Severe Haemophilic Arthropathy Research Articles

Biomarkers Involved in the Pathogenesis of Hemophilic Arthropathy.

Hemophilia, which is a rare disease, results from congenital deficiencies of coagulation factors VIII and IX, respectively, leading to spontaneous bleeding into joints, resulting in hemophilic arthropathy (HA). HA involves complex processes, including synovial proliferation, angiogenesis, and tissue remodeling. Despite ongoing research, factors contributing to HA progression, especially in adults with severe HA experiencing joint pain, remain unclear. Blood markers, particularly collagen-related ones, have been explored to assess joint health in hemophilia. For example, markers like CTX-I and CTX-II reflect bone and cartilage turnover, respectively. Studies indicate elevated levels of certain markers post-bleeding episodes, suggesting joint health changes. However, longitudinal studies on collagen turnover and basement membrane or endothelial cell markers in relation to joint outcomes, particularly during painful episodes, are scarce. Given the role of the CX3CL1/CX3XR1 axis in arthritis, other studies investigate its involvement in HA. The importance of different inflammatory and bone damage biomarkers should be assessed, alongside articular cartilage and synovial membrane morphology, aiming to enhance understanding of hemophilic arthropathy progression.

Proteomic exploration of potential blood biomarkers in haemophilic arthropathy.

The pathophysiology of haemophilic arthropathy (HA) is complex and largely undefined. Proteomic analyses provide insights into the intricate mechanisms of the HA.Our study aimed to identify differentially expressed proteins in relation to the severity of HA, explore their pathophysiological roles, and evaluate their potential as HA biomarkers. Our cross-sectional observational study encompassed 30 HA patients and 15 healthy subjects. Plasma samples were pooled into three groups of 15 samples from those with severe haemophilic arthropathy (sHA), mild haemophilic arthropathy (mHA) and healthy controls. Proteomic analysis was performed using liquid chromatography-mass spectrometry. The severity of HA was assessed using the World Federation of Haemophilia Physical Examination Score and ultrasonography following the Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) guidelines. A total of 788 proteins were identified, with 97% of the uniquely identified proteins being expressed in all analysed groups. We identified several up and downregulated proteins across the groups that were mainly related to inflammatory and immunity-modulating processes, as well as joint degeneration. We highlighted ten proteins relevant for the development of HA: cathepsin G, endoplasmic reticulum aminopeptidase 2, S100-A9, insulin-like growth factor I, apolipoprotein (a), osteopontin, pregnancy zone protein, cartilage oligomeric matrix protein, CD44, and cadherin-related family member 2. Our analysis identified several proteins that shed further light on the distinctive pathogenesis of HA and could serve for biomarker research. However, these results need to be validated on a larger patient group.

Outcome measures analysis following total knee arthroplasty in patients with severe haemophilic arthropathy of the knee.

Total knee arthroplasty (TKA) has been the gold standard for treating severe haemophilic arthropathy of the knee when all conservative measures fail. However, performing a TKA in patients with haemophilic arthropathy is difficult due to severe joint deformity and destruction, and poor bone quality. The aim of the present study was to evaluate the short-term results of TKA in the treatment of knee haemophilic arthropathy in a tertiary referral centre, with an emphasis on health-related quality of life and knee function. A prospective study was conducted that included 19 male patients with end-stage haemophilic knee arthropathy who underwent TKA in a tertiary referral centre. Clinical outcome and health-related quality of life were assessed by the Western Ontario and McMaster Universities Arthritis (WOMAC) index and the Short Form-36 (SF-36) both pre-operatively and at 1-year post-operatively. The mean age of the patients was 50.37±7.63 years (range, 40-65 years). Pre-operative health-related quality of life was impaired in all patients in all SF-36 domains but was markedly improved after TKA. Knee function in all dimensions (pain, stiffness and physical function), as measured by the WOMAC questionnaire, significantly improved after TKA. Pre-operative pain, stiffness and function, along with total WOMAC score, were strongly and negatively correlated with pre-operative SF-36. Overall, the present study indicated a significant improvement in quality of life and clinical outcome after TKA in patients with advanced haemophilic arthropathy. More studies with longer follow-up periods in a larger population are needed to fully elucidate the mid- and long-term values of TKA in haemophilic patients.

