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Objective: T2-relaxometry could differentiate between physiological and haemorrhagic joint effusion (≥ 5% blood) in vitro. Are quantitative T2-relaxation time measurements of synovial fluid feasible and reproducible in vivo in clinically bleed-free joints of men with haemophilia?, Materials and Methods: In this cross-sectional study, we measured T2-relaxation times of synovial fluid in clinically bleed-free ankles, knees or elbows of men with severe haemophilia A using a T2-mapping sequence (duration ≤ 7 min) at 3 Tesla MRI. Manual and circular regions of interest (ROI) were drawn in the synovial fluid of each joint by two independent observers to measure T2-relaxation times. Measurement feasibility was expressed as the success rate of the measurements by both observers. The interobserver and intraobserver reproducibility of the measurements were evaluated by the intraclass correlation coefficient of absolute agreement (ICC) and the limits of agreement (LoA) from Bland Altman analysis., Results: We evaluated 39 clinically bleed-free joints (11 ankles, 12 knees, 16 elbows) of 39 men (median age, 24 years; range 17-33) with severe haemophilia A. The success rate of the T2-measurements was ≥ 90%. Interobserver reliability was good to excellent (manual ROI: ICC = 0.92, 95% CI 0.76-0.97; circular ROI: ICC = 0.82, 95% CI 0.66-0.91) and interobserver agreement was adequate (manual ROI: LoA = 71 ms; circular ROI: LoA = 146 ms). Intraobserver reliability was good to excellent (manual ROI: ICC = 0.78, 95% CI - 0.06-0.94; circular RO: ICC = 0.99, 95% CI 0.98-0.99) and intraobserver agreement was good (manual ROI: LoA = 63 ms; circular ROI: LoA = 41 ms)., Conclusion: T2-relaxometry of synovial fluid in haemophilia patients is feasible with good interobserver and intraobserver reproducibility., (© 2024. The Author(s).)

Introduction: Early diagnosis of joint damage is pivotal in haemophilia to prevent the occurrence and progression of haemophilic arthropathy thus providing optimal personalised management. The haemophilia joint health score version 2.1 (HJHS) is based on a physical examination of the mainly affected joints. Musculoskeletal ultrasound has demonstrated the capability to detect early changes in terms of synovitis and osteochondral damage. The haemophilia early detection with ultrasound (HEAD-US) score has been proposed as a simple and reliable evaluation tool., Aim: This study aims to investigate the correlation between the HJHS and the HEAD-US scores performed by two independent operators (physical therapist and musculoskeletal ultrasound expert) for the evaluation of the joint health status of patients with haemophilia., Methods: Consecutive adult patients independent of the severity degree were included. Elbows, knees and ankles were evaluated by a physical therapist by HJHS and by a musculoskeletal ultrasound expert following the HEAD-US protocol., Results: We observed a good positive correlation between HJHS and HEAD-US (Spearman's rho 0.72). The main discrepancy in conceptually similar domains was found between the HJHS swelling and the HEAD-US synovitis (rho 0.17), as ultrasound was able to detect even mild synovitis when HJHS swelling was scored 0 in up to 40% of cases., Conclusions: The HJHS and HEAD-US correlate well even when performed by two independent operators. Musculoskeletal ultrasound is particularly useful for the early detection of synovitis. The routine assessment of both scores helps clinicians define the stage and extension of joint involvement and set up a personalised treatment., (© 2024 The Authors. Haemophilia published by John Wiley & Sons Ltd.)

Introduction/aim: To evaluate whether patients with haemophilia (PwH) can be enabled to perform ultrasonography (US) of their knees without supervision according to the Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) protocol and whether they would be able to recognize pathologies., Methods: Five PwH (mean age 29.6 years, range 20-48 years) were taught the use of a portable US device and the HEAD-US protocol. Subsequently, the patients performed US unsupervised at home three times a week for a total of 6 weeks with a reteaching after 2 weeks. All images were checked for mapping of the landmarks defined in the HEAD-US protocol by a radiologist. In a final test after the completion of the self-sonography period, participants were asked to identify scanning plane and potential pathology from US images of other PwH., Results: On the images of the self-performed scans, 82.7% of the possible anatomic landmarks could be identified and 67.5% of the requested images were unobjectionable, depicting 100% of the required landmarks. There was a highly significant improvement in image quality following reteaching after 2 weeks (74.80 ± 36.88% vs. 88.31 ± 19.87%, p < .001). In the final test, the participants identified the right scanning plane in 85.0% and they correctly identified pathology in 90.0% of images., Conclusion: Appropriately trained PwH can perform the HEAD-US protocol of their knee with high quality and are capable to identify pathologic findings on these standardized images. Asynchronous tele-sonography could enable early therapy adjustment and thereby possibly reduce costs., (© 2024 The Author(s). Haemophilia published by John Wiley & Sons Ltd.)

