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’

The administration of heparin during operation has been reported to enhance the efficacy of thromboprophylaxis in patients undergoing total hip replacement. We have performed a small pilot study in which intraoperative doses of heparin were given in addition to the usual postoperative thromboprophylaxis with enoxaparin in 32 patients undergoing total knee replacement. The primary endpoint was deep-vein thrombosis (DVT) as demonstrated by bilateral venography on 6 ± 2 days after operation. Sixteen patients developed DVT; in two the thrombosis was proximal as well as distal and in one the occurrence was bilateral. There was one major haemorrhage. These results are similar to those obtained with the use of postoperative thromboprophylaxis with enoxaparin alone. They do not provide support for the initiation of a larger randomised trial of this approach to management

Aims. We investigated the efficacy and safety profile of commonly used venous thromboembolism (VTE) prophylaxis agents following hip and knee arthroplasty. Methods. A systematic search of PubMed, Embase, Cochrane Library, Web of Science, and OrthoSearch was performed. Prophylaxis agents investigated were aspirin (< 325 mg and ≥ 325 mg daily), enoxaparin, dalteparin, fondaparinux, unfractionated heparin, warfarin, rivaroxaban, apixaban, and dabigatran. The primary efficacy outcome of interest was the risk of VTE, whereas the primary safety outcomes of interest were the risk of major bleeding events (MBE) and wound complications (WC). VTE was defined as the confirmed diagnosis of any deep vein thrombosis and/or pulmonary embolism. Network meta-analysis combining direct and indirect evidence was performed. Cluster rank analysis using the surface under cumulative ranking (SUCRA) was applied to compare each intervention group, weighing safety and efficacy outcomes. Results. Of 86 studies eligible studies, cluster rank analysis showed that aspirin < 325 mg daily (SUCRA-VTE 89.3%; SUCRA-MBE 75.3%; SUCRA-WC 71.1%), enoxaparin (SUCRA-VTE 55.7%; SUCRA-MBE 49.8%; SUCRA-WC 45.2%), and dabigatran (SUCRA-VTE 44.9%; SUCRA-MBE 52.0%; SUCRA-WC 41.9%) have an overall satisfactory efficacy and safety profile. Conclusion. We recommend the use of either aspirin < 325 mg daily, enoxaparin, or dabigatran for VTE prophylaxis following hip and knee arthroplasty. Cite this article: Bone Joint J 2024;106-B(9):924–934

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

Thrombin has many biological properties similar to those of growth factors. In a previous study, we showed that thrombin improves healing of the rat tendo Achillis. Low molecular weight heparin (LMWH) inhibits the activity and the generation of thrombin. We therefore considered that LMWH at a thromboprophylactic dose might inhibit tendon repair. Transection of the tendo Achillis was carried out in 86 rats and the healing tested mechanically. Low molecular weight heparin (dalateparin) was either injected a few minutes before the operation and then given continuously with an osmotic mini pump for seven days, or given as one injection before the operation. In another experiment ,we gave LMWH or a placebo by injection twice daily. The anti-factor Xa activity was analysed. Continuous treatment with LMWH impaired tendon healing. After seven days, this treatment caused a 33% reduction in force at failure, a 20% reduction in stiffness and a 67% reduction in energy uptake. However, if injected twice daily, LMWH had no effect on tendon healing. Anti-factor Xa activity was increased by LMWH treatment, but was normal between intermittent injections. Low molecular weight heparin delays tendon repair if given continuously, but not if injected intermittently, probably because the anti-factor Xa activity between injections returns to normal, allowing sufficient thrombin stimulation for repair. These findings indicate the need for caution in the assessment of long-acting thrombin and factor Xa inhibitors

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

1. Reports of the lipaemia-clearing effect of heparin suggested that this drug might be of therapeutic value in fat embolism. 2. In an experimental trial with rats, heparin was found both to accelerate death and to increase the number of deaths after fat embolism. 3. It is accordingly concluded that a clinical trial of heparin in human fat embolism would not be warranted

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

We performed a randomised controlled study to compare heparin with the A-V Impulse System in the prevention of deep-vein thrombosis (DVT) in 132 consecutive patients undergoing total hip replacement. After the operation, all patients had compression stockings, 65 were treated with calcium heparin and 67 with the intermittent plantar pump. DVT was diagnosed by Doppler ultrasound and thermography, followed by phlebography. There were 23 cases of DVT (35.4%) in the heparin group, with 16 major and seven minor thromboses. In the impulse pump group there were nine cases (13.4%) with three major and six minor thromboses. The differences for all thromboses and for major thromboses were both significant at p < 0.005. In the heparin group there was one fatal pulmonary embolism and nine patients (13.8%) had excessive bleeding or wound haematomas, as against none in the impulse pump group

