Arthroscopic ankle surgery in people with haemophilia.

INTRODUCTION: People with haemophilia (PWH) not administered primary haematological prophylaxis since childhood, that is, those treated haematologically on demand or not treated at all, often experience the degeneration of the ankles, leading to pain and functional impairment. AIM: To analyse the outcomes and complications of arthroscopic ankle surgery performed on PWH. METHODS: For this narrative review of the literature, a search was conducted in PubMed on 2, December 2023, using the keywords "haemophilia", "ankle" and "arthroscopy". Of the 29 articles identified, 15 specifically related to ankle arthroscopy in PWH were selected (inclusion criterion). The remaining articles did not meet this requirement (exclusion criterion) and were therefore eliminated. RESULTS: Arthroscopic procedures (arthroscopic synovectomy, debridement and arthrodesis of the ankle) are increasingly used in the surgical treatment of haemophilic ankle arthropathy. Although arthroscopic ankle surgery offers good outcomes in patients with haemophilia, the procedure is not free of complications, which range from 7.9% for arthroscopic ankle debridement to 13.1% in arthroscopic ankle synovectomy and 17.8% in arthroscopic ankle arthrodesis, respectively. The non-union rate of arthroscopic ankle arthrodesis is 7.1% (2/28). CONCLUSION: Although arthroscopic interventions in the haemophilic ankle (synovectomy, debridement, arthrodesis) offer good functional outcomes, they are associated with a non-negligible rate of complications. Arthroscopic ankle surgery in PWH is major surgery and should be treated as such.

Clinical assessment and point of care ultrasonography: How to diagnose haemophilic synovitis.

BACKGROUND: The ability of clinical tools to identify early joint changes is limited. Synovitis is a fundamental finding in understanding haemophilia activity and the response to its therapies; thus, there is a need for sensitive methods to better diagnose subclinical synovitis early. PURPOSE: Our aim was to compare the frequency with which clinical assessment and ultrasound detected synovial hypertrophy in the most frequently affected joints in patients with haemophilia (elbows, knees and ankles). METHODS: We analysed patients with haemophilia older than 16 years who came to the haemophilia centre for routine follow-up. From the clinical assessment carried out in the consultation, the swelling, pain and history of haemarthrosis were evaluated and compared with the findings of synovial hypertrophy detected by ultrasound. This comparison was also analysed independently for elbows, knees and ankles. RESULTS: A total of 203 joints of 66 patients with haemophilia (mean age 34 years), most of them on secondary, tertiary prophylaxis or on demand treatment, were included. In joints with swelling, pain and history of haemarthrosis, 78% of the joints showed synovial hypertrophy on ultrasound. However, in joints with no swelling, no pain and no history of haemarthrosis, 40% presented subclinical synovial hypertrophy on ultrasound. This percentage was higher in elbows than in knees and ankles. CONCLUSION: In adults with haemophilia, physical examination and point-of-care ultrasound study provide complementary data on their joint disease. However, without ultrasound, the ability to detect subclinical synovitis is considerably reduced, especially in the elbows.

Concomitant use of bypassing agents with emicizumab for people with haemophilia A and inhibitors undergoing surgery.

INTRODUCTION: Surgery in people with haemophilia and factor VIII inhibitors is typically managed with perioperative administration of haemostatic agents to prevent or control the occurrence of bleeding events. Practical experience of surgery in patients with inhibitors who are receiving treatment with emicizumab is growing; however, the novelty of the situation means that standardised guidelines are lacking with regard to the concomitant administration of haemostatic agents, including dose and laboratory monitoring. AIM: To review approaches to haemostatic management during major and minor invasive procedures in patients with haemophilia A and inhibitors, and to provide recommendations for controlling bleeding events. METHODS: A search was conducted, limited to the past 4 years (January 2016-April 2020), pertaining to published evidence of surgery for patients receiving emicizumab. Publications identified from the search were manually reviewed to determine studies and case reports relevant for inclusion. RESULTS: Identified literature and practical experience of the authors were used to build a consensus of practical recommendations for the concomitant administration of haemostatic agents during the perioperative period for elective surgery in patients with inhibitors who are receiving emicizumab. CONCLUSIONS: The current evidence base indicates that surgery can be successfully performed in patients with inhibitors who are receiving emicizumab and that bypassing agents can be used concomitantly. Data from prospective studies are required to further support recommendations for haemostatic management of surgery in patients receiving emicizumab.

Gene Therapy in Hemophilia: Recent Advances.

