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

Osteoporosis is one of the most common diseases in modern aging society. Receptor activator of nuclear factor-κB ligand (RANKL) plus macrophage colony stimulating factor (M-CSF)-mediated osteoclastogenesis has been recently implicated in the pathogenesis of this disease. Among other causes, the anticoagulant drug heparin is a notable inducer of secondary osteoporosis, although the molecular pathway underlying this process, particularly in human model, has not been clarified yet. Recently, we reported the differentiation of two subtypes of osteoclasts starting from human peripheral blood CD14-positive monocytes (Monocytes), respectively fusion regulatory protein-1 (FRP-1/CD98)-mediated osteoclasts and RANKL+M-CSF-mediated osteoclasts. We, therefore, investigated in details effects of heparin on differentiation and activation using a simple system of human osteoclastogenesis. When Monocytes were cultured with osteoclastogenesis-relating factors and a high dose of heparin, heparin suppressed osteoclastogenesis in both pathways. However, a proper quantity of heparin enhanced tartrate-resistant acid phosphatase-positive multinucleated giant cell formation. There were significant differences in fusion indices between control osteoclasts and osteoclasts stimulated by moderate concentrations of heparin in two systems (P< 0.05). As a result of osteoclastic activity, FRP-1-mediated osteoclasts treated with a proper quantity of heparin formed larger pits on Ca plates. Moreover, lacunae on dentin surfaces induced by FRP-1-mediated osteoclasts were enhanced with moderate concentration of heparin. In contrast, heparin did not increase pit-formation area on Ca plates and on dentin surfaces by RANKL+M-CSF-mediated osteoclasts. Evaluating the relation between the concentration of heparin and the osteolytic areas on Ca plates, Pearson’s correlation coefficient of the FRP-1 and the RANKL+M-CSF were −0.973 (P< 0.05) and −0.695 (P=0.19), respectively. In present study, although moderate doses of heparin stimulated differentiation in both systems, in osteoclastic activity, heparin promoted only to the FRP-1 system, not to RANKL+M-CSF system. Our results suggested FRP-1-induced osteoclastogenesis mainly contributes to development of heparin osteoporosis and also that the onset mechanism after long-term administration of heparin may be affected by the characteristic bone resorption ability of FRP-1osteoclasts

The clinical application of bone morphogenetic proteins (BMPs) offers solutions to many challenging problems in orthopaedics. However, a practical clinical problem is to obtain a controlled release of the BMPs. The attachment of heparin to biomaterials may result in an appropriate matrix for the binding, and sustained release of BMPs. Binding of growth factors to heparin stabilizes these growth factors, protects them from proteolytic degradation, and prolongs the half-life of BMPs in culture media 20-fold. We created a carrier based delivery system with a localized sustained release by loading a tricalciumphosphate/hydroxyapatite (TCP/HA) bone substitute coated with cross-linked collagen and heparin, with BMP-7. TCP/HA granules (BoneSave. ™. , Stryker Orthopaedics) were coated with collagen, and subsequently the collagen was cross-linked in the presence (TCP/HA-Col-Hep) and absence (TCP/HA-Col) of heparin. BMP-7 was loaded onto the coated TCP/HA granules. Morphology of the coated collagen with and without heparin, and release kinetics of BMP-7 from the granules were analyzed. TCP/HA granules without coating were used as controls. Analysis showed a highly porous collagen network on both TCP/HA-Col and TCP/HA-Col-Hep granules. Immersion of the granules in BMP-7 solution, resulted in the binding of 54±3% (62.9±5.4 ng BMP-7/mg granule) to the TCP/HA granules, 64±8% (69.0±9.6 ng BMP-7/mg granule) to the TCP/HA-Col granules, and 78±1% (92.9±4.8 ng BMP-7/mg granule) to the TCP/HA-Col-Hep granules. TCP/HA granules showed a burst release of BMP-7 within the first 4 h. TCP/HA-Col granules showed an initial burst release, followed by a more gradual release. In contrast, BMP-7 release from the TCP/HA-Col-Hep granules was sustained up to 21 days. The sustained delivery system for BMP-7 developed in this study may provide a powerful tool for bone regeneration. This system could probably also be applied to deliver multiple growth factors that have affinities for heparin, which could for instance synergistically enhance osteogenesis by increasing vascularity

