Consensus recommendations for the use of FEIBA(®) in haemophilia A patients with inhibitors undergoing elective orthopaedic and non-orthopaedic surgery.

A growing number of publications have described the efficacy and safety of FEIBA as a first-line haemostatic agent for surgical procedures in haemophilia A patients with high-responding FVIII inhibitors. The aim of this study was to provide practical guidance on patient management and selection and also to communicate a standardized approach to the dosing and monitoring of FEIBA during and after surgery. A consensus group was convened with the aims of (i) providing an overview of the efficacy and safety of FEIBA in surgery; (ii) sharing best practice; (iii) developing recommendations based on the outcome of (i) and (ii). To date there have been 17 publications reporting on the use of FEIBA in over 210 major and minor orthopaedic and non-orthopaedic surgical procedures. Haemostatic outcome was rated as 'excellent' or 'good' in 78-100% of major cases. The reporting of thromboembolic complications or anamnestic response to FEIBA was very rare. Key to the success of FEIBA as haemostatic cover in surgery is to utilize the preplanning phase to prepare the patient both for surgery and also for rehabilitation. Haemostatic control with FEIBA should be continued for an adequate period postoperatively to support wound healing and to cover what can in some patients be an extended period of physiotherapy. Published data have demonstrated that FEIBA can provide adequate, well tolerated, peri and postoperative haemostatic cover for a variety of major and minor surgical procedures in patients with haemophilia A. The consensus recommendations provide a standardized approach to the dosing and monitoring of FEIBA.

Factor IX replacement to cover total knee replacement surgery in haemophilia B: a single-centre experience, 2000-2010.

Total knee replacement (TKR) is a well recognized treatment for haemophilic arthropathy. Successful haemostasis can be achieved by bolus doses or continuous infusion (CI) using either recombinant (r) or plasma-derived (pd) factor IX (FIX). We retrospectively analysed our experience of factor replacement to cover TKR in haemophilia B patients and explored factors related to FIX use during surgery. Between 2000 and 2010, 13 primary TKRs were performed in 11 haemophilia B patients. Operations were performed by the same surgeon using standard techniques. Median age was 58 years (42-79). An adjusted CI protocol was used for 5 days followed by bolus doses. FIX:C was maintained at 100 IU dL(-1) in the immediate postoperative period. There was no excess haemorrhage. There was no evidence of thrombosis or infection. All patients received mechanical thromboprophylaxis and only one chemical. CI was used in seven cases. Ten patients received pdFIX. Median hospital stay was 14 days (8-17). Median factor usage was 999 IU kg(-1) (768-1248). During CI, factor consumption was 695 IU kg(-1), 691 IU kg(-1) and 495 IU kg(-1) for BeneFix®, Replenine® and Haemonine, respectively. Clearance of both pdFIX and rFIX reduced during CI. All operations were uncomplicated. The decreased clearance in the CI setting reduced the amount of FIX required to maintain a therapeutic level. This reduction was greater with pdFIX and may be related to pharmacokinetic differences between pdFIX and rFIX. Given the excellent safety profile of the pdFIX products, CI of FIX and particularly pdFIX is safe, efficacious and convenient.

Total knee replacement in patients with end-stage haemophilic arthropathy: 25-year results.

Haemophilia is an x-linked inherited bleeding disorder which can cause severe arthropathy. We have reviewed the results of 70 primary total knee replacements (TKR) performed in 57 haemophilic patients between 1983 and 2007. The functional results were assessed using the Hospital for Special Surgery (HSS) knee scoring system and Kaplan-Meier survivorship analysis. Six patients died. HSS scores were available for 60 TKRs at a mean follow-up of 9.2 years (2 to 23); 57 (95%) had good or excellent results. Deep infection was recorded in one patient. Kaplan-Meier analysis using infection and aseptic loosening as endpoints showed the survival rate at 20 years to be 94.0%. A reduction in infection, spontaneous haemarthrosis and improvement in the quality of life were noted to justify surgery in our series of patients with a mean age of 43 (25 to 70). We have found that using the latest techniques of continuous infusion of clotting Factor have significantly helped to reduce the complication rates and have achieved results which match those of the non-haemophilic population undergoing TKR.