Hemophilia is a monogenic mutational disease affecting coagulation factor VIII or factor IX genes. The palliative treatment of choice is based on the use of safe and effective recombinant clotting factors. Advanced therapies will be curative, ensuring stable and durable concentrations of the defective circulating factor. Results have so far been encouraging in terms of levels and times of expression using mainly adeno-associated vectors. However, these therapies are associated with immunogenicity and hepatotoxicity. Optimizing the vector serotypes and the transgene (variants) will boost clotting efficacy, thus increasing the viability of these protocols. It is essential that both physicians and patients be informed about the potential benefits and risks of the new therapies, and a register of gene therapy patients be kept with information of the efficacy and long-term adverse events associated with the treatments administered. In the context of hemophilia, gene therapy may result in (particularly indirect) cost savings and in a more equitable allocation of treatments. In the case of hemophilia A, further research is needed into how to effectively package the large factor VIII gene into the vector; and in the case of hemophilia B, the priority should be to optimize both the vector serotype, reducing its immunogenicity and hepatotoxicity, and the transgene, boosting its clotting efficacy so as to minimize the amount of vector administered and decrease the incidence of adverse events without compromising the efficacy of the protein expressed.

Emicizumab: Review of the literature and critical appraisal.

INTRODUCTION: Emicizumab-kywh (ACE910) is a recombinant, humanized, asymmetric bispecific antibody that functions to bring activated FIX (FIXa) and zymogen FX into an appropriate steric conformation to medicate the activation of FX to FXa thereby mimicking the cofactor function of FVIIIa. AIM: The objective of this manuscript was to review the development and potential role for emicizumab in the treatment of patients with haemophilia A with and without inhibitors. METHODS: A Cochrane Library and PubMed (MEDLINE) search focusing on emicizumab in haemophilia was conducted. RESULTS: In total, 37 citations were retrieved and serve as the database for the literature reviewed herein. Once-weekly subcutaneous injection of emicizumab at three dose levels has been shown to be effective as prophylaxis to prevent bleeding in a majority haemophilia A patients with inhibitors to FVIII. Likewise, prevention of bleeding was also observed in more than two thirds of patients without inhibitors to FVIII. One antidrug antibody to emicizumab has been reported in over 600 treated patients, two have developed thromboembolic events and three thrombotic microangiopathy. These thrombotic complications have occurred in conjunction with FVIII-bypassing agents, and none have been observed following recommendations from the manufacturer regarding concomitant use of bypassing agents. The median annual treated bleeding rates were decreased in patients with as well as those without an inhibitor to FVIII. CONCLUSION: The principal advantage of emicizumab is subcutaneous administration and effectiveness irrespective of the presence of inhibitors. Emicizumab could conceivably represent a new epoch in the treatment of people with haemophilia A.

External Fixation vs Intramedullary Nailing for Knee Arthrodesis After Failed Infected Total Knee Arthroplasty: A Systematic Review and Meta-Analysis.

BACKGROUND: The aim of this study is to compare intramedullary nailing with external fixation for knee arthrodesis after failed infected total knee arthroplasty (TKA). Primary outcome is radiographic union. Secondary outcomes include recurrent deep infection, revision arthrodesis, and amputation. METHODS: Systematic review and meta-analysis of studies comparing outcomes from intramedullary nailing and external fixation in patients with infected TKA undergoing arthrodesis procedures was performed. Randomized controlled trials and cohort studies were included. RESULTS: Intramedullary nailing achieves a significantly higher rate of radiographic union compared with external fixation (odds ratio [OR] 5.17, 95% confidence interval [CI] 2.74-9.75, P < .00001) at a mean follow-up of 44.22 months. There is no significant difference in the rate of recurrent deep infection (OR 0.91, 95% CI 0.38-2.15, P = .83) or amputation (OR 0.94, 95% CI 0.23-3.84, P = .93). The rate of revision arthrodesis procedures is significantly lower for intramedullary nailing compared with external fixation (OR 0.28, 95% CI 0.08-0.93, P = .04). CONCLUSION: Intramedullary nailing is more effective than external fixation with respect to several clinically important outcomes. Therefore, we recommend intramedullary nailing for achieving knee arthrodesis as a salvage procedure for infected TKA in the absence of specific indications for external fixation.

Managing Haemophilia for Life: 5th Haemophilia Global Summit.

