and reducing 90 day VTE events are: (1) reducing bleeding events by using aspirin for VTE prophylaxis in more than 80% of patients, (2) extending VTE prophylaxis to 90 days, and (3) using multi-modal prophylaxis. The risk-stratified multi-modal VTE prophylaxis protocol for total joint arthroplasty is consistent with 9 of the 10 recommendations in the AAOS Clinical Practice Guideline. The risk-stratification checklist provides a standardised tool to assess risks, discuss risks, and make shared decision with patients. Patient treatment that deviated from the protocol had a significantly higher VTE rate (5.03%). Protocol compliance increased each year from 91.1% in 2010 to 94.2% in 2012

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

Introduction. Haemostasis is a vital, complicated process. Many standard orthopaedic operations strain the limits of this process, leading to blood transfusions. The former view is that haemostasis occurs cascade-wise in discrete steps, primary haemostasis followed by coagulation, followed by fibrinolysis. This view has been modified to the insight that although there is a temporal succession of these steps, there is also multiple ante- and retrograde interactions between the various reactions. The complexity of the haemostatic system also implies individual variance of the effectiveness of haemostasis. Minor haemostatic defects such as mild cases of von Willebrand disease probably occur in several per cent of the population. Furthermore many orthopaedic patients are on medication with ASA, NSAIDs, clopidogrel, antidepressants, warfarin and LMWH, all common drugs which affect haemostasis. Methods to reduce blood loss. Basal measures include avoidance of hypothermia, appropriate positioning of the patient, appropriate anesthesiological and surgical techniques and if possible discontinuation of unsuitable drugs. In patients with known haemostatic disorders, substitution of the deficient coagulation factors may improve haemostasis. The same holds true for patients on warfarin medication where substitution with vitamin K, with factors of the vitamin-K dependant complex or with plasma normalizes haemostasis. Desmopressin stimulates the release of factor VIII and the von Willebrand factor and thus improves platelet function in some subgroups of von Willebrand disease and in platelet dysfunction due to ASA or dextran use. However, the blood-saving effect in patients without these disorders has not been conclusively shown. In recent years the role of factor VII as a main initiator of coagulation has been stressed. Case reports of effective haemostasis in severe trauma using recombinant factor VII have been published but the experience of its use in orthopaedic surgery is so far limited and the cost is prohibitive for routine use. During surgery and trauma, the fibrinolytic system is activated with particularly high levels of fibrinolytic markers in the wound. The effect of tranexamic acid, a synthetic fibrinolysis inhibitor has been studied in 17 randomised control trials in knee and hip arthroplasty. The drug significantly reduced blood loss and/or blood transfusion in the majority of these studies. The same findings were reported in 2 studies in spinal surgery. To exert full effect, tranexamic should be given prophylactically, before the beginning of surgery. In studies at our department, the use of tranexamic acid was highly costeffective as it is significantly cheaper than blood transfusions. Aprotinin, a protease inhibitor decreasing fibrinolysis has been extensively used in cardiac surgery. It has also been shown to reduce blood loss and blood transfusion in 4 out of 5 RCT:s in major orthopaedic surgery. Neither aprotinin nor tranexamic acid were reported to increase the frequency of postoperative venous thromboembolism. Fibrin sealant, sprayed onto the wound has also been reported to reduce bleeding in spinal surgery as well as in arthroplasties. Conclusion It is important to reduce blood loss and the burden of transfusion in orthopaedic surgery. This can be achieved by some simple basal methods as well as by the aid of various drugs to ameliorate haemostasis. At present, tranexamic acid seems to be the most costefficient drug for routine use