Consensus protocol for the use of recombinant activated factor VII [eptacog alfa (activated); NovoSeven] in elective orthopaedic surgery in haemophilic patients with inhibitors.

Patients with haemophilia complicated by inhibitors have a significant burden of joint disease, which is associated with a negative impact on their quality of life. Successful elective orthopaedic surgery can result in decreased bleed frequency into a new joint, less time spent in hospital, increased mobility and improved well being. This paper describes a new protocol for use of recombinant activated factor VII (rFVIIa) in elective orthopaedic surgery, based on a review of published data as well as the personal experience of a group of expert physicians. The protocol offers guidance on the planning of the surgery and preoperative testing as well as the bolus schedule for rFVIIa and advice on the concomitant use of antifibrinolytic agents and fibrin sealants. A total of 10 operations involving 13 procedures in eight patients in five comprehensive care centres have been undertaken until now using the protocol, which employs an initial bolus dose of rFVIIa in the range of 120-180 microg kg(-1) to cover surgery. The clinical experience reported here encompasses all cases of elective orthopaedic surgery using rFVIIa as initial treatment carried out in the UK and Republic of Ireland over the last 2 years. In all cases, there was good control of haemostasis during surgery and the final outcome was rated as 'excellent' or 'extremely satisfactory' by the reporting clinicians. Although the initial cost of product to cover surgery such as arthroplasty is high, it needs to be borne in mind that this may be offset in subsequent years by savings resulting from avoidance of bleeding episodes in the affected joint.

An outline of the current orthopaedic management of haemophilic disease of the upper limb.

There remains a relative paucity in the literature regarding upper limb manifestations of haemophilic arthropathy. Haemophilia has a wide range of clinical manifestations, often presenting with orthopaedic complications. These arise from multiple haemarthroses which exact a cumulative toll on the fabric of the joints. Although the lower limbs are predominantly affected due to their load-bearing nature, upper limb disease is common. This arises from the mechanical demands on the upper limb as the elbow and shoulder become partially weight bearing on use of walking aids such as elbow crutches.

Primary malignancies mistaken for pseudotumours in haemophilic patients.

Pseudotumours are a rare complication of haemophilia. Surgery undertaken for pseudotumour on a lesion that is subsequently found to be malignant can be expected to adversely affect patient outcome. We present six case reports found from a literature search of patients with haemophilia who underwent surgery on what was a primary malignancy misdiagnosed as a pseudotumour and give a subsequent discussion.

Optical leaky waveguide biosensors for the detection of organophosphorus pesticides.

Organophosphorus (OP) pesticides can be rapidly detected by integrating organophosphorus hydrolase with an optical leaky waveguide biosensor. This enzyme catalyses the hydrolysis of a wide range of organophosphorus compounds causing an increase in the pH. Thus, the direct detection of OP is possible by monitoring of the pH changes associated with the enzyme's activity. This article describes the use of an optical, leaky waveguide clad with absorbing materials for the detection of OP pesticides by measuring changes in refractive index, absorbance and fluorescence. In the most effective configuration, a thick sensing layer was used to increase the amount of immobilized enzyme and to increase the light interaction with the sensing layer, resulting in a greatly enhanced sensitivity. The platforms developed in this work were successfully used to detect paraoxon and parathion down to 4 nM concentrations.

Heterotropic bone formation as a complication of elective joint replacement in haemophilic patients - a case report and literature review.