Objectives: This study aimed to assess the reliability of the Hemophilia Early Arthropathy Detection with Ultrasound in China (HEAD-US-C) scale for the knees of severe hemophilia A (SHA) patients and to determine its diagnostic accuracy for assessments of knee-joint lesions in comparison with magnetic resonance imaging (MRI)., Methods: We collected data from 32 knee joints of 21 patients diagnosed with SHA. The knees were evaluated based on the HEAD-US-C scale and the results were compared with the International Prevention Study Group (IPSG) scale. The HEAD-US-C scale was applied independently by two trained ultrasonographers blinded to the MRI results. The IPSG scale was applied independently by two radiologists blinded to the clinical data and ultrasound (US) results., Results: The IPSG and HEAD-US-C scales exhibited good to excellent inter-rater reliability. Additionally, there was good to excellent agreement between the US and MRI results for the detection of knee lesions in SHA patients. The sensitivities of US for joint effusion, synovial hyperplasia, cartilage loss, and bone-surface irregularities in the knees of patients were 92.59, 100, 95.45, and 87.50%, respectively. The HEAD-US-C scale was positively correlated with the IPSG scale., Conclusions: US is important for evaluating knee lesions in patients with SHA and may potentially replace MRI., (© 2023 American Institute of Ultrasound in Medicine.)

Objectives: This study aimed to assess the morphological differences in the articular disc (AD) between hemophilic patients and healthy individuals of the control group for further association with signs and symptoms., Methods: Fourteen severe hemophilic patients had their AD evaluated by magnetic resonance imaging (MRI). The morphological findings were compared to those of a control group consisting of 14 healthy individuals. MRI was used to evaluate all the components of the temporomandibular (TMJ), including the AD, resulting in sequential T1-weighted parasagittal images. All the images were acquired with teeth in maximum intercuspation position., Results: Morphological alterations showed significant statistical differences (P-value = 0.0068), whereas no statistical differences were found in the other variables, including TMJ pain, headache, bruxism and mouth opening limitation. In the group of non-hemophilic individuals, only two (14.29%) presented AD with non-biconcave features, whereas in the group of hemophilic patients, nine (64.29%) presented AD with a morphology other than biconcave., Conclusions: In patients with severe hemophilia, there seems to be a pattern of morphological alterations in the articular disc over time. The standard biconcave morphology of AD tends to change into other ones, particularly biplanar, hemiconvex and folded., (© 2023. The Author(s) under exclusive licence to Japanese Society for Oral and Maxillofacial Radiology.)

Objectives: The Joint tissue Activity and Damage Exam (JADE) is a point-of-care (POC) musculoskeletal ultrasound (MSKUS) protocol for non-radiologists to evaluate hemophilic arthopathy. Our aim was to determine the consistency of cross-sectional analyses of direct tissue measurements (JADE protocol) and clinical Hemophilia Joint Health Score [HJHS] and functional joint assessments (arc) at three clinic visits., Methods: We prospectively studied adults (n = 44) with hemophilia (A or B) of any severity and arthropathy at 3 North American sites. We assessed HJHS, total arc, and JADE parameters (bilateral elbows, ankles, and knees) at study entry, at ≈12-18 months, and at ≈24-36 months, and used MSKUS to evaluate painful episodes between study visits. JADE measurements included osteochondral alterations, cartilage thickness, and soft tissue expansion at sentinel positions. Associations between joint HJHS and total arc with each JADE variable were examined with random intercept models., Results: At each visit increasing HJHS and decreasing total arc were associated in the expected direction with increasing length of OAs and soft tissue expansion in all joints, and decreasing cartilage thickness in the knee. However, HJHS associations with cartilage thickness were U-shaped for elbow and ankle (i.e. cartilage thinning and thickening). Associations between total arc and cartilage thickness followed a similar curve. (Near) normal levels of both joint parameters (HJHS and total arc) were associated with normal ranges of cartilage thickness. JADE views were also helpful to detect hemarthrosis in association with joint pains., Conclusions: POC MSKUS applying direct tissue measurements using the JADE protocol provided reproducible cross-sectional associations with joint health outcomes on three visits. These findings advance protocol validation and enable iterative adaptations resulting in JADE protocol version 2., (© 2023. The Author(s).)