To compare the incidence of Bone Cement Implantation Syndrome (BCIS), perioperative thromboembolic events and mortality in patients with a femoral neck fracture (FNF) treated with a hybrid total hip arthroplasty (THA) without intraoperative unfractioned heparin (UFH) (control) versus a group of patients who received intraoperative UFH before femoral cementation. We retrospectively reviewed 273 patients who underwent hybrid THA due to a FNF between 2015 and 2020. We compared a group of 139 patients without intraoperative administration of UFH (group A) with 134 patients who underwent THA with intraoperative administration of 10 UI/kg UFH (group B). UFH indication was dependent on surgeon´s preference. We assessed the advent of BCIS and 30-day thromboembolic events, as well as 90-day and 1-year mortality. BCIS was observed in 51 cases (18%), defined as Grade 1 (O2% < 94% or fall in systolic blood pressure of 20% to 40%) in 37 cases (13%) and Grade 2 (O2% < 88% or fall in systolic blood pressure of > 40%) in 14 cases (5%). Forty-seven BCIS (35%) were observed in the group that received UFH and 4 BCIS (3%) in the control group (p <0.001). Multivariate regression model showed that intraoperative UFH (OR=18, CI95% 6–52) and consumption of oral anticoagulants (OR=3.3, CI95% 1–10) had an increased risk of developing BCIS. Five patients developed a pulmonary embolism in the UFH group while 2 patients presented this complication in the non UFH group (p=0.231). Mortality was 1% for both groups at 90 days PO (p= 0.98), 2% at 1 year for group A and 3% for group B (p =0.38). BCIS in our series was 18%. We found a paradoxically 17-fold significant increase of BCIS with the use of UFH. Heparin did not prevent BCIS, thromboembolic events and mortality in this group of patients

The Hospital (Trust) guidelines generally recommend 40mg of Low molecular weight heparin (LMWH) twice daily (BD) for all patients over 100kg for those undergoing total hip (THR) and knee replacements (TKR) respectively. British National Formulary (BNF) recommends 40mg of LMWH once daily (OD) for all patients regardless of their overall weight or body mass index (BMI). We evaluated the outcome of prophylactic LMWH dosage for patients undergoing THR and TKR by monitoring surgery related venous-thromboembolic events up to a minimum of three months after surgery. A retrospective audit was carried out after obtaining institutional approval and all consecutive elective patients weighing over 100kg and undergoing THR and TKR were included. All patients were followed up for a minimum of 3 months after their operation to investigate the dose of prophylactic LMWH received, and whether they had developed any venous thromboembolic events (VTE) post operatively. This was done using a combination of electronic notes, drug charts and deep venous thrombosis (DVT) or computed tomography pulmonary angiogram (CTPA) reports on the hospital/trust database. A total of 53 patients underwent elective THR (18) and TKR (35) between the period of March 2017 and September 2017. Forty-four patients received 40 mg OD and 9 patients had 40 mg BD. None of the patients developed a confirmed DVT or pulmonary embolism in the 3 months following surgery regardless of the dose received. We demonstrate that there is no clinical benefit in having patients over 100kg on twice daily LMWH with the aim of preventing post-op thromboembolic complications. This conclusion is in line with the BNF recommendations for VTE prophylaxis

Purpose: The report of a case o f a patient, who underwent a total hip arthroplasty and sustained cerebral hemorrhage due to low molecular weight heparin. Case report: A 46-years-old woman had a total hip replacement due to secondary osteoarthritis after a congenital hip dislocation. She had a free medical record. Treatment with LMWH started the day of the surgery. The patient was dismissed from the hospital the sixth postoperative day, being well, and came back the ninth postoperative day, complaining of hypertension, headache and motor disturbances of her left upper limb. Neurological examination did not revealed any particular findings except reduced strength of her left upper limb. A brain CT scanning showed no significant findings, while her blood platelet count was126000 while immediately postoperatively was 180000 and preoperatively 220000. The following day the patient established a paresis of her left arm and the platelet count fell to 35000, while a new CT scan, revealed small hemorrhages in both parietal cortexes of the brain. LMWH was discontinued. The patient deceased the 11th postoperative day. Conclusion: Heparin Induced Thrombocytopenia type II and hemorrhage due to LMWH is very rare but should be bared in mind from the orthopaedic surgeon who uses LMWH for DVT prophylaxis. Clinical suspicion mandates immediate discontinuation of the agent and consideration of an alternative anticoagulation therapy along with general support of the patient