We report two cases of this rare postoperative condition. Both patients having undergone extensive surgery to their hips, developed increased bone growth in the soft tissue of the hip, accounting for the reduced range of movement, pain and stiffness. Plain x-rays taken confirmed the presence of heterotopic ossification, also known as a variant of myositis ossificans. We review the literature and discuss treatment options of this rare condition in patients with end-stage haemophilic arthropathy.

Haemophilic arthropathy of the elbow.

Patients affected by haemophilia commonly have recurrent intra-articular bleeding which leads to progressive destruction and instability of joints. Severe arthropathy of the elbow is complicated by pain, stiffness and loss of function which can be debilitating. Conservative measures such as analgesics, physiotherapy and orthotics are commonly used in the management of these patients. Surgery is considered when conservative measures fail to control the symptoms. Total elbow replacement is now increasingly performed with the advances made in factor replacement therapy and evolution of better implants and techniques of total elbow arthroplasty. The pathogenesis, clinical features and radiological changes of haemophilic arthropathy of the elbow are described in this review article.

Elective orthopaedic surgery for inhibitor patients.

We report on a series of 108 elective orthopaedic surgical procedures. It includes 88 radiosynoviortheses and 20 major orthopaedic procedures, performed on 51 patients at nine centres worldwide. The average age of patients was 28.5 years (range 5-40 years), and the average follow-up time was 2 years (range 1-5 years). There were 82 good results, 15 fair and 11 poor. In the synoviorthesis group (41 patients, 88 synoviortheses) the average age was 14.3 years (range 5-40 years) and the average follow-up was 6.5 years (range 1-10 years). There were 66 good results, 14 fair and eight poor. There were no complications. In the group of major orthopaedic procedures, the average age of the 10 patients was 32.5 years (range 27-40 years), and the average follow-up was 2.3 years (range 1-5 years). There were 16 good results, one fair and three poor. Postoperative bleeding complications occurred in three of the 20 major orthopaedic procedures performed (15% complications rate). They occurred in three patients treated with insufficient doses of recombinant activated factor VII. Despite such complications, the study has shown that haemophilic patients with inhibitors requiring elective orthopaedic surgery (EOS) can undergo such procedures with a high expectation of success. In other words, EOS is now possible in haemophilic patients with inhibitors, leading to an improved quality of life for these patients. Thorough analysis of each case as part of a multidisciplinary team will allow us to perform elective orthopaedic procedures in patients with inhibitors.

The technique of synoviorthesis.

Synoviorthesis (medical synovectomy) is a commonly utilized procedure employed in the management of recurrent intra-articular bleeds and secondary chronic synovitis in haemophilic patients. The procedure involves the intra-articular administration of an agent in order to induce fibrosis in the inflamed synovium so reducing the bleeding tendency. Such agents may either be chemical based (osmic acid, rifampicin) or radioactive (yttrium, gold or phosphorus). Whichever agent is employed care must be taken to avoid extra-articular complications (radiation burn and/or inflammatory reaction) as a result of extravasation or needle track contamination. The most frequently affected joints in haemophilia are the elbows, knees and the ankles, and to a lesser extent the shoulders and hips. This article outlines the techniques of injection of the five aforementioned joints, with details of the anatomical landmarks to perform the injections correctly. Injection of the elbows, knees and ankles may be carried out simply on an out-patient basis under local anaesthesia. However, it is advisable to perform injection of the shoulder or hip under radiographic control in order to ensure accurate placement. Very young children may require either sedation or a general anaesthetic. Strict asepsis is naturally a paramount requirement.

Classification of traumatic hip dislocation.

The commonly used classification systems of hip dislocation are based on the direction of the dislocation and the presence of associated lesions. However, no rating system can reliably predict the patient's outcome and prognosis based on the initial presentation and classification. In general, patients with anterior dislocations have the best prognosis. Other factors affecting the prognosis are the associated injuries and more importantly the delay between dislocation and reduction.

Acute percutaneous scaphoid fixation. A pilot study.