Background: Teleguidance on portable devices opens the possibility of joint self-imaging in persons with hemophilia (PWH)., Aims: Determine the feasibility of patient self-imaging with/without teleguidance., Methods: Adult PWH received ultrasound teaching including 11 views for hemarthrosis detection in ankles, elbows, and knees. The patients acquired five randomly selected views with the Butterfly/IQ probe without assistance at 2, 6-8 weeks, and 3-4 months later, followed by teleguidance. Image acquisition was timed, patients identified anatomic landmarks, and image quality was graded. Questionnaires assessed the imaging experience. Hemophilia Joint Health Score (HJHS) indicated arthropathy status., Results: Of 132 PWH, 10 (median age 52 years) opted for study inclusion. Most had severe Hemophilia A, were white/non-Hispanic, with at least a high school degree and, overall, similar to the other 122 PWH. At 2 and 6 weeks after training, ~80% images were acquired correctly compared with 53% at 12 weeks. Accuracy of landmark recognition was ~55%. With teleguidance, all images were acquired correctly, with near-perfect image quality (P ≤ .01 compared with the 3-4 month time point). Median HJHS of scanned joints was 11.5 at each time point, demonstrating a similar spectrum of arthropathic changes. Median time of image acquisition was fast, and similar with or without teleguidance (median 01:04 [mm:ss] vs median 01:02), but differed slightly between arthropathic and non-arthropathic joints. Study participants and the imaging facilitator rated that it was easy to navigate mobile technology and acquire images with teleguidance., Conclusion: Mobile ultrasound with teleguidance for joint self-imaging is feasible and warrants further exploration., (© 2022 The Authors. Journal of Ultrasound in Medicine published by Wiley Periodicals LLC on behalf of American Institute of Ultrasound in Medicine.)

Background: The use of musculoskeletal ultrasound (MSKUS) for point-of-care (POC) evaluation of hemophilic arthropathy is growing rapidly. However, the extent to which MSKUS influences clinical treatment decisions is unknown., Methods: We conducted a three-year, prospective, multi-center study at three hemophilia treatment centers in the United States to evaluate the utilization of POC-MSKUS for routine clinical decision-making in adult persons with hemophilic arthropathy. Bilateral elbows, knees and ankles were assessed clinically [Hemophilia Joint Health Score (HJHS)] and with POC-MSKUS by the Joint Tissue Activity and Damage Exam (JADE) protocol at baseline and approximately annually for two additional times. Treatment decisions, including physical therapy (PT) and "medical" (joint injections/aspirations, referrals to orthopedics, changes/adjustments of hemostatic plans, and use of oral anti-inflammatory medications) were recorded in relation to POC-MSKUS., Results: Forty-four persons [median age 37 years (IQR 29, 51)], mostly with severe Hemophilia A on clotting factor prophylaxis, completed 129 visits, yielding 792 joint exams by POC-MSKUS and HJHS [median at baseline 27 (IQR 18, 42)] over a median follow up of 584 days (range: 363 to 1072). Among 157 management decisions, 70% were related to PT plans (n = 110) and 30% were "medical". Point-of-care MSKUS influenced 47/110 (43%) PT plans, mostly informing treatment of specific arthropathic joints (45/47 plans) in patients with high HJHS. Physical therapy plans influenced by POC-MSKUS directed more manual therapy/therapeutic exercises, while plans based on physical exam were focused more on global exercises and wellness. Treatment decisions were mostly based on the identification of specific musculoskeletal abnormalities visualized by POC-MSKUS. Of note 20/47 (43%) POC-MSKUS plans included de-escalation strategies, thereby reducing exercise intensity, mostly for joint instability and subclinical hemarthroses. Point-of-care MSKUS also informed 68% (32/47) of "medical" decisions, surprisingly mostly for injections/aspirations and referrals to orthopedics, and not for adjustments of hemostatic treatment. Although not formally studied, ultrasound images were used frequently for patient education., Conclusion: Routine joint evaluations with POC-MSKUS resulted in few changes regarding medical management decisions but had a profound effect on the formulation of PT plans. Based on these findings, new studies are essential to determine the benefit of MSKUS-informed management plans on joint health outcomes., (© 2022. The Author(s).)