Aim. Thromboprophylaxis in total hip replacement (THR) and total knee replacement (TKR) remains controversial, conspicuous by absence of consensus. Because of protracted and variable mobilisation, there is an extended risk of Venous Thromboembolism (VTE). We hypothesised that a combination of low molecular weight heparin and miniwarfarin would minimise the initial and extended risk. Therefore we evolved a protocol of enoxaparin sodium 40 mgs for 5 days starting preoperatively and miniwarfarin 1-2mg for 6 weeks following surgery. We undertook a retrospective study of total hip and knee replacements in a District General Hospital between January 2000 and December 2005 to determine the effectiveness of the protocol. Methods. We analysed the incidence of symptomatic VTE in 1307 patients, of who 681 underwent THR and 626 TKR. We evaluated the incidence of symptomatic DVT and PE between 0-6 weeks, 6 weeks-3months and 3-6 months following surgery. Results. Total incidence of VTE in the study group as a whole including both total hip and knee arthroplasty in 6 months following surgery was 29/1307 (2.22%), after THR 12/681 (1.76%) and after TKR 17/626 (2.72%). VTE at 6 weeks following TKR was 12/626 (1.92%) and THR 4/681(0.59%); between 6 weeks-3 months following TKR 1/626 (0.16%) and THR 6/681 (0.88%); between 3- 6 months 4/626 (0.64%) following TKR and 2/681 (0.29%) after THR. DVT following TKR was 12/626 (1.92%) at 6 months and following THR 7/681 (1.03%). PE at 6 months after TKR was 5/626 (0.80%) and THR 5/681(0.73%) with no attributable mortality. Conclusions. The incidence of VTE using our thromboprophylaxis protocol - low molecular weight heparin (LMWH) and very low dose warfarin - in THR and TKR not only compares favourably with other modes of thrombo-prophylaxis in literature, but also is cheap and cost effective

In a prospective study of 205 consecutive patients undergoing surgical stabilisation of acute pelvic and/or acetabular fractures, the incidence of proximal deep vein thrombosis (DVT) was 9.2%, pulmonary embolism (PE) was 1.9% and fatal PE 0.5%. Use of a DVT prophylaxis protocol, using a low molecular weight heparin (LMWH), administered within 24 hours of injury or achieving haemodynamic stability, was associated with a significantly lower incidence of thromboembolism (p=0.036). Increased rates of thromboembolism were associated with longer delays to surgery (p=0.013), delays to mobilisation of the patient post-operatively (p=0.017), delay in starting chemoprophylaxis (p=0.039) and higher injury severity scores (p=0.042). Patient age, sex, Glasgow Coma Scale and fracture classification were not associated with the development of thromboembolic complications. One hundred and thirty four patients had a pre-operative venous Doppler, seven patients had a proximal DVT identified of which six patients had a preoperative inferior vena caval filter applied and underwent successful surgical fracture stabilisation. Five filters were unable to be removed postoperatively and the patients remain on lifelong warfarin. A DVT prophylaxis protocol using LMWH is reported that is safe and effective

There is little in the recent literature about the place of low molecular weight heparin (LMWH) in routine lumbosacral surgery. This study aimed to determine firstly the risk of deep vein thrombosis (DVT) if Clexane was not given preoperatively, and secondly the complications associated with the use of the drug. In a prospective study undertaken from January 2001 to April 2001, 64 patients scheduled for routine lumbosacral surgery were entered. We excluded patients with a high risk of DVT. The mean age of patients was 51 years (16 to 75). Patients were randomly selected to receive Endoxaparin (Clexane) preoperatively the night before (38 patients in group 1) or Clexane postoperatively (26 patients in group. 2). All patients were evaluated by Doppler sonography pre-operatively, four days postoperatively and at six weeks. Blood loss was monitored intra-operatively and postoperatively. Clexane was administered only for eight days. Posterior lumbosacral spinal procedures only were done on 44 patients, while seven had combined anterior-posterior surgery and 13 anterior procedures only. Mean intra-operative and postoperative blood losses in group 1 were twice those in group 2, and patients in group 1 tended to bleed for longer. Two cases of partial thrombosis were seen, both group 1. In group 1 intraspinal haematoma formation was seen in four patients, two of whom required additional surgery. LMWH should not be given preoperatively for routine spinal cases. In fact, it is contra-indicated