The 5th Haemophilia Global Summit was held in Barcelona, Spain, in September 2014. The programme was designed by an independent Scientific Steering Committee of haemophilia experts and explored issues relevant to the practical management of haemophilia, as well as key opportunities and challenges for care in the future. The topics outlined in this supplement were selected by the Scientific Steering Committee for their relevance to improving haemophilia care globally. In this supplement from the meeting, Gerry Dolan explores pharmacokinetics and dynamics in haemophilia, and Gerry Dolan and Ian Jennings jointly address the role of the laboratory in haemophilia care. The potential benefits of low-dose prophylaxis regimens for people with haemophilia in the developing world are reviewed by Jerzy Windyga, and the question of whether 'Future haemophilia research should be undertaken in the developing world' is debated by Jerzy Windyga and Cedric Hermans. Management strategies for ankle arthropathy are discussed by Sébastien Lobet and E. Carlos Rodríguez-Merchán, and the use of ultrasound for the early detection of haemophilic arthropathy is addressed by Matteo Nicola Dario Di Minno and Víctor Jiménez-Yuste. Finally, the role of patients in the future of haemophilia care is reviewed by Brian O'Mahony.

Hemophilic arthropathy of the elbow: prophylaxis, imaging, and the role of invasive management.

Hemophilia is an X-linked recessive deficiency of clotting factor VIII (hemophilia A) or IX (hemophilia B) that can result in hemarthrosis of various joints, including the elbow. Left unchecked, this can lead to progressive joint destruction and significant morbidity. Appropriate management of the elbow joint through prophylactic measures, accurate imaging, and timely intervention is essential. Replacing or supplementing deficient factor with a plasma-derived or recombinant factor concentrate can minimize bleeding episodes. Joints should be routinely monitored for damage. Plain films offer an inexpensive window into bone disease and joint space changes but lack soft tissue detail and may not detect early changes. Magnetic resonance imaging provides a high level of detail but may be limited by its cost and need for sedation in younger patients. Ultrasound may not achieve the same level of resolution as magnetic resonance imaging, but it is increasingly used as a convenient, effective, and relatively inexpensive alternative. Patients who experience hemarthrosis of the elbow with joint damage often require more invasive treatment. Radiosynovectomy and arthroscopic synovectomy are effective at minimizing pain and preventing future bleeding episodes, whereas extensive joint damage may necessitate total elbow replacement.

Can Isolated Tibial Component Revision Be an Alternative to Isolated Aseptic Loosening of the Tibial Component in Total Knee Arthroplasty?

This article reviews the information on isolated tibial component revision for isolated aseptic loosening of the tibial component in total knee arthroplasty (TKA). It summarizes the results of recent major studies published in PubMed since the beginning of the search engine until 28 March 2023. Sixty-five articles were found, of which only five were analyzed because they were directly related to the title of this article. At 5-year follow-up isolated tibial revision and both-component (femoral and tibial) revision for aseptic loosening did not differ with regard to failures of the implant, adverse events, and clinical outcomes.

Primary Total Knee Arthroplasty in Hemophilia and Allied Disorders: Revision Rates and Their Causes.

When patients with hemophilia and allied disorders (von Willebrand disease and other congenital bleeding disorders) do not receive adequate primary hematologic prophylaxis from infancy, their joints will suffer knee joint degeneration; when such joint degeneration becomes very advanced (painful and disabling) despite previous conservative treatment, the only way to alleviate the problem will be to implant a primary total knee arthroplasty (TKA). The literature has shown that twenty years after implantation, 71% of primary TKAs are still functional; on the other hand, 18% have to be revised as a consequence of periprosthetic joint infection (PJI). The main causes of revision total knee arthroplasty are PJI and aseptic loosening (39% each).

Re-revision Total Knee Arthroplasty: Causes, Risk Factors and Results.

The rate of re-revision total knee arthroplasty (TKA) ranges between 4% and 10%, depending on the cause of the procedure. Periprosthetic joint infection (PJI) and periprosthetic fracture are the main causes of re-revision TKA. The likelihood of implant survival of re-revision TKA diminishes with each subsequent revision, with PJI being the main cause of multiple revisions. Acute early aseptic revision TKA (within 90 days of surgery) involves a high risk of re-revision at 2 years and a high risk of subsequent PJI. The use of antibiotic-loaded cement is associated with lower risk of re-revision. Patients younger than 50 years experiencing aseptic revision TKA have a 1 in 3 risk of re-revision. Patients revised for instability or having prior TKA revisions have the highest risk of re-revision at 10 years. Patients younger than 55 years experiencing revision TKA have a 5-year revision-free survival of 80%.

Total Hip Arthroplasty in Hemophilic Patients: are their Results Similar to those of Nonhemophilic Patients?