We studied the safety of combining the postoperative use of a non-steroidal anti-inflammatory drug with low-dose heparin. In a double-blind, placebo-controlled clinical trial we reviewed the complications in 235 patients after total hip replacement, all treated with low-dose heparin and either indomethacin or a placebo. The incidence and type of complications in the two groups were nearly equal; indomethacin-treated patients had no increase in complications related to bleeding. Postoperative bleeding into drains was marginally greater in the indomethacin group, although the difference was not statistically significant. We conclude that treatment with indomethacin and low-dose heparin after hip replacement does not significantly increase the bleeding or other complications. We also found that patients receiving indomethacin were mobilised an average of one day before those on placebo

A prospective study involving 500 consecutive patients undergoing hip replacement was performed to find out whether a combination of heparin and dihydroergotamine was effective in preventing postoperative fatal and non-fatal emboli. Deep-vein thrombosis was demonstrated in 131 cases (26.2%), in 99 of whom thrombi were confined to the ipsilateral (operated) limb and in 13 to the contralateral limb; 19 patients developed bilateral thrombi. Nine patients (1.8%) died during the first four weeks after operation, before they were discharged from hospital; in one, major emboli were demonstrated in the right pulmonary artery. Three of the 500 patients developed non-fatal pulmonary emboli. Excessive bleeding occurred in 21 (4.2%) and in 19 of these prophylaxis was discontinued. Wound haematomas developed in 25 patients (5.0%); only six required evacuation but in none of these six did deep infection occur while in hospital; in three patients, however, the wound haematoma prolonged the stay in hospital. Thus the combination of heparin and dihydroergotamine proved an effective prophylaxis against pulmonary embolism in patients undergoing total hip replacement. The risk of bleeding complications is wholly acceptable when balanced against the advantages of the therapy

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

In a double-blind, randomised study of thromboprophylaxis in patients undergoing total hip replacement, we compared a low-molecular-weight heparin with a placebo. Of the 120 patients enrolled, 112 completed the trial; 58 in the treatment group and 54 in the placebo group. Nine (16%) patients in the treatment group and 19 (35%) in the placebo group developed deep venous thrombosis, diagnosed by the 125I-fibrinogen uptake test (p < 0.02). Verification was obtained by phlebography in 86% of the patients. Prolonged surgery increased the risk of thrombosis in the placebo group but not in the treatment group (p < 0.05). There were significantly more cases of deep venous thrombosis in the placebo group during the first four postoperative days (p < 0.02). The groups did not differ with respect to peroperative and postoperative bleeding. Low-molecular-weight heparin offers safe and easily administered thromboprophylaxis in total hip replacement

The optimal method of prophylaxis against venous thromboembolism after total hip replacement (THR) remains uncertain. Most surgeons use some form of pharmacological prophylaxis, most commonly heparin. The precise balance of the benefits and risks is unclear, and serious complications can occur. We describe a case of heparin-induced thrombocytopenia and thrombosis syndrome in a 62-year-old woman after THR

In a randomised trial we compared the effects of two different antithrombotic regimens on the incidence of venographically established deep venous thrombosis (DVT) in 83 patients undergoing surgery for fracture of the femoral neck. Group A received dextran 40 peroperatively plus 0.5 g aspirin a day beginning before operation and continuing for 10 days after. Group B received heparin calcium 5000 iu subcutaneously plus dihydroergotamine (DHE) 0.5 mg intramuscularly, given 8-hourly, beginning before operation and continuing for 10 days after. Two patients in Group A and three in Group B developed proximal DVT, while the incidence of all DVT was 33% in Group A and 29% in Group B, a difference which was not significant. Haemorrhagic complications were much more common in the dextran/aspirin group: the volume of drainage fluid, the number of patients transfused and quantity of blood transfused, and the drop in haemoglobin level were all significantly greater in Group A. We conclude that the DHE/heparin regime is preferable to dextran/aspirin because it is safer and no less effective

In previous randomised clinical trials of thromboprophylaxis after total hip replacement, low-molecular-weight heparin has been given for an arbitrary 7 to 14 days. The risk factors are mainly perioperative and it is possible that a shorter course may be adequate. We assessed the safety and effectiveness of a three-day course. We assessed 156 primary THR patients after randomisation to either a control group or to receive enoxaparin at 12 hours preoperatively and 12 and 36 hours postoperatively. Thrombosis was diagnosed by routine venography. Haemorrhagic side-effects were assessed by measurement of blood loss, and soft-tissue side-effects by descriptive scores for wound discharge and bruising of the leg. The prevalence of calf thrombosis was 15.4% in the enoxaparin group and 32.1% in the control group (p = 0.01); the prevalence of proximal thrombosis was 15.4% and 17.9% respectively (not significant). There was no difference in haemorrhagic side-effects or wound discharge, but there was more bruising in the enoxaparin group