Low molecular weight heparin (LMWH) is frequently used as thromboprophylaxis after major orthopaedic surgery. Varying levels of non-adherence (5% to 45%) with outpatient LMWH has been reported. Oral direct thrombin inhibitors have been recommended by industry due to ease of administration. We aim to audit the compliance rate with outpatient LMWH treatment following primary total hip arthroplasties (THA) in our district general hospital (DGH). Using the ORMIS computer system, we identified all primary THA performed in Monklands Hospital between July 2011 and August 2012. Patients’ case notes were analysed retrospectively, looking at operating surgeon's postoperative thromboprophylaxis instructions. We then conducted a telephone interview on patients discharged with outpatient LMWH to assess compliance. There were 58 primary THAs performed during the audit period. 33 patients were discharged on outpatient LMWH, whilst 15 patients and 3 patients were discharged on aspirin and warfarin respectively. Seven patients were excluded as their discharge prescriptions were missing. We successfully contacted 20 of the 33 patients discharged with outpatient LMWH. All respondents showed 100% compliance to the full course of treatment. 50% of patients self-administered; 30% were administered by district nurses and 20% by family members. 35% of patients preferred an oral tablet alternative, for its perceived ease of administration. Bruising and skin irritation were the reported problems in some patients, but these did not affect compliance. Contrary to the previous published non-adherence rates, the compliance rate with outpatient LMWH after THA was high in our DGH. The patient counseling, and family/district nurse involvement in may have contributed to this. However, our numbers of patients are low but data collection continues

Introduction. The National Institute for Health and Clinical Effectiveness recommends both low molecular weight heparin (LMWH) and Rivaroxaban for venous thromboembolic (VTE) prophylaxis following lower limb arthroplasty. Despite evidence in the literature that suggests Rivaroxaban reduces VTE events, there are emerging concerns from the orthopaedic community regarding an increase in wound complications following its use. Methods. Through the orthopaedic clinical directors forum, Trusts replacing LMWH with Rivaroxaban for lower limb arthroplasty thromboprophylaxis during 2009 were identified. Prospectively collected Hospital episode statistics (HES) data was then analysed for these units so as to determine rates of 90-day symptomatic deep venous thrombosis (DVT), pulmonary thromboembolism (PTE), major bleed (cerebrovascular accident or gastrointestinal haemorrhage), all-cause mortality, and 30-day wound infection and readmission rates before and after the change to Rivaroxaban. 2752 patients prescribed Rivaroxaban following TKR or THR were compared to 10358 patients prescribed LMWH. Data was analysed using odds ratios (OR). Results. There were significantly more wound infections in the Rivaroxaban group (3.85% vs. 2.81%, OR=0.72; 95% CI 0.58-0.90). There were no significant differences between the two groups for PTE (OR=1.52; 0.77-2.97), major bleed (OR=0.73; 0.48-1.12), all-cause mortality (OR=0.93; 0.46-1.87) and re-admission rate (OR=1.21; 0.88-1.67). There were significantly fewer symptomatic DVTs in the Rivaroxaban group (0.91% vs. 0.36%, OR=2.51; 1.30-4.82). Conclusion. This study is the first to describe the real impact of the use of Rivaroxaban in the NHS. When compared with LMWH in lower limb arthroplasty patients, wound infection rates were significantly higher following Rivaroxaban use whilst providing no reduction in symptomatic PTE or all-cause mortality