Total hip arthroplasty (THA) is the mainstay therapy for patients with terminal hemophilic arthropathy of the hip. However, the largest case series published between 2017 and 2023 in the literature on THA in patients with hemophilia have found a higher 1-year infection rate (8.1% versus 3.4%) in hemophilia patients than in the general population, a higher rate of in-hospital bleeding complications (38.7% versus 16.1%), a higher length of stay (6 days versus 3 days) and a higher 30-day readmission rate (22.6% versus 4.1%). Finally, a lower 5-year survival rate has also been observed in hemophilia patients than in the general population (91.9% versus 95.3%). In the last decade there have been dramatically positive improvements in implant designs and hematological treatment, and therefore it does not seem that THA in hemophilia is so far from that in osteoarthritic patients.

Mortality rate after total knee arthroplasty or total hip arthroplasty in patients with a history of liver transplant.

In this editorial I comment on the article by Ahmed et al published in a recent issue of the World J Orthop 2023; 14: 784-790. It is well known that patients who have undergone a liver transplant (LT) may need to have a total hip arthroplasty (THA) or total knee arthroplasty (TKA) implanted. Ahmed et al stated that the mortality rate in these patients was similar to the one of the general population. However, there are three articles previously published that found higher mortality in LT patients who experienced THA/TKA than in the general population (individuals without LT). Therefore, in this Editorial I would like to point out that there is controversy in the literature regarding whether LT patients undergoing THA/TKA have higher mortality than the general population. Therefore, future research should attempt to resolve this controversy.

Discoid LaterL Meniscus: A Concise Literature Update.

Discoid lateral meniscus (DLM) is the most frequent congenital variant of the lateral meniscus, which is prone to degeneration and tears, and frequently causes knee osteoarthritis. The purpose of this article has been to analyze the publications made during 2023 on DLM. The main conclusions of the analysis were as follows: MRI assessment might be helpful to diagnose DLM and detect the presence of instability: two main factors in the decision to perform surgery. Arthroscopic assessment should be utilized in conjunction with MRI findings for complete DLM diagnosis. Restoring the normal shape, retaining adequate width and thickness, and ensuring the stability of the remnant DLM is essential to sustaining the physiological function of the meniscus and preserving the knee. Partial meniscectomy with or without repair should be the first-line treatment when feasible, given that the clinical and radiological long-run results of total or subtotal meniscectomy are worse.

Ankle arthrodesis and total ankle replacement in patients with congenital bleeding disorders suffering from severe ankle arthropathy.

INTRODUCTION: In patients with congenital bleeding disorders suffering from severe ankle arthropathy, when conservative treatment and joint-preserving surgical techniques fail, there are two possible non-joint-preserving options: ankle arthrodesis (AA) and total ankle replacement (TAR). AREAS COVERED: The scope and aim of this article was to analyze the current role of AA and TAR in patients with congenital bleeding disorders suffering from severe ankle arthropathy. EXPERT OPINION: In patients with congenital bleeding disorders, both TAR and AA provide good results, mainly in terms of pain relief, although they are not exempt from complications (between 0% and 33% in TAR and between 5% and 23.5% in AA). The current controversy about which of the two surgical techniques, TAR or AA, gives better results, the current literature is not able to resolve it in patients with congenital bleeding disorders. While this question is being answered, my opinion regarding patients with congenital bleeding disorders is that the age of the patient must be taken into account. Given known prosthetic survival rates, the older the patient, the more we might be inclined to indicate TAR. Conversely, AA may be more appropriate for relatively young patients.

Intraosseous Regional Administration of Vancomycin Prophylaxis for Primary and Revision Total Knee Arthroplasty.

The advantages of prophylaxis with intraosseous regional administration (IORA) of vancomycin for periprosthetic joint infection (PJI) in primary and revision total knee arthroplasty (TKA) include the ability to deliver antibiotics directly to the surgical bed and avert systemic delivery; the ability to precisely time and quickly administer vancomycin to achieve the highest concentrations at the beginning and throughout the surgical procedure; and the ability to avert several common and potentially serious adverse effects of intravenous vancomycin. Indications for IORA of vancomycin prophylaxis include the following clinical scenarios: revision TKA; obesity; diabetes; beta-lactam allergy; known colonization with methicillin-resistant Staphylococcus aureus (MRSA); individuals coming from institutions with a high MRSA incidence; previous ligamentous surgical procedure or osteotomy; current or recent smokers; in the primary TKA setting if the individual is considered high-risk as defined by the criteria above; and during reimplantation following 2-stage exchange for PJI.

Complications of ankle arthroscopy: frequency, prevention, and treatment.