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

Patients who undergo total knee replacement (TKR)are at high risk of venous thromboembolism. Low-molecular-weight heparins (LMWH) are the most suitable chemical prophylactic agents but there are some uncertainties about their safety and effectiveness. The foot pump offers an alternative. We randomised 229 patients undergoing primary, unilateral TKR to receive either the A-V Impulse foot pump or enoxaparin, a LMWH. Ascending venography was undertaken between the sixth and eighth postoperative day in 188 patients without knowledge of the randomisation category. The prevalence of venographic deep-vein thrombosis was 58% (57/99) in the foot-pump group and 54% (48/89) in the LMWH group which was not statistically significant. There were four cases of proximal thrombi and two of fatal pulmonary emboli in the foot-pump group and none in the LMWH group. There were fewer haemorrhagic complications and soft-tissue effects in the foot-pump group. We conclude that the neither method provides superior prophylaxis

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

Enoxaparin, a low-molecular-weight heparin, has been used together with spinal or general anaesthesia in a prospective, randomised study of 188 consecutive elective hip replacements. Bilateral venography was performed on all patients on day 13 after operation. Group I (65 patients) received spinal anaesthesia and no immediate injection of enoxaparin. Group II (61 patients) received spinal anaesthesia and 20 mg of enoxaparin one hour after the onset of anaesthesia. Group III (62 patients) was operated on under general anaesthesia and received 40 mg of enoxaparin 12 hours prior to surgery. This group acted as the control group. In all three groups, 40 mg of enoxaparin was given 12 hours after the end of surgery and continued on a once-daily basis. Proximal DVT occurred in 6% of group I, 6.7% of group II and 6.5% of group III, not a significant difference. Distal DVT was present in 11% of group I, 5% of group II and 0% of group III; this was a highly significant difference (p = 0.007). Tolerance was good and the incidence of bleeding low in the three groups. Our results confirm the low rate of DVT in patients operated on under general anaesthesia with the standard procedure of 40 mg of enoxaparin on a once-daily basis started pre-operatively. The 40 mg-dose is also safe and effective in association with spinal anaesthesia if half the dose (20 mg) is injected an hour after the lumbar puncture

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.

The June 2023 Trauma Roundup. 360. looks at: Aspirin or low-molecular-weight heparin for thromboprophylaxis?; Lateral plating or retrograde nailing for distal femur fractures?; Sciatic nerve palsy after acetabular fixation: what about patient position?; How reliable is the new OTA/AO classification for trochanteric hip fractures?; Young hip fractures: is a medial buttress the answer?; When is the best time to ‘flap’ an open fracture?; The mortality burden of nonoperatively managed hip fractures

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

Major orthopaedic fractures are an independent risk factor for the development of venous thromboembolism (VTE), which are significant causes of preventable morbidity and mortality in trauma patients. Despite thromboprophylaxis, patients who sustain a pelvic or acetabular fracture (PA) continue to have high rates of VTE (12% incidence). Thrombelastography (TEG) is a whole-blood, point-of-care test which provides an overview of the clotting process. Maximal amplitude (MA), from TEG analysis, is the measure of clot strength and values ≥65mm have been used to quantify hypercoagulability and increased VTE risk. Therefore, the primary aim was to use serial TEG analysis to quantify the duration of hypercoagulability, following surgically treated PA fractures. This is a single centre, prospective cohort study of adult patients 18 years or older with surgically treated PA fractures. Consecutive patients were enrolled from a Level I trauma centre and blood draws were taken over a 3-month follow-up period for serial TEG analysis. Hypercoagulability was defined as MA ≥65mm. Exclusion criteria: bleeding disorders, active malignancy, current therapeutic anticoagulation, burns (>20% of body surface) and currently, or expecting to become pregnant within study timeframe. Serial TEG analysis was performed using a TEG6s hemostasis analyzer (Haemonetics Corp.) upon admission, pre-operatively, on post-operative day (POD) 1, 3, 5, 7 (or until discharged from hospital, whichever comes sooner), then in follow-up at 2-, 4-, 6-weeks and 3-months post-operatively. Patients received standardized thromboprophylaxis with low molecular weight heparin for 28 days post-operatively. VTE was defined as symptomatic DVT or PE, or asymptomatic proximal DVT, and all participants underwent a screening post-operative lower extremity Doppler ultrasound on POD3. Descriptive statistics were used to determine the association between VTE events and MA values. For the primary outcome measure, the difference between the MA threshold value (≥65mm) and serial MA measures, were compared using one-sided t-tests (α=0.05). Twenty-eight patients (eight females, 29%) with a mean age of 48±18 years were included. Acetabular fractures were sustained by 13 patients (46%), pelvic fractures by 14 patients (50%), and one patient sustained both. On POD1, seven patients (25%) were hypercoagulable, with 21 patients (78%) being hypercoagulable by POD3, and 17 patients (85%) by POD5. The highest average MA values (71.7±3.9mm) occurred on POD7, where eight patients (89%) were hypercoagulable. At 2-weeks post-operatively, 16 patients (94%) were hypercoagulable, and at four weeks, when thromboprophylaxis was discontinued, six patients (40%) remained hypercoagulable. Hypercoagulability persisted for five patients (25%) at 6-weeks and for two patients (10%) by three months. There were six objectively diagnosed VTE events (21.4%), five were symptomatic, with a mean MA value of 69.3mm±4.3mm at the time of diagnosis. Of the VTE events, four occurred in participants with acetabular fractures (three male, 75%) and two in those with pelvic fractures (both males). At 4-weeks post-operatively, when thromboprophylaxis is discontinued, 40% of patients remained hypercoagulable and likely at increased risk for VTE. At 3-months post-operatively, 10% of the cohort continued to be hypercoagulable. Serial TEG analysis warrants further study to help predict VTE risk and to inform clinical recommendations following PA fractures