Mesenchymal Stromal Cells Prevent Blood-induced Degeneration of Chondrocytes in a New Model of Murine Hemarthrosis

Hemophilia is a rare congenital bleeding disorder caused by deficiency in coagulation factors VIII or IX, which is treated with prophylactic clotting factor concentrates. Nevertheless despite prophylaxis, spontaneous joint bleedings or hemarthroses still occur. The recurrent hemarthroses lead to progressive degradation of the joints and severe hemophilic arthropathy (HA) in patients with moderate and even mild forms of the disease. In absence of disease modifying treatment to stop or even delay HA progression, we aimed at evaluating the therapeutic potential of mesenchymal stromal cells (MSCs)-based therapy. We first developed a relevant and reproducible in vitro model of hemarthrosis relying on blood exposure of primary murine chondrocytes. We found that 30% whole blood for 4 days allowed to induce the characteristic features of hemarthrosis including low survival of chondrocytes, apoptosis induction, and dysregulation of chondrocyte markers in favor of a catabolic and inflammatory phenotype. We then evaluated the potential therapeutic effects of MSCs in this model using different conditions of coculture. Addition of MSCs improved the survival of chondrocytes when added either during the resolution or the acute phases of hemarthrosis and exerted a chondroprotective effect by enhancing the expression of anabolic markers, and reducing the expression of catabolic and inflammatory markers. We here provide the first proof-of-concept that MSCs may exert a therapeutic effect on chondrocytes under hemarthrosis conditions using a relevant in vitro model, thereby confirming a potential therapeutic interest for patients with recurrent joint bleedings.

Structural changes after ankle joint distraction in haemophilic arthropathy: an explorative study investigating biochemical markers and 3D joint space width.

Ankle joint distraction (AJD) is a promising treatment for patients with severe haemophilic ankle arthropathy (HAA). However, some patients showed no clinical improvement after AJD and these differences may be related to structural differences. Primarily to quantify the structural changes after AJD in patients with HAA by the use of 3D joint space width (JSW) measurements and biochemical markers and secondarily to correlate these findings with clinical pain/function. Patients with haemophilia A/B who underwent AJD were included for this study. Bone contours on MRI (performed before and 12 and 36 months after AJD) were drawn manually and percentage change in JSW was calculated. Blood/urine (before and 6, 12, 24 and 36 months after AJD) was collected for biomarker measurement (COMP, CS846, C10C, CALC2, PRO-C2, CTX-II) and combined indexes of markers were calculated. Mixed effects models were used for analyses on group level. Structural changes were compared with clinical parameters. Eight patients were evaluated. On group level, percentage changes in JSW showed a slight decrease after 12 months followed by a non-statistically significant increase in JSW after 36 months compared to baseline. Biochemical marker collagen/cartilage formation also showed an initial decrease, followed by a trend towards net formation 12, 24 and 36 months after AJD. On individual patient level, no clear correlations between structural changes and clinical parameters were observed. Cartilage restoration activity on group level in patients with HAA after AJD was in concordance with clinical improvements. Correlating structural modifications with clinical parameters in the individual patient remains difficult.

POSTER ABSTRACTS

POSTER ABSTRACTS

Perioperative Monitoring with Global Coagulation Test in Severe Hemophilia a without Inhibitor on Emicizumab Prophylaxis Undergoing Orthopedic Surgery