The complication rate of ankle arthroscopy (AA) ranges from 3.5% to 14%. To avoid such complications, it is essential to have a thorough understanding of the anatomy of the ankle, to perform the procedure very carefully and with appropriate instrumentation, and to use a non-invasive distraction technique. The most frequent complications are neurological (cutaneous nerve injuries), which are usually caused by direct injury during arthroscopic portals or by a distracting pin when using an invasive distraction technique. They usually resolve spontaneously within a few months. The iatrogenic formation of a pseudoaneurysm is a severe but extremely rare complication (an incidence of 0.008%). There are several treatments for pseudoaneurysms: external compression; direct thrombin injection, surgical intervention (resection of the damaged segment of the artery and reconstruction with a reversed long saphenous vein interposition graft), and endovascular embolisation. Other rare complications include wound infections (localised superficial infection), problems at the portal incisions (prolonged portal drainage, residual pain in the portal, portal scar dehiscence, cyst at the portal site), type I complex regional pain syndrome, instrument breakage, painful scars and nodules, and a number of other rarer complications. In conclusion, when performing AA, it is important to remember the potential complications and try to avoid them. When they do occur, it is essential to diagnose and treat them appropriately.

Knee replacement surgery in a patient with acquired von Willebrand disease: a case study with recommendations for patient management.

Introduction and importance: Acquired von Willebrand disease (AvWD) is a rare underdiagnosed bleeding disorder caused by alterations in the levels of the major blood-clotting protein von Willebrand factor (vWF). The clinical and laboratory parameters of AvWD are similar to congenital vWD, but it is found in individuals with no positive family history with no underlying genetic basis. The disease remains multifactorial and incompletely understood. Proposed mechanisms include the development of autoantibodies to vWF, absorption of high molecular weight vWF multimers that impair normal function, shear stress induced vWF cleavage and increased proteolysis.The aetiology of the disease is variable, the most common being hematoproliferation, lymophoproliferation, myeloproliferation and autoimmune and cardiovascular disorders. Consensus and protocols for AvWD patients that require major surgery are currently lacking. Patients with AvWD can experience thrombotic events during surgery as a result of therapeutic interactions with pro-thrombotic risk factors. Case presentation: Here, the authors report a patient with AvWD requiring a knee prosthesis implantation due to chronic pain, limited range of motion and functional impairment. The patient had a high risk of bleeding during surgery and was at risk of thrombosis due to age and obesity. Clinical discussion: Perioperative care required a collaborative approach and the management of bleeding. The patient was administered vWF concentrate Willfact lacking Factor VIII to prevent haemorrhage and to minimize the risk of thrombosis. Conclusion: The treatment was effective and well-tolerated. The authors use this information to provide recommendations for AvWD patients for whom major surgery is indicated.

Locking Attachment Plate for the Surgical Treatment of Periprosthetic and Periimplant Fractures: Long-Term Follow-Up.

Objectives: The surgical management of periprosthetic fractures (PPF) and periimplant fractures (PIF) can be challenging. The locking attachment plate (LAP) was proposed in recent years for the osteosynthesis of such fractures. The aim of this study was to assess the experience of a third-level hospital with LAP for the treatment of PPF and PIF, and analyse the clinical outcomes. Methods: Data were prospectively collected and analysed from all patients whose PPF/PIF was treated surgically with LAP in a third-level hospital from June 2018 to June 2022. All fractures were postoperative low-energy femur fractures. The minimum follow-up period was six months. Results: Thirty-eight patients (31 women) met the eligibility criteria. The mean age was 86.3 years. The median time until surgery was 4 days. A mean of 3.61 screws were used for each LAP. The mean femur plate length was 14 holes, and the mean working length 7.1 holes. The median hospital stay was nine days. The mean follow-up was 19.56 months. At one month, 12 patients tolerated partial weight-bearing. Five patients walked independently indoors. One patient had died and seven patients were readmitted. At six months, six more patients had died. Fifteen patients tolerated full weight-bearing (FWB). Nine patients walked independently indoors, six outdoors. Twenty-five patients reached fracture consolidation without malalignment. Nine patients were readmitted. At 12 months, another patient had died. Seventeen patients tolerated FWB. Eleven patients walked independently indoors, six outdoors. Twenty-five patients achieved fracture consolidation without malalignment. Five patients were readmitted. Fourteen patients crossed the two-year postoperative threshold. All achieved fracture consolidation. Two patients passed the 4-year postoperative milestone. Conclusion: The clinical results of patients whose PPF or PIF was treated with the LAP are promising. This fixation method is a viable option to be considered when planning surgery for such fractures.