The incidence of deep-vein thrombosis and the need for thromboprophylaxis following isolated trauma below the knee is uncertain. We have investigated this with a prospective randomised double-blind controlled trial using low molecular weight heparin with saline injection as placebo in patients aged between 18 and 75 years who had sustained an isolated fracture below the knee which required operative fixation. All patients had surgery within 48 hours of injury and were randomised to receive either the placebo or low molecular weight heparin for 14 days, after which they underwent bilateral lower limb venography, interpreted by three independent radiologists. Further follow-up was undertaken at two, six, eight and 12 weeks. A total of 238 patients fulfilled all the inclusion criteria, with 127 in the low molecular weight heparin group and 111 in the placebo group, all of whom underwent bilateral venography. There was no statistically significant difference in the incidence of deep-vein thrombosis between those patients treated with low molecular weight heparin or the placebo (p = 0.22). The number of deep-vein thromboses in the two groups was 11 (8.7%) and 14 (12.6%), respectively. Age and the type of fracture were significantly associated with the rate of deep-vein thrombosis (p = 0.001 and p = 0.009, respectively) but gender, comorbidities and the body mass index were not. The overall incidence of deep-vein thrombosis in this series was 11%. There was no clinical or statistical significant reduction in the incidence of deep-vein thrombosis with the use of thromboprophylaxis. However, we accept that owing to a cessation of funding, recruitment to this trial had to be ended prior to establishing the necessary sample size. Our results cannot, therefore, categorically exclude the possibility that low molecular weight heparin treatment could be beneficial. We recommend a further multicentre trial be undertaken to resolve this matter

Aims. We studied the safety and efficacy of multimodal thromboprophylaxis in patients with a history of venous thromboembolism (VTE) who undergo total hip arthroplasty (THA) within the first 120 postoperative days, and the mortality during the first year. Multimodal prophylaxis includes discontinuation of procoagulant medications, VTE risk stratification, regional anaesthesia, an intravenous bolus of unfractionated heparin prior to femoral preparation, rapid mobilization, the use of pneumatic compression devices, and chemoprophylaxis tailored to the patient’s risk of VTE. Methods. Between 2004 to 2018, 257 patients with a proven history of VTE underwent 277 primary elective THA procedures by two surgeons at a single institution. The patients had a history of deep vein thrombosis (DVT) (186, 67%), pulmonary embolism (PE) (43, 15.5%), or both (48, 17.5%). Chemoprophylaxis included aspirin (38 patients), anticoagulation (215 patients), or a combination of aspirin and anticoagulation (24 patients). A total of 50 patients (18%) had a vena cava filter in situ at the time of surgery. Patients were followed for 120 days to record complications, and for one year to record mortality. Results. Postoperative VTE was diagnosed in seven patients (2.5%): DVT in five, and PE with and without DVT in one patient each. After hospitalization, three patients required readmiss-ion for evacuation of a haematoma, one for wound drainage, and one for monitoring of an elevated international normalized ratio (INR). Seven patients died (2.5%). One patient died five months postoperatively of a PE during open thrombectomy. She had discontinued anticoagulation. One patient died of a haemorrhagic stroke while receiving Coumadin. PE or bleeding was not suspected in the remaining five fatalities. Conclusion. Multimodal prophylaxis is safe and effective in patients with a history of VTE. Postoperative anticoagulation should be prudent as very few patients developed VTE (2.5%) or died of suspected or confirmed PE. Mortality during the first year was mostly unrelated to either VTE or bleeding. Cite this article: Bone Joint J 2020;102-B(7 Supple B):71–77