Background. The National Institute for Health and Clinical Effectiveness recommends both low molecular weight heparin (LMWH) and Rivaroxaban for venous thromboembolic (VTE) prophylaxis following lower limb arthroplasty. Despite evidence in the literature that suggests Rivaroxaban reduces VTE events, there are emerging concerns from the orthopaedic community regarding an increase in wound complications following its use. Methods. Through the orthopaedic clinical directors forum, Trusts replacing LMWH with Rivaroxaban for lower limb arthroplasty thromboprophylaxis during 2009 were identified. Prospectively collected Hospital episode statistics (HES) data was then analysed for these units so as to determine rates of 90-day symptomatic deep venous thrombosis (DVT), pulmonary embolism (PE), major bleed (cerebrovascular accident or gastrointestinal haemorrhage), all-cause mortality, and 30-day wound infection and readmission rates before and after the change to Rivaroxaban. 2752 patients prescribed Rivaroxaban following TKR or THR were compared to 10358 patients prescribed LMWH. Data was analysed using odds ratios (OR). Results. There were significantly more wound infections in the Rivaroxaban group (3.85% vs. 2.81%, OR=0.72; 95% CI 0.58–0.90). There were no significant differences between the two groups for PE (OR=1.52; 0.77–2.97), major bleed (OR=0.73; 0.48–1.12), all-cause mortality (OR=0.93; 0.46–1.87) and re-admission rate (OR=1.21; 0.88–1.67). There were significantly fewer symptomatic DVTs in the Rivaroxaban group (0.91% vs. 0.36%, OR=2.51; 1.30–4.82). Discussion. This study is the first to describe the real impact of the use of Rivaroxaban in the NHS. When compared with LMWH in lower limb arthroplasty patients, there were fewer DVTs in the Rivaroxaban group. However, wound infection rates were significantly higher following Rivaroxaban use whilst providing no reduction in symptomatic PE or all-cause mortality

Background. The most appropriate form of chemical thromboprophylaxis following knee replacement is a contentious issue. Most national guidelines recommend the use of low molecular weight Heparin (LMWH) whilst opposing the use of aspirin. We compared thromboembolic events, major haemorrhage and death after knee replacement in patients receiving either aspirin or LMWH. Methods. Data from the National Joint Registry for England and Wales was linked to an administrative database of hospital admissions in the English National Health Service. A total of 156 798 patients undergoing knee replacement between April 2003 and September 2008 were included and followed up for 90 days. Multivariable risk modelling was used to estimate odds ratios adjusted for baseline risk factors (AOR). An AOR < 1 indicates that risk rates are lower with LMWH than with aspirin. Results. In all, 23.1% of patients were prescribed aspirin and 76.9% LMWH. We found no statistically significant differences in the rate of pulmonary embolism (aspirin 0.49%, LMWH 0.45%, AOR 0.88; 95% confidence intervals (CI) 0.74 to 1.05), 90-day mortality (0.39% versus 0.45%, AOR 1.13; 95% CI 0.94–1.37) and major haemorrhage (0.37% versus 0.39%, AOR 1.01; 95% CI 0.83–1.22). There was a significantly greater likelihood of requirement for return to theatre in the aspirin group (0.26% versus 0.19%, AOR 0.73; 95% CI 0.58–0.94). Discussion. Between patients receiving LMWH or aspirin, there was no difference in the risk of pulmonary embolus, 90-day mortality and major haemorrhage. These results should be considered when the existing guidelines for thromboprophylaxis after knee replacement are reviewed

The purpose of the present study is to determine the incidence, location and rate of VTE following routine mechanical, chemical prophylaxis in trauma/elective patients and to understand what factors are responsible for the continuing high frequency of thromboembolic complication despite the fact that low molecular-weight heparin (LMWH) is now widely used for prophylaxis. All of the inpatients at the orthopaedics ward, Princess Alexandra Hospital (level one trauma centre, Brisbane) between the first May 2009 and 30th of April 2010 with the diagnosis of DVT/PE were included in this study. Patients were chosen based on the diagnosis of DVT with ultrasound or PE with CTPA during their admission in this period which was performed whenever clinical signs indicated DVT or PE. 64% of the included patients had DVT and 42% had PE which was developed during their admission. Included patients had a mean age ±SD age of 56years ± 23 years, 68% were men and 72% suffered trauma. The 18% of patients had previous history of PE or DVT. The incidence of VTE was significantly higher in men at ages between 20–40 .29% of the patients had ICU admission during their stay in hospital. 28%had spinal cord injury, 21%with head trauma, and 36%with multiple bone fractures. Most of the patients had lower limb injury or operation and just one patient was with isolated upper limb injury. The mean period of hospitalization for the included patients were 29 ± 19 days (range, 6–77). DVTs occurred 8 days ± 7 days(range, 1–31) post admission. PEs occurred 10 days ± 8 days (range, 3–30) after admission. Location of DVT was available for 14 patients: 9 (64%)lower and 6 (43 %)upper, with one(0.07%)having both. Twelve of 28 patients with VTE were started on prophylactic clexane (40mg once daily), and six patients were on heparin(5000 unit twice daily). All of the patients with PE had lower limb injury. Considering the number of orthopaedics ward patients during our study period our data show the incidence of VTE in one year is lower than that of literature and the common standard prophylaxis with early mechanical prophylaxis after admission and following pharmacological prophylaxis when it is safe has acceptable results