INTRODUCTION Emicizumab is a bispecific antibody used to prevent bleeding episodes in patients with severe hemophilia A (PwHA) without inhibitor. However, using FVIII to manage breakthrough bleeding or invasive procedures in patients without inhibitors remains necessary. Current guidelines recommend using chromogenic FVIII (FVIII:C) levels based on bovine reagents to monitor the hemostatic response to the combination of both drugs. However, the perioperative hemostatic management of PwHA undergoing prophylaxis with emicizumab and FVIII remains challenging. Here we describe the hemostatic management and monitoring using global coagulation test of two PwHA without inhibitor on emicizumab prophylaxis undergoing orthopaedic surgery with FVIII. METHODS Perioperative monitoring for two patients was performed, measuring FVIII:C levels using bovine-derived reagents. Samples for global coagulation test were collected in tubes with Corn Trypsin Inhibitor to prevent activation of the contact pathway. Clotting time (CT) was evaluated by Rotational Thromboelastometry (ROTEM®) using whole blood activated by a low concentration of tissue factor (TF) solution (final dilution 1:50,000 of EXTEM reagent) plus recalcification. Thrombin Peak (TP) was assessed by thrombin generation test (TGT) in plasma, also using a low amount of TF and phospholipids (PPP-LOW, Stago). ROTEM and TGT were performed in samples collected before and after FVIII administration during the perioperative process. Samples obtained before FVIII dosing were also spiked in vitro with equivalent therapeutic amounts of FVIII products. RESULTS Patient 1 is a 55-year-old male with severe HA under EMI prophylaxis (1.5 mg/week). He underwent an ankle arthrodesis with osteosynthesis due to severe hemophilic arthropathy. Plasma-derived FVIII/FVW concentrate (pdFVIII/FVW) was used to provide effective hemostatic coverage during the procedure. He received the first dose before surgery and the last dose on day +7 after surgery. The postoperative course was uneventful, and he was discharged on day +4. Patient 2 is a 52-year-old male with a medical history of HIV infection, lymphoma in complete remission and severe HA on EMI prophylaxis (6 mg every four weeks). He was referred to an orthopaedic surgeon due to cubital tunnel syndrome secondary to hemophilic arthropathy that required surgery. A single dose (50 Ul/kg) of extended half-life recombinant FVIII (rFVIII EHL) concentrate was administered before intervention. He was discharged on day +2 in the absence of bleeding complications. He received an additional dose of rFVIII EHL on day +3 after the surgery. Table 1 shows FVIII:C levels in both patients. Both global coagulation tests showed that treatment with emicizumab was insufficient for complete normalization of hemostatic parameters. Clotting time was longer, and thrombin generation was reduced in emicizumab-treated patients compared to healthy controls before the intervention (Figure 1). We observed an improvement and normalization of CT and TP values after administering both FVIII products (plasma-derived or recombinant with EHL) during the perioperative period. This improvement was similar to that obtained with in vitro spiking of equivalent doses of FVIII (Figure 1). Additionally, a correlation between FVIII:C levels and CT and TP values was also observed. CONCLUSIONS The global coagulation test were used to evaluate the hemostatic response to FVIII treatment in PwHA on emicizumab prophylaxis during invasive procedures. Considering that both tests provide a more comprehensive assessment of the hemostatic state of the interaction of emicizumab and FVIII, these tests may complement FVIII levels in complex cases of bleeding or surgery. Funding: ISCIII-FEDER PI19/00631; Catedra UAM-Roche Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Discrepancy between the Results of One-Stage and Chromogenic Factor VIII Assays: Switch in Diagnosis from Mild to Moderate Hemophilia a in Three Cases