Introduction. We studied the safety and efficacy of multimodal thromboprophylaxis (MMP) in patients with a history of venous thromboembolism (VTE) undergoing total hip arthroplasty (THA). MMP includes discontinuation of procoagulant medications, VTE risk stratification, regional anesthesia, an intravenous bolus of unfractionated heparin before femoral work, rapid mobilization, the use of pneumatic compression devices, and chemoprophylaxis tailored to the patient's risk. Material and methods. From 2004 to 2018, 257 patients (mean age: 67 years; range: 26–95) with a history of VTE underwent 277 primary, elective THAs procedures (128 right, 100 left, 9 single-stage bilateral, 20 staged bilateral) by two orthopaedic surgeons at a single institution. The patients had a history deep vein thrombosis (DVT) 186 (67%), pulmonary embolism (PE) 43 (15.5%), or both 48 (17.5%). Chemoprophylaxis included aspirin (38 patients) and anticoagulation (239 patients; Coumadin: 182, low-molecular-weight heparin: 3, clopidogrel: 1, rivaroxaban: 3, and a combination: 50). Forty eight patients (17.3%) had a vena cava filter at the time of surgery. Patients were followed for 120 days to detect complications, and for a year to detect mortality. Results. Postoperative VTE was diagnosed in seven patients (2.5%): DVT in five, and PE with and without DVT in one patient each. Bleeding complications occurred in 2 patients, one requiring surgical evacuation of a hematoma. Seven patients died during the first year (2.5%). One patient died 5 months postoperatively of a fatal PE during open thrombectomy, and one patient died of a hemorrhagic stroke while receiving Coumadin. PE or bleeding was not suspected in any of the remaining 5 fatalities. Conclusions. The result of this study spanning over 13 years, suggests that MMP is safe and effective. Postoperative anticoagulation should be prudent as very few patients developed postoperative VTE (2.5%) or died of suspected or confirmed PE. Mortality during the first year was mostly unrelated to VTE or bleeding. For any tables or figures, please contact the authors directly

Introduction. Melatonin-deficient rats are known to develop scoliosis when rendered bipedal. In a previous study we have shown that melatonin-deficient bipedal mice with scoliosis had lower bone density than did mice without scoliosis. Published work suggests that children with AIS have lower bone density than do healthy children. The aim of this study is to establish whether osteoporosis causes scoliosis. We hypothesised that bipedal rats with lower bone density would have increased spinal malalignment compared with the control group. Methods. 50 female Sprague-Dawley rats were rendered bipedal at 3 weeks of age by amputation of the forelimbs and tails. Two groups were formed: control group (n=25), in which rats received no drug; and the experiment group (n=25), in which rats received daily subcutaneous 1 U/g heparin injections. Animals were kept in standard cages, and food and water was provided at the top of the cages to encourage more time standing erect. DEXA scans were done on week 4 to assess bone density. Radiographs were taken on week 40 to assess spinal alignment in both control and experiment groups. Results. 19 rats in the heparin group and 23 rats in the control group were available for evaluation at the end of the study. At week 4, DEXA scans showed significant difference between the bone densities of the control and heparin groups (p<0·05), with the heparin group having lower bone density. The incidence of curves between the heparin and control groups were not statistically significant (p>0·01) (table). The magnitude of curves in scoliotic rats for the heparin group was 11·8° (SD 3·75) and for the control group 10° (4·3). The difference between the groups was not significant (p>0·05). Conclusions. This study involved rats with normal melatonin levels and both groups showed a high frequency of scoliosis incidence. Although no significant differences were recorded between groups, the results suggest that bipedality is a cause for scoliosis, and low bone mineral density may further increase this tendency

Background. Hip fracture in the elderly has high morbidity and mortality. National guidelines have recommended low molecular weight (LMW) heparin or aspirin for thromboprophylaxis in hip fracture. Unlike other types of major surgery, there is a lack of trial evidence for graduated elasticated compression (GEC) stockings in hip fracture patients. Objective. To explore the effect of thromboprophylaxis on survival in hip fracture patients. Participants. 8470 Scottish Hip Fracture Audit (SHFA) participants aged 60 years and over, admitted 1998-2003. Methods. SHFA records were linked to routinely collected hospital discharge and death records occurring within one year of hip fracture admission. Cox proportional hazards regression was used to adjust for age, gender, previous hospital admissions, previous walking ability and residence, American Society of Anesthesiologists grade, fracture type, pressure sores prior to surgery, and delay to surgery. Results. 2531 (30%) patients died within one year of hip fracture admission. GEC stockings appeared to be protective against death (hazard ratio 0.88, 95% confidence interval 0.80-0.97) as did aspirin (HR 0.85, 95% CI 0.76-0.95). However heparin did not appear to protect against death (HR 0.97, 95% CI 0.87-1.08), even when only LMW heparin was included in the analysis. Overall, 3318 (39%) patients were given GEC stockings, 2735 (32%) aspirin, and 4527 (53%) heparin. Patients commonly received more than one type of thromboprophylaxis. Conclusions. This study provides evidence for a protective effect of GEC stockings and aspirin following hip fracture, but not heparin. The study design allowed sophisticated analysis, adjusting for a number of functional, social, surgical, anaesthetic and medical factors. The findings may however be explained by other confounding factors not included in the analysis. These findings suggest that a randomised controlled trial of GEC stockings, aspirin and heparin in hip fracture patients is warranted