Study design: In order to evaluate a new CECT (Continuous Enhanced Circulation Therapy) based on protocol for DVT prevention a prospective, randomize, single-blind study was designed to compare the effect of the new protocol to the current standard of care in DCT prophylaxis (LMWH).

Objectives: To evaluate and compare the incidence and severity of DVT between the two groups.

Background: Total hip and knee replacements are operations particularly prone to thromboembolic complications. Recommendations regarding prophylaxis have changed over the years. A treatment protocol was proposed, based upon the CECT system as the primary DVT prophylaxis method with the addition of low dose aspirin. This protocol is using two very safe treatment modalities with very low risk for adverse effects. The CECT system applies continuous mechanical enhancement of venous blood flow through a miniature, mobile, battery operated system.

Methods: 39 patients, who underwent total hip or knee replacement, were prospectively randomized into two groups. In the study group the patients received CECT system starting immediately after the induction of anesthesia and covering the operation and the first 5 postoperative days, within 12 hours after surgery aspirin 100 mg per day was added. In the control group the patients received Enoxaparin 40 mg per day for 5 postoperative days. A venography was performed at the 5th to 8th post-operative day and the DVT prevalence was compared.

Results: In the study group 3 patients out of 21 (14.3%) were found to have DVT (1 of them proximal), compared to 8 patients out of 18 (44.4%) in the control group (5 of them proximal). The differences between the two groups are statistically significant for both total and proximal DVT rates (p=0.037).

In the study group only 1 patient needed prolonged high dose anticoagulant treatment while 6 patients in the enoxaparin group were treated (p=0.020).

The cumulative incidence of adverse events in the study group was significantly lower than that observed in the control group (p=0.000). Average postoperative hospital stay was 8.4 days in the study group and 11.7 days in the control group (p=0.002).

The CECT device was very well tolerated by the patients and facilitated early mobilization.

Conclusions: The protocol combining CECT and Aspirin was found to be both safe the effective. Comparison to the standard prophylaxis with enoxaparin revealed significant advantage of the proposed protocol with: better DVT prevention, less adverse events and shorter hospital stay. Further research is needed in order to establish the place of this prophylaxis protocol as the treatment of choice in orthopaedic patients.