Introduction Factor VIII (FVIII) activity can be measured with different methods including one-stage clotting assay (OSA) or chromogenic substrate assay (CSA). Some persons with mild hemophilia A (HA) have a significant discrepancy between the assays which has been previously reported. Discrepancy between these two methods, albeit less frequent, can also lead to a switch in diagnosis from mild to moderate HA. Herein, we report 3 persons with HA (PwHA) whose diagnosis changed from mild to moderate HA after obtaining FVIII levels assessed by CSA. Materials and Methods Data were extracted from the medical records of the PwHA including demographics, bleeding rates, and factor levels. FVIII activity was measured using the OSA on an ACL Top 500 with SynthaSil aPTT reagent (Instrumentation Laboratories Bedford, MA, USA). Factor VIII activity was also determined photometrically via the Chromogenix Coatest® SP4 FVIII chromogenic assay kit (bovine chromogenic FVIII activity, Diapharma Group, West Chester, OH). Results Data were collected from 3 PwHA who were previously diagnosed with mild HA yet were noted to have a bleeding phenotype worse than expected for mild HA (Table-1). Case 1 is 26 years old and had been experiencing multiple joint bleeds. His OSA FVIII level was 6.8%. He was on clotting factor concentrate (CFC) on demand. After having severe hemophilic arthropathy affecting his social life, prophylaxis with CFC was commenced. Significant improvement was observed after the initiation of prophylaxis. His CSA FVIII level was 2.7%, consistent with his bleeding phenotype, and he has been on emicizumab prophylaxis for a year without any bleeding events. Case 2 is 22 years old and had been experiencing frequent muscle bleeds. His OSA FVIII level was 6.1% and CSA FVIII level was 2.7%. He remains on CFC on demand based on his preference despite the frequent bleeding. Case 3 is 15 years old and was diagnosed with mild HA at the age of 8 after recurrent joint bleeds. His OSA FVIII level was 13.8% and CSA FVIII level was 1.5%. He has been on emicizumab prophylaxis for 10 months without any bleeding event. Conclusion While discrepancies between assays in mild hemophilia have been widely reported, there are fewer reports on an assay discrepancy changing a diagnosis from mild to moderate HA. As such, we strongly suggest performing both OSA and CSA for the diagnosis and classification of HA especially if the PwHA has more bleeding episodes than expected. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Ankle joint distraction is a promising alternative treatment for patients with severe haemophilic ankle arthropathy.

Haemophilic ankle arthropathy (HAA) causes major morbidity. When conservative treatment fails, major surgical interventions are indicated. An alternative treatment to maintain joint mobility and postpone these interventions is desired. To gather prospective data on clinical/structural changes after ankle joint distraction (AJD) in HAA. This study includes patients with severe HAA insufficiently responding to conservative treatment. AJD was performed during 8-10weeks by use of an external frame. Questionnaires, physical examination and radiology were used to evaluate pain, function and structural changes before and 6, 12, 24 and 36months after distraction. Mixed effect models were used for analysis. This study includes eight cases (21-53years). The fixed effects estimates of the visual analogue score (0-10) improved from 7.5 at baseline to 3.4 (p=.023) 3years after distraction. The Haemophilia Activities List (HAL, 0-100) for basic/complex lower extremities functions improved from respectively 29.6 and 31.5 to 54.3 (p=.015) and 50.7 (p=.031). Joint mobility was maintained. Magnetic resonance imaging (MRI) showed thickened cartilage and reduced bone marrow oedema and subchondral cysts. Pin tract infections (n=6) were effectively treated and no adverse bleeding events occurred. At 3-year follow-up, in none of the patients the originally indicated arthrodesis was performed. This first prospective study showed that AJD in HAA results in decreased pain, improved function and decreased arthropathy-related MRI findings in the majority of patients for prolonged time. Although the study population is small and follow-up is relatively short, AJD may be promising to postpone invalidating interventions and might be a breakthrough treatment.

ADAMTS-4 as a possible distinguishing indicator between osteoarthritis and haemophilic arthropathy.

IntroductionOsteoarthritis (OA) and haemophilic arthropathy (HA) are clinically similar, but pathologically distinct conditions which result in joint pain and loss of function. Distinguishing their disease mechanisms is therefore a key step in the development of curative therapy, as opposed to current symptomatic treatments. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) 4 is a metzincin‐family member proteoglycan with known local involvement in OA pathogenesis.AimTo investigate the potential differences and discriminatory potential of ADAMTS‐4 between OA and HA patients.MethodsWe determined ADAMTS‐4 plasma concentrations by ELISA in patients with HA and OA. This pilot cross‐sectional study included N = 40 male participants equally divided across four subgroups: haemophilia patients with severe or mild HA and control subjects with severe or mild/no OA.ResultsOur study showed a striking elevation in plasma ADAMTS‐4 expression levels in HA patients as compared to OA, as well as an increase in patients with severe as compared to mild HA. By performing the binomial logistical analysis and fitting the receiver–operator curve (ROC) (cut‐off probability .5), ADAMTS‐4 had a sensitivity of 95% and specificity of 50% in discriminating between HA and OA among our study participants.ConclusionUncovering the marked differences in plasma levels of ADAMTS‐4 in patients with HA versus OA potentially sheds new light on the mechanisms of HA pathogenesis and could foster more research into the roles ADAMTS‐4 and other matrix metalloproteinases (MMPs) play in HA versus OA.