Heparin is a drug widely used for thromboprophylaxis or treatment in many clinical situations. However, it can cause serious adverse effects, including thrombocytopenia, which is a potentially life-threatening condition. Unfortunately, heparin-induced thrombocytopenia is generally under-recognised and under-diagnosed. A case of heparin-induced thrombocytopenia occurring in a post-operative orthopaedic patient in association with prophylactic low-molecular-weight heparin is described

Total knee arthroplasty (TKA) is one of the most successful surgeries to relieve pain and dysfunction caused by severe arthritis of the knee. Despite developments in prophylactic methods, deep venous thrombosis (DVT) and pulmonary embolism (PE) continue to be a serious complication following TKA. Otherwise DVT/PE is known to be a relatively low incidence in Asian patients, its accurate incidence is still controversial. Therefore, we prospectively investigated the incidence of DVT/PE after primary TKA by contrast enhanced computed tomography (CE-CT) and venous ultrasonography (US) in Japanese Patients. Methods. We prospectively investigated 51 patients who underwent primary TKA at the hospital from July 2013 to December 2013. All were of Japanese ethnicity. The mean age at the surgery was 74.9 years and average BMI was 26.0. There were 45 (88.2%) cases of osteoarthritis and 5 (9.8%) of rheumatoid arthritis. A single knee surgery team performed all operations with cemented type prostheses by utilizing pneumatic tourniquet. There were 21 cases of one-staged bilateral TKA and 30 of unilateral TKA. All patients were applied intermittent pneumatic compression (IPC) until 24 hours and graduated compression stockings for 3[高木1] weeks after the operation. Beginning from the day after the surgery, the patients were allowed walking with walker, along with the gradual range of motion exercise for physical thromboprophylaxis. Low-dose unfractionated heparin (LDUH) as a chemical thromboprophylaxis was administered subcutaneously for 3 days after the surgery. Informed consent was obtained regarding this thromboprophylaxis protocol. CE-CT and venous US were performed at the 4th day after surgery and images were read by a single senior radiologist team. The patients without DVT/PE by examination, they did not take additional chemical thromboprophylaxis. In cases of existence of DVT, continuous heparin administration and oral warfarin were applied and adjusted in appropriate dose for treatment. Warfarin was continued to be applied for at least three months until the patients had no symptoms and normal D-dimer level. In cases of PE, additional ultrasonic echocardiography (UCG) was performed, and then we consulted cardiologist to treat for PE. Results. CE-CT was performed in 42 patients (82.3%), otherwise nine patients (17.7%) could not take the examination because of exclusion criteria. There was no side-effect regard to contrast medium. The incidence of DVT and/or PE was 32 patients (62.7%), including two PE (3.9%), 21 DVT (41.1%) and nine both PE and DVT (17.6%). Six-teen patients were used LDUH routinely for 3 days after surgery. Five patients were used continuous heparin administration and oral warfarin instead of using LDUH because of medical co-morbidities. Additional continuous heparin administration and oral warfarin after LDUH use was needed in 26 patients. Three patients who had duodenal ulcer with chronic pancreatitis, massive PE with right heart strain and multiple DVT/PE with HIT antibody were needed another treatment. Conclusion. We prospectively investigated 51 patients for DVT/PE after primary TKA using CE-CT and venous US. The incidence of DVT/PE after primary TKA was 62.7%, including 21.5% of PE, as high frequency in Japanese patients

Introduction. The use of intramedullary lengthening devices is becoming increasingly popular. There are no published data regarding the incidence of venous thromboembolism following intramedullary lengthening and no reports or guidance for current practices on use of thromboprophylaxis. Following a case of post-operative deep vein thrombosis in our institution, we felt that it is important to assess best practice. We conducted this survey to collect data that would describe current practice and help guide consensus for treatment. Materials and Methods. We have identified surgeons across the UK that perform intramedullary lengthening through the British Limb Reconstruction Society membership and a Precise Users database. Surgeons were contacted and asked to respond to an online survey (SurveyMonkey - SVMK Inc.). Responses to thromboprophylaxis regimes employed in their practice and cases of venous thromboembolism were collated. Results. 24 out of 54 surgeons identified responded with a total of 454 cases of intramedullary lengthening (352 femoral and 102 tibial nails) performed over the last 5 years. Only one case of DVT following femoral lengthening was reported. There is wide variability in practice both in terms of thromboprophylaxis risk assessment, choice of medications (20% no pharmacological treatment, 75% Low molecular Weight Heparin, 5% Aspirin) and duration of treatment (0–42 days). The vast majority of surgeons (85%) felt that there was insufficient evidence available to guide their practice. Conclusions. Intramedullary lengthening is a relatively recent and novel surgical treatment. As a result there is limited data available to guide decision making regarding aspects of treatment such as thromboprophylaxis. This is reflected in the wide variation in practice reported in this study. There is both a need and a desire to gather data that will allow us to come to a consensus and to guide safe practice