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

The regenerative potential of bone grafts is tightly linked to the interaction of the biomaterial with the host tissue environment. Hence, strategies to confer artificial extracellular matrix (aECM) cues on the material surface are becoming a powerful tool to trigger the healing cascade and to stimulate bone regeneration. The use of glycosaminoglycans (GAGs), such as heparin, as aECM components has gained interest in the last years as a strategy to improve biological response. Calcium phosphates (CaP) are extensively used as bone grafts, however no studies have investigated the effect of GAG functionalisation on their surface. Some authors have focused on the effects of GAGs on osteoblastic cells, however, little work has been performed on the interaction with osteoclasts (OC), and still the reported effects are controversial [1]. The aim of this study was to investigate the effect of heparin on osteoclastic fate in terms of adhesion and differentiation. Sintered CaP (β-TCP) and biomimetic CaP (calcium-deficient hydroxyapatite, CDHA) discs were synthesized at 1100 ºC and at 37ºC, respectively. Heparinisation was achieved though silane coupling (APTES) followed by amidation in the presence of EDC/NHS to covalently link heparin. The osteoclast response of heparinised (H) vsnon-heparinised substrates was studied using human monocytes as OC precursors. Tissue culture plastic (TCPS) was used as a control sample. Cell densities were 6·10. 6. and 3·10. 6. cells/cm. 2. for biomaterials and TCPS, respectively. Cell cultures were supplemented every 3 days with 25% supernatant of osteoblast-like cell line as a source of RANKL, as well as other stimulating factors [2]. Tartrate-resistant acid phosphatase and Hoechst staining were used to evaluate OC adhesion, differentiation and morphology at different time points from seeding on the surfaces (14–21–28 days). OC precursors showed adhesion on all substrates. β-TCP and β-TCP-H hosted higher number of OC precursors which might be related to the smoother sintered surface of the materials. Oppositely, the high roughness of CDHA and CDHA-H hamper the adhesion of OC, hence a lower number of cells was observed on heparin-coated and uncoated biomimetic apatites. However, the maturation of OC precursors was found to take place at earlier times (14days) on biomimetic substrates compared to sintered ones. TCPS, CDHA, CDHA-H and β-TCP-H showed clearly differentiated OC at 14 days, as revealed by TRAP positivity and multinuclearity. Interestingly, CDHA-H and β-TCP-H induced the highest multinuclearity among all differentiated OC. Both heparinised substrates point at an enhancing effect of heparin on OC maturation. OC precursors are able to differentiate on β-TCP and CDHA substrates, a process enhanced when heparin functionalisation is performed on the materials surface. In our hands heparinisation is promoting OC differentiation at early time points, similarly to TCPS control. Interestingly, heparin substrates induced larger TRAP positive-OC and higher multinuclearity in the mature OC than TCPS control. As pointed out by Irie et al., heparin might interact through the RANKL/OPG ratio [3], thus inhibiting OPG activity and enhancing RANKL which triggers OC maturation

Total Joint Arthroplasty (TJA) is a successful orthopaedic procedure allowing dramatic clinical and functional improvements. Globally, there's been an increase in demand and performed cases associated with an increase in complications. Subsequently, focus on the prevention of complications has become important worldwide. The incidence of venous-thrombolic events (VTE) despite great attention has not diminished despite much investigation. A balance between efficacy and safety from the available agents is essential. Low molecular weight heparin (LMWH) has been commonly used, but oral anti-coagulants have become more popular. The aim of this study was to assess the adherence LMWH and the effectiveness and safety of preventing VTE in post-operative arthroplasty patients in a South African setting. We conducted a prospective cohort study that included hip and knee, primary and revision, arthroplasty patients who received thromboprophylaxis with one daily injection of LMWH for 14 days post discharge. Patients who omitted 1 or more doses during the follow up period were classified as “non adherent”. A questionnaire was used at follow up visits at least 6 weeks post-operatively. 100 consecutive patients were followed up. The mean age of patients was 63.45 years. There were 68 % female patients. There was a 92% compliance rate. 60 % of patients had the injection administered by a family member, 38 % administered it themselves and 2 % had the injection administered by health professionals. Venous thromboembolic events were confirmed in 5 % at 7.86 days after surgery. Three patients had persistent wound drainage after surgery, however, none required reoperation or readmission. Compliance with LMWH is high and is comparable with oral agents. It is effective in preventing VTE and safe with regards to bleeding and wound complications in a South African setting. Patient education regarding medications may improve compliance of the medication

