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

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

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

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

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

We compared thromboembolic events, major haemorrhage and death after total hip replacement in patients receiving either aspirin or low-molecular-weight heparin (LMWH). We analysed data from the National Joint Registry for England and Wales linked to an administrative database of hospital admissions in the English National Health Service. A total of 108 584 patients operated on between April 2003 and September 2008 were included and followed up for 90 days. Multivariable risk modelling and propensity score matching were used to estimate odds ratios (OR) adjusted for baseline risk factors. An OR <  1 indicates that rates are lower with LMWH than with aspirin. In all, 21.1% of patients were prescribed aspirin and 78.9% LMWH. Without adjustment, we found no statistically significant differences. The rate of pulmonary embolism was 0.68% in both groups and 90-day mortality was 0.65% with aspirin and 0.61% with LMWH (OR 0.93; 95% CI 0.77 to 1.11). With risk adjustment, the difference in mortality increased (OR 0.84; 95% CI 0.69 to 1.01). With propensity score matching the mortality difference increased even further to 0.65% with aspirin and 0.51% with LMWH (OR 0.77; 95% CI 0.61 to 0.98). These results should be considered when the conflicting recommendations of existing guidelines for thromboprophylaxis after hip replacement are being addressed

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

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

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

Aims. Venous thromboembolism (VTE) is a potential complication of foot and ankle surgery. There is a lack of agreement on contributing risk factors and chemical prophylaxis requirements. The primary outcome of this study was to analyze the 90-day incidence of symptomatic VTE and VTE-related mortality in patients undergoing foot and ankle surgery and Achilles tendon (TA) rupture. Secondary aims were to assess the variation in the provision of chemical prophylaxis and risk factors for VTE. Methods. This was a multicentre, prospective national collaborative audit with data collection over nine months for all patients undergoing foot and ankle surgery in an operating theatre or TA rupture treatment, within participating UK hospitals. The association between VTE and thromboprophylaxis was assessed with a univariable logistic regression model. A multivariable logistic regression model was used to identify key predictors for the risk of VTE. Results. A total of 13,569 patients were included from 68 sites. Overall, 11,363 patients were available for analysis: 44.79% were elective (n = 5,090), 42.16% were trauma excluding TA ruptures (n = 4,791), 3.50% were acute diabetic procedures (n = 398), 2.44% were TA ruptures undergoing surgery (n = 277), and 7.10% were TA ruptures treated nonoperatively (n = 807). In total, 11 chemical anticoagulants were recorded, with the most common agent being low-molecular-weight heparin (n = 6,303; 56.79%). A total of 32.71% received no chemical prophylaxis. There were 99 cases of VTE (incidence 0.87% (95% CI 0.71 to 1.06)). VTE-related mortality was 0.03% (95% CI 0.005 to 0.080). Univariable analysis showed that increased age and American Society of Anesthesiologists (ASA) grade had higher odds of VTE, as did having previous cancer, stroke, or history of VTE. On multivariable analysis, the strongest predictors for VTE were the type of foot and ankle procedure and ASA grade. Conclusion. The 90-day incidence of symptomatic VTE and mortality related to VTE is low in foot and ankle surgery and TA management. There was notable variability in the chemical prophylaxis used. The significant risk factors associated with 90-day symptomatic VTE were TA rupture and high ASA grade. Cite this article: Bone Joint J 2024;106-B(11):1249–1256

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

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