Considerable debate exists regarding which agent(s) should be preferred for venous thromboembolism (VTE) chemical prophylaxis following joint replacement. We assessed the practice of surgeons regarding VTE chemical prophylaxis for primary THR and TKR, pre and post issuing of updated NICE guidance in 2018. A survey, circulated through the British Hip Society and regional trainee networks/collaboratives, was completed by 306 UK surgeons at 187 units. VTE chemical prophylaxis prescribing patterns for surgeons carrying out primary THR (n=258) and TKR (n=253) in low-risk patients were assessed post publication of 2018 NICE recommendations. Prescribing patterns before and after the NICE publication were subsequently explored. Questions were also asked about surgeon equipoise for participation in future RCTs. Following the new guidance, 34% (n=87) used low-molecular weight heparin (LMWH) alone, 33% (n=85) aspirin (commonly preceded by LMWH), and 31% (n=81) direct oral anticoagulants (DOACs: with/without preceding LMWH) for THR. For TKR, 42% (n=105) used aspirin (usually monotherapy), 31% (n=78) LMWH alone, and 27% (n=68) DOAC (with/without preceding LMWH). NICE guidance changed the practice of 34% of hip and 41% of knee surgeons, with significantly increased use of aspirin preceded by LMWH for THR (before=25% vs. after=73%;p<0.001), and aspirin for TKR (before=18% vs. after=84%;p<0.001). Significantly more regimens were NICE guidance compliant after the 2018 update for THR (before=85.7% vs. after=92.6%;p=0.011) and TKR (before=87.0% vs. after=98.8%;p<0.001). Support from surgeons for future RCTs was dependent on the clinical question, ranging from 48% participation in trials (effectiveness of aspirin vs. a DOAC) to 79% (effectiveness of 14 days LMWH vs. 28 days LMWH). Over one-third of surveyed surgeons changed their VTE chemical prophylaxis in response to 2018 NICE recommendations, with more THR and TKR surgeons now compliant with latest NICE guidance. The major change in practice was an increased use of aspirin for VTE chemical prophylaxis. Furthermore, there is an appetite amongst UK surgeons for participating in future RCTs, with a trial comparing standard versus extended duration LMWH likely feasible in current practice

The aim of this study was to identify the incidence of post-operative symptomatic deep-vein thrombosis (DVT), as well as the risk factors for and location of DVT, in 665 patients (701 ankles) who underwent primary total ankle replacement. All patients received low-molecular-weight heparin prophylaxis. A total of 26 patients (3.9%, 26 ankles) had a symptomatic DVT, diagnosed by experienced radiologists using colour Doppler ultrasound. Most thrombi (22 patients, 84.6%) were localised distally in the operated limb. Using a logistic multiple regression model we identified obesity, a previous venous thromboembolic event and the absence of full post-operative weight-bearing as independent risk factors for developing a symptomatic DVT. The incidence of symptomatic DVT after total ankle replacement and use of low-molecular-weight heparin is comparable with that in patients undergoing total knee or hip replacement

Bleeding related wound complications including deep infection, superficial infection and haematoma cause significant morbidity in lower limb joint arthroplasty surgery. It has been observed anecdotally that patients requiring therapeutic anti-coagulation within the peri-operative period have higher rates of bleeding related complications and those requiring intravenous heparin particularly appear to do poorly. The aim of this study is to investigate the relationship between post-operative bleeding and wound complications in the patient requiring therapeutic warfarin, plus or minus heparin, in total hip arthroplasty surgery. This is a retrospective cohort study reviewing 1047 primary total hip replacements performed in a single centre over a five year period and comparing outcomes of the patients on warfarin (89) with a double-matched control group of patients not on warfarin (179). Outcomes included rates of deep infection, excessive wound ooze or haematoma, superficial infection, return to OT for washout and need for revision operation. The study group was then sub analysed comparing those on IV heparin plus oral warfarin, to those on warfarin alone. The warfarin group had significantly higher risk of deep joint infection (9% vs 2.2% p= 0.023), haematoma/wound ooze (28% vs 4% p < 0.001) and superficial infection (13.5% vs 2.2% p < 0.001) compared to the control group. In the sub analysis of the study group, those on IV heparin had significantly higher risk of haematoma/wound ooze (44% vs 28% p= 0.023) than those on warfarin alone. The requirement of therapeutic anti-coagulation in the peri-operative period is a tenuous balance between the complications of thrombo-embolic disease and bleeding-related morbidity. In the past, perhaps the full burden of bleeding related complications has not been appreciated, but now improved understanding will enable the both the surgeon and the patient to make more informed decisions regarding therapeutic anticoagulation in elective arthroplasty surgery