Cell-based tissue engineering is a promising approach for treating cartilage lesions but the optimal cell-scaffold combination for hyaline cartilage regeneration has yet to be identified. Novel hydrogels allow including tailored tissue type specific modifications with physiologically relevant peptides, by this selectively influencing the cell response. Aim of this study was to modify a poly(ethylene glycol) (PEG)/heparin hydrogel by functionalization with cell instructive peptides introducing matrix-metalloprotease (MMP)-degradability, the cell adhesion motif RGD, or collagen binding motifs (CKLER, CWYRGRL) to improve cartilage matrix deposition in tissue engineering constructs. The hydrogels were formed by mixing thiol-endfunctionalized (MMP-insensitive) starPEG or starPEG-MMP-conjugates carrying MMP-sensitive peptides at every arm and maleimide-functionalized heparin [1] in the presence or absence of cell instructive peptides. Human mesenchymal stromal cells (MSC) or porcine chondrocytes were grown in the hydrogels for up to 4 weeks in vitro under chondrogenic conditions, and in vivo in subcutaneous pockets of immunodeficient mice. MMP-sensitive and –insensitive starPEG/heparin hydrogels supported chondrogenic differentiation of MSC according to induction of COL2A1, BGN and ACAN mRNA expression. Enhanced MMP-sensitivity and therefore degradability increased cell viability and proliferation. RGD-modification of the hydrogels induced cell-spreading and an intensively interconnected cell network. Other than hypothesized, CKLER and CWYRGRL were unable to raise collagen deposition in constructs in vitro. Matrix deposition in chondrocyte-containing peptide-functionalized hydrogels was high and the instructive effect of the hydrogels on chondrocytes appeared stronger in vivo where the merely pericellular cartilaginous matrix deposition was overcome in RGD-functionalized starPEG/heparin hydrogels. Peptide-functionalized starPEG/heparin hydrogel altered cell morphology, proliferation and differentiation with MSC being similar sensitive to cell-matrix interaction peptides like articular chondrocytes. We also demonstrated that in vivoperformance of cell instructive hydrogels can exceed results gained by in vitromodels. Altogether, the manipulation of hydrogel constructs with signaling cues is considered promising for functional cartilage tissue engineering

Thrombelastography (TEG) is a point-of-care tool that can measure clot formation and breakdown using a whole blood sample. We have previously used serial TEG analysis to define hypercoagulability and increased venous thromboembolism (VTE) risk following a major fracture requiring surgical treatment. Additionally, we have used serial TEG analysis to quantify the prolonged hypercoagulable state and increased VTE risk that ensues following a hip fracture. Recently developed cartridge-based platelet mapping (PLM) using TEG analysis can be used to activate platelets at either the adenosine diphosphate (ADP) receptor or at the Thromboxane A2 (AA) receptor, in order to evaluate clot strength when platelets are activated only through those specific receptors. This study aim was to evaluate platelet contribution to hypercoagulability, in order to identify potential therapeutic targets for VTE prevention. We hypothesized that there would be a platelet-predominant contribution to hypercoagulability following a hip fracture. Patients aged 50 years or older with a hip fracture treated surgically were enrolled in this prospective cohort study. Exclusion criteria were: prior history of VTE, active malignancy, or pre-injury therapeutic dose anticoagulation. Serial TEG and PLM analyses were performed at admission, post-operative day (POD) 1, 3, 5, 7 and at 2-, 4-, 6- and 12-weeks post-operatively. All patients received thromboprophylaxis with low molecular weight heparin (LMWH) for 28 days post-operatively. Hypercoagulability was defined as maximal amplitude (MA; a measure of clot strength) over 65mm based on TEG analysis. Independent samples t-tests were used to compare MA values with this previously established threshold and a mixed effects linear regression model was used to compare MA values over time. Independent samples t-tests and Chi-sqaured analyses were used to compare between the surgical fixation and arthroplasty groups. Forty-six patients with an acute hip fracture were included, with a mean age of 77.1 (SD = 10.6) years, with 61% (N=11) being female. Twenty-six were treated with arthroplasty (56.5%), while the remainder underwent surgical fixation of their hip fractures. TEG analysis demonstrated post-operative hypercoagulability (mean MA over 65mm) at all follow-up timepoints until 12-weeks. PLM identified a platelet-mediated hypercoagulable state based on elevated ADP-MA and AA-MA, with more pronounced platelet contribution demonstrated by the AA pathway. Patients treated with arthroplasty had significantly increased AA-MA compared with ADP-MA at POD 3 and at the 12-week follow-up. Thrombelastography can be used to identify hypercoagulability and increased risk for VTE following a hip fracture. Platelet mapping analysis from this pilot study suggests a platelet-mediated hypercoagulable state that may benefit from thromboprophylaxis using an anti-platelet agent that specifically targets the AA platelet activation pathway, such as acetylsalicylic acid (ASA). This research also supports differences in hypercoagulability between patients treated with arthroplasty compared to those who undergo fracture fixation