Total knee replacement for patients with severe hemophilic arthropathy in Taiwan: A nationwide population-based retrospective study.

Total knee replacement (TKR) surgery is a treatment option for advanced hemophilic arthropathy. Due to its rarity and complexity, previous reports could only demonstrate the results of single-site studies including few cases. This population-based study aimed to investigate the major epidemiological characteristics, mean consumption of coagulation factors, length of hospital stays, complications, and failure rate of primary TKR for severe hemophilia patients in Taiwan. A cohort of 996 hemophilia patients registered between 1995 and 2011 was included, and 103 primary TKRs were performed on 75 patients. Unilateral TKR was performed on 47 patients and bilateral TKRs on the remaining 28 patients, including 12 simultaneous and 16 staged surgeries. The mean age at surgery was 32.3 years (range, 17.3-55.7), and the mean follow-up duration was 77.9 months (range, 2.3-176.8). Failure was noted in 8 patients (8.5%) at mean 32.8 months (range, 2.3-95) after surgery. Four patients revealed aseptic loosening, whereas infection in 4. The 10-year prosthesis survivorship was 88.6%. For patients receiving unilateral TKR, the mean length of hospital stay was 15 days (range, 7-32). The mean cost of factor supplement was United States Dollar (USD) 43 543 with a mean 4-unit packed red blood cells transfusion (range, 0-38). The total admission cost was USD 48 326 (range, USD 4165-262 619). The prevalence of TKA for hemophilia patients was 7.5% in Taiwan. The mean hospital stay was 14 days, and the 10-year prosthesis survivorship was 88.6%. The mean daily factor usage was decreased from 235.7 units preoperatively to 202.1 units postoperatively. In comparison with the staged-bilateral TKRs, the simultaneous procedures significantly reduced the mean total cost from USD 101 923 to USD 61 587 (p = 0.023). Therefore, in terms of cost-effectiveness, bilateral simultaneous TKR is more preferable than staged procedures.

Cementless total hip arthroplasty in haemophilia patients through direct anterior approach.

Total hip arthroplasty (THA) has become the treatment of choice for patients with severe haemophilic arthropathy of the hip. However, the intraoperative and postoperative complications, including blood loss and infection, are significant concerns. Direct Anterior Approach (DAA) might be beneficial in THA of patients with haemophilia. The present study was conducted to assess outcomes of THA using DAA in patients with haemophilia. We retrospectively reviewed our joint replacement database. From January 2010 to December 2015, we had 12 patients with haemophilia who underwent 14 THAs by DAA and followed for an average of 69months. All patients were male with a mean age of 36±7years at the time of THA. The mean Harris Hip Score improved from 46 preoperatively to 89 at the final follow-up visit. One dislocation and one infection occurred. Only one patient with simultaneous bilateral THA needed a transfusion. All components were radiologically well fixed at the final follow-up visit except one acetabular loosening that needed revision. All patients were satisfied with the outcome of the surgery at the final follow-up visit. In this study, it was observed that complications of cementless THA using DAA in haemophilia patients with hip arthropathy are comparable to other surgical approaches. However, the complication of bleeding in this approach might be less.

Plasma levels of IL-1β and IL-37 in patients with severe haemophilia.

ObjectiveHaemophilia A and B are disorders caused by the lack of clotting factors VIII and IX, respectively. Repeated bleeding into the same joint leads to haemophilic arthropathy (HA). Interleukin (IL)-1β is responsible for the pro-inflammatory response and IL-37 is induced by IL-1β stimuli to have an anti-inflammatory response and prevent uncontrolled inflammation and tissue damage. Our objective was to investigate plasma levels of IL-1β and IL-37 in patients with severe haemophilia with different severities of HA.MethodsPeripheral blood samples were collected from 14 patients with severe haemophilia A and 6 with severe haemophilia B, and 18 healthy individuals. Plasma levels of IL-1β and IL-37 were detected by immunoassay, and severity of HA was evaluated using the Pettersson scoring system. Plasma levels of IL-1β and IL-37 were analysed in patients with severe haemophilia grouped by Pettersson score and in healthy individuals.ResultsPlasma levels of IL-1β and IL-37 were significantly higher in patients with severe haemophilia compared with healthy individuals and significantly lower in those with moderate to severe HA than in those with no or mild HA.ConclusionsPlasma levels of IL-1β and IL-37 may be useful to track HA progression in patients with severe haemophilia.