Background: The next generation of biomaterial surfaces for use in orthopaedic surgery will be functionalised to promote osteogenesis. This will be achieved in part by the stable addition of functional bioactive molecules onto the biomaterial surface. Heparan sulphate is a complex glycosaminoglycan (GAG) that displays cell and tissue specific differences in size and levels of sulphation. It is this heterogeneity that underlies the numerous biological roles of heparan sulphate, including binding of growth factors and proteases. Findings by others have shown that the addition of heparan sulphate proteoglycans stimulate osteoblast differentiation in vitro. Aims: To characterise heparan sulphate structures that support and enhance osteogenesis and have the potential for tissue engineering. Experiment 1. In order to further investigate the role of heparan-sulphate proteoglycans (HSPGs) in osteogenesis we supplemented cultures of differentiating rat osteo-blasts with sodium chlorate (an inhibitor of the enzyme that sulphates GAG chains) or 4-methylumbelliferyl-b-D-xyloside, BDX (an artificial acceptor of GAG chain synthesis). Interestingly the addition of chlorate to our culture system significantly stimulated alkaline phosphatase levels and increased the area of Von Kossa stained bone-like nodules. Whereas, when BDX was added to differentiating rat osteoblasts there was no increase in alkaline phosphatase activity or nodule area. Experiment 2. Further characterisation of the HSPGs in chlorate treated osteoblasts showed that whilst they were less sulphated than untreated cells (as shown by low salt elution from an anion exchange chromatography column) they were much more abundant. These observations led us to hypothesise that less sulphated forms of heparan sulphate may well stimulate osteo-blast differentiation. Experiment 3. To test this hypothesis we took the fully sulphated form of heparan sulphate, heparin and selectively desulphated it using DMSO/methanol (9:1) at 97°C and specifically N-resulphated or N-acetylated. These partially desulphated heparins were then added to osteoblasts cultured under osteogenic conditions. Quantification of bone nodule formation showed that specifically desulphated heparin significantly increased mineralised areas compared to controls whilst the addition of heparin inhibited osteogenesis. How these modified heparan sulphates exert their effect on bone cells is unknown, but a well characterised role of heparan sulphate is the support of FGF signalling. In preliminary studies we have shown through the activation of p42/44 MAPK and proliferation assays that the modified heparan sulphates are able to support FGF signalling in bone cells. Experiment 4. Currently were are attaching our desulphated heparin to biomaterial scaffolds and examining osteoblast attachment and migration/ingrowth in cell culture. Conclusion: We have isolated heparan sulphate chains that demonstrate osteogenic properties and have the potential for enhancing biological interactions of orthopaedic implant materials

Staphylococcus aureus is the main cause of osteomyelitis and forms biofilm and staphylococcal abscess communities (SACs) in humans. While S. aureus has several toxins with specificity for human targets and working with human host cells would be preferred, for SACs no in vitro models, two-dimensional (2D) or three-dimensional (3D), have been described in literature to date. Advanced 3D in vitro cell culture models enable the incorporation of human cells and resemble in vivo tissue more closely than conventional 2D cell culture. Therefore, the aim of this study was to develop an in vitro model of SACs by using a 3D system. The model should allow for studies into antibiotic tolerance and S. aureus - human host cells interactions. With a clinical isolate (S. aureus JAR) or a lab strain (S. aureus ATCC 49230-GFP), SACs were grown in a collagen gel (1.78 mg/ml, Gibco) supplemented with 200 µl human plasma at 37 °C. Transmission and scanning electron microscopy was used to obtain a detailed overview of SACs, whereas immunofluorescent stainings were done to determine whether the pseudocapsule around SACs consist of fibrin. Antibiotic tolerance of SACs was assessed with 100× the minimal inhibitory concentration (MIC) of gentamicin (Roth). Bacterial clearance of non-establised SACs and established SACs with or without pseudocapsule was determined by exposure to differentiated PLB neutrophil-like cells (differentiation with 1.25% DMSO and 5% FBS for 5 days; dPLB) or primary neutrophils isolated with lymphoprep from fresh heparin blood. Degradation of the pseudocapsule was done with 7.5 µl/ml plasmin (Sigma). Colony forming unit (CFU) counts were performed as quantification method. Statistical analysis was performed with the ANOVA multiple comparison test or, when data was not normally distributed, with a Mann-Whitney U test. We have developed a 3D in vitro model of SACs which after overnight growth were on average 200 micrometers in diameter, consisted of 8 log10 CFUs and were surrounded by an inner and outer fibrin pseudocapsule. The in vitro grown SACs tolerated 100× the MIC of gentamicin for 24h and did not significantly differ from control SACs (p=0.1000). dPLB neutrophil-like cells or primary neutrophils did not clear established in vitro SACs (p=0.1102 and p=0.8767, respectively). When the fibrin pseudocapsule was degraded by the enzyme plasmin, dPLB neutrophil-like cells or primary neutrophils caused for a significant decrease in total CFU compared the SACs that did had a pseudocapsule (p=0.0333 and p=0.0272, respectively). The in vitro SACs model offers a tool for host-pathogen interaction and drug efficacy assessments and is a valuable starting point for future research