Fractures of the scaphoid are most common in young men; immobilisation in a cast usually means a long period away from work and athletic activities. Early rigid fixation has been shown to promote a rapid functional recovery, but open reduction and internal fixation is technically demanding with the dangers of damage to the radiocarpal ligaments, the scaphotrapezial joint, and the blood supply of the scaphoid. For minimally displaced or undisplaced B1 or B2 fractures, these problems can be overcome by percutaneous fixation. We report our technique and the results of a pilot study in 15 patients. There was no immobilisation; patients were allowed movement soon after operation, but union was obtained in all at a mean of 57 days (38 to 71). The range of movement after union was equal to that of the contralateral limb and grip strength was 98% of the contralateral side at three months. Patients were able to return to sedentary work within four days and to manual work within five weeks. Our initial results show that percutaneous scaphoid fixation for acute fractures is satisfactory and gives rapid functional recovery.

Knee pain and the infrapatellar branch of the saphenous nerve.

Pain over the front of the knee is common after surgery or trauma but often a definite diagnosis is difficult to make. Over the past year we have seen five cases in which the pain could be ascribed to damage to a branch of the infrapatellar branch of the saphenous nerve. Two were subsequent to trauma and three to surgical procedures. In all five cases surgical exploration gave symptomatic relief. Eight cadaveric knees were prosected to explore further the anatomy of this nerve in relation to the injuries. Injury to one of these branches should be considered in cases of persistent anterior, anteromedial or anterolateral knee pain or neurological symptoms following surgery or trauma.

Ipsilateral total shoulder and elbow prosthetic replacement in a patient with severe haemophilia B.

Since factor replacement concentrates became widely available in the 1970s, total prosthetic replacement of joints in haemophilic patients has become increasingly common, with success particularly in the knee and hip. However, there has been no published series of elbow or shoulder replacements large enough to draw conclusions about the advisability of these procedures in this group of patients. We report a case of prosthetic replacement of the shoulder in a 58-year-old man with haemophilia B, and replacement of the elbow joint of the same limb 21 months later. The results are initially very encouraging, with no pain in either joint since the early post-operative period. There have been no bleeds into either joint since surgery. Ranges of movement are satisfactory. Follow-up is now 37 months for the shoulder and 16 months for the elbow.

Current attitudes to cementing techniques in British hip surgery.

Aseptic loosening is the major problem in hip joint replacement. Improved cementing techniques have been shown to improve the long-term survival of implants significantly. To assess the use of modern cementing techniques in British surgeons, a detailed questionnaire was sent to all Fellows of The British Orthopaedic Association (BOA) regarding cement preparation, bone preparation, cementing technique and prostheses used in total hip arthroplasty. Excluding retired fellows, surgeons who use no cement, and those who had filled in forms inadequately, 668 responded, who between them performed 43,680 hip arthroplasties per year. In this survey, 21 different types of hip prostheses were implanted by the surgeons; 48% of hips implanted were Charnley type. Of the surgeons, 46% used Palacos with gentamicin as their cement for both the femur and acetabulum. For the femur, 44% of surgeons remove all cancellous bone, 40% use pulse lavage, 59% use a brush to clear debris, 94% dry the femur, 97% plug the femur, 76% use a cement gun and 70% pressurise the cement. For the acetabulum, 88% of surgeons retain the subchondral bone, 40% use pulse lavage, 100% dry the acetabulum, 22% use hypotensive anaesthesia and 58% pressurise the cement. Overall only 25% of surgeons (26% of hips implanted) use 'modern' cementing techniques. This has implications for the number of arthroplasties that may require early revision.

Surgical treatment of the rheumatoid hand.

Many rheumatoid patients either present late or are denied access to surgery which would benefit them if undertaken at an early stage. Combined clinics involving physicians, surgeons and therapists allow better assessment and help patients to receive maximum benefit from treatment. An understanding of the principles of surgery of the rheumatoid hand is important in the management of these patients.