The biomechanical behaviour of ankle and foot joints during walking with shoes in patients with haemophilia.

Patients with haemophilia (PwH) often prefer shod walking over barefoot walking as footwear offers ankle joint stability and comfort during gait. Yet, the biomechanical mechanisms contributing to the latter remain poorly understood. To explore the effect of shoes on the biomechanical functioning of the ankle and foot complex in PwH with and without haemophilic ankle arthropathy and to determine the amount of ankle joint loading during shod walking. We analysed data of PwH without haemophilic ankle arthropathy (n=5) and PwH with severe haemophilic ankle arthropathy (n=17) and a control group (n=17). During 3D gait analysis, a four-segment kinetic foot model was used to calculate kinematic and kinetic parameters of the ankle, Chopart, Lisfranc and first metatarsophalangeal (MTP 1) joints during both barefoot and shod walking. We found a significantly greater ankle joint power generation during shod walking compared to barefoot walking in PwH with severe haemophilic ankle arthropathy (P<.001). Chopart joint biomechanics were significantly lowered in all three groups during shod walking compared to barefoot walking. During shod walking, the ankle joint load was significantly lowered in both PwH groups (P=.039 and P=.002), but not in the control group (P=.952). Explorations in this study uncover a tendency that shoes alter the biomechanical functioning of the ankle and foot complex in PwH and simultaneously lower the ankle joint load during walking.

Surgical approaches to hemophilic arthropathy.

: The role of the orthopedic surgeon is to use invasive and/or surgical methods to treat the musculoskeletal disorders suffered by persons with hemophilia, always within the context of a multidisciplinary team. Muscle hematomas must be diagnosed as early as possible and be subjected to continuous treatment until full resolution, as they are associated with the risk of severe complications (compartment syndromes and pseudotumors). Arthrocentesis (extraction of intra-articular blood) is recommended in cases of acute and profuse hemarthrosis. Synovectomy is mandatory in the case of synovitis. Radiosynovectomy plays a key role as it has been shown to reduce bleeding by 65%. Our department uses Yttrium-90 in knees and Rhenium-186 in elbows and ankles. Radiosynovectomy is our treatment of choice for synovitis whereas arthroscopic synovectomy is resorted to as second-line treatment. Total knee replacement (TKR) has shown itself to be effective for treating severe hemophilic arthropathy, although the infection risk in patients with hemophilia is higher than in patients with osteoarthritis (1-2 vs. 7%).

TNF-α/TNF-R System May Represent a Crucial Mediator of Proliferative Synovitis in Hemophilia A.

Hemophilic arthropathy (HA) typically begins with proliferative synovitis that shares some similarities with inflammatory arthritides, in which the proinflammatory cytokine tumor necrosis factor (TNF)-α has a crucial pathogenetic role. Inappropriate release of TNF-α was shown to contribute to arthropathy development following intra-articular bleeding in hemophilic mice. Here, we were interested in determining whether systemic levels of TNF-α and synovial tissue expression of the TNF-α/TNF receptor (TNF-R) system could be increased and related to joint damage in hemophilia A patients with severe HA. Serum levels of TNF-α measured by quantitative enzyme-linked immunosorbent assay (ELISA) were significantly increased in HA patients (n = 67) compared to healthy controls (n = 20). In HA patients, elevated TNF-α levels were significantly associated with the number of hemarthroses, the grade of synovial hypertrophy, and both the clinical World Federation of Hemophilia score and ultrasound score. The expression of TNF-α, TNF-R1, and TNF-R2 was strongly increased in HA synovium (n = 10) compared to the non-inflamed osteoarthritis control synovium (n = 8), as assessed by both immunohistochemistry and Western blotting. Increased protein levels of TNF-α, TNF-R1, and TNF-R2 were retained in vitro by HA fibroblast-like synoviocytes (n = 6) with respect to osteoarthritis control fibroblast-like synoviocytes (n = 6). Stimulation with TNF-α resulted in a significant increase in HA fibroblast-like synoviocyte proliferation quantified by the water-soluble tetrazolium (WST)-1 assay, while it had no relevant effect on osteoarthritis fibroblast-like synoviocytes. Quantification of active/cleaved caspase-3 by ELISA demonstrated that TNF-α did not induce apoptosis either in HA or in osteoarthritis fibroblast-like synoviocytes. The TNF-α/TNF-R system may represent a crucial mediator of proliferative synovitis and, therefore, a new attractive target for the prevention and treatment of joint damage in HA patients. Our findings provide the groundwork for further clinical investigation of anti-TNF-α therapeutic feasibility in hemophiliacs.

Constrained Rotating Hinge Prostheses in Severe Haemophilic Knee Osteoarthritis

The purpose of this experimental study is to present the design and biomechanical characteristics of cemented total knee prostheses type rotating-hinge RT-PLUS® (Smith and Nephew), as well as to evaluate their use in severe haemophilic knee arthropathy with major bone damage, ligamentous lesions, axial deviations and muscle retractions. We retrospectively evaluated 5 patients with severe haemophilic arthropathy with an average age of 48.5years. The functional results are good, with a significant improvement of range of motion (ROM) and pain relief resulting in a much better life quality. We did not have any stem loosening or any other complications except 2 wound healing problems which were treated successfully. The authors recommend this type of arthroplasty in severe haemophilic knee arthropathy or in any primary knee osteoarthritis with severe bone loss or any kind of ligamentous lesions.

Observational Study of Real-World Factor Utilization and Health Outcomes in Patients with Hemophilia in Canada

Observational Study of Real-World Factor Utilization and Health Outcomes in Patients with Hemophilia in Canada

Joint lavage followed by intra-articular injection of hyaluronic acid and/or corticosteroids in patients with severe hemophilic arthropathy of the knee: Is this intervention really effective?

ABSTRACTIntroduction: The aim of this review is to explore the scientific rationale and evidence for a potential benefit of joint lavage followed by intra-articular injection of hyaluronic acid and/or corticosteroids in patients with severe hemophilic arthropathy of the knee (SHAK).Areas covered: This article is a narrative review of the evidence for potential benefits of joint lavage followed by intra-articular injection of hyaluronic acid and corticosteroids in SHAK compared with osteoarthritis of the knee in non-hemophilia patients.Expert commentary: Although some reports on hemophilic arthropathy with a low-grade of evidence seem to indicate a benefit of joint lavage followed by intra-articular injection of hyaluronic acid and/or corticosteroids in patients with SHAK, the short-lived improvements afforded by hyaluronic acid, and the doubtful benefits of corticosteroids and joint lavage in hemophilia, do not warrant their use in hemophilic patients. The scientific rationale of these procedures is poor and they are not recommended.

Total elbow arthroplasty in haemophilia.

Advanced haemophilic arthropathy of the elbow can be a devastating manifestation of severe haemophilia with significant implications for activities of daily living. To summarize the currently available data on total elbow arthroplasty (TEA) for haemophilic arthropathy of the elbow, to draw comparisons to TEA for other indications, and to outline some considerations regarding TEA in this unique population. A narrative review of the literature has been performed. The scant data regarding outcomes of TEA for haemophilic arthropathy are limited to small case series and case reports. A review of the available literature shows that, while pain relief and patient satisfaction are promising, variable outcomes with significant complications and infection rates may discourage routine use of TEA for haemophilic arthropathy of the elbow. While patients with severe haemophilic arthropathy of the elbow are likely to make gains in terms of pain control and range of motion following TEA, there are insufficient data to routinely recommend its use. Complication and infection rates are concerning, and the lack of survival analysis data makes it difficult to quantify the benefit to the patient in light of the risks and resources involved in the procedure.