Background: Ultrasound (US) has been proven to be reliable in the assessment of early haemophilic arthropathy in the adult haemophilic population, however few studies so far focused on the reliability of US specifically in the paediatric haemophilic population. We were interested if the changing appearance of the growing bone hinders the ultrasonographic evaluation of the pathologic processes caused by haemophilic arthropathy. The aim of the study was to assess the reliability of US for evaluation of haemophilic arthropathy in children in comparison to magnetic resonance imaging (MRI)., Patients and Methods: The study included all children aged 6 years or more with severe haemophilia in the country (n = 10). We assessed their elbows, knees, and ankles bilaterally by US and compared the results to the MRI as the reference standard. Pearson correlation coefficient (r) was used to analyse correlation., Results: The correlation with MRI for the US for the total score was excellent for all joints (r = 0.849 for the elbows, r = 1 for knees, r = 0.842 for ankles). The correlation of scores for specific joint components showed fair, moderate, or excellent correlation for all joint components in all joints. The correlation was the lowest for the evaluation of cartilage and bone in the ankles (r = 0.546 and r = 0.478) and bone in the elbows (r = 0.499)., Conclusions: Our study proved that US using the HEAD-US method performed by paediatric radiologists is a reliable tool for detection and quantification of haemophilic arthropathy in children in comparison to MRI., (© 2022 Domen Plut, Barbara Faganel Kotnik, Luka Pusnik, Peter Slak, Ziga Snoj, Vladka Salapura, published by Sciendo.)

Haemophilia is a common hereditary cause of bleeding diathesis and the musculoskeletal system is frequently affected. Repeated episodes of haemarthrosis initiate a cascade towards haemophilic arthropathy, a disabling and deforming joint disease with both degenerative and inflammatory features, which include articular cartilage loss, bone erosions, and synovitis. Haemophilic pseudotumour and intra-muscular haematoma make up the remainder of the musculoskeletal manifestations of this systemic condition. Radiological assessment is vital in the assessment and follow-up of these haemophilic complications and MRI is the reference standard. This article summarises the radiological findings relevant to the diagnosis and monitoring of this complex patient group., (Crown Copyright © 2022. Published by Elsevier Ltd. All rights reserved.)

Hemophilia is characterized by bleeding diathesis, primarily affecting the joints. Prophylactic use of missing factor aims at limiting the number of bleeds and, in the long term, the risk of permanent joint damage. However, standard prophylactic regimens are usually applied empirically, not adjusting for variations in bleeding phenotype or drug metabolism. Aim of the present study was to evaluate the need for individualizing prophylaxis, with guidance of pharmacokinetic (PK) studies and joint ultrasound in a setting of everyday clinical practice. To evaluate adequacy of applied regimens, joint status was assessed using the Hemophilia Joint Health Score as well as ultrasound imaging, while PK studies were performed using the Web-Accessible Population Pharmacokinetic Service-Hemophilia. Imaging results were consistent with early joint damage in a large proportion of pediatric patients, whereas PK measures were indicative of inadequate prophylaxis in many cases-despite the limited number of bleeds reported by patients. The study revealed the need for prophylaxis adjustment in the majority of patients. Real world data confirm that traditional prophylaxis is often unable to achieve therapeutic goals, while an individualized approach, guided by the use of novel modalities, may be of great benefit to young hemophilia patients., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Abnormal epiphyseal growth plate development of the proximal tibia in hemophilia patients leads to notable morphological changes in the mature knee joint. This study aimed to compare the morphological characteristics of tibial component placement cut surface in patients with hemophilic arthritis (HA) and osteoarthritis (OA) and to determine the tibial component rotational alignment axis' best position for HA patients., Methods: Preoperative computed tomography scans of 40 OA and 40 HA patients who underwent total knee arthroplasty were evaluated using a three-dimensional (3D) software. The tibial component's placement morphological parameters were measured. The tibial component's rotational mismatch angles were evaluated, and the most appropriate 0°AP axis position for HA patients was investigated., Results: In the two groups, the morphology was significantly different in some of the parameters (p < 0.05). The tibial component rotational mismatch angles were significantly different between both groups (p < 0.05). The medial 9.26° of the medial 1/3 of the patellar tendon was the point through which 0°AP axis passed for the HA patients. Similarly, the medial 13.02° of the medial 1/3 of the tibial tubercle was also the point through which the 0°AP axis passed., Conclusions: The ratio of the anteroposterior length to the geometric transverse length of the placement section of the tibial component in HA patients was smaller than that in OA patients. The medial 9.26° of the medial 1/3 of the patellar tendon or the medial 13.02° of the medial 1/3 of the tibial tubercle seem to be an ideal reference position of the rotational alignment axis of the tibial component for HA patients., (© 2022. The Author(s).)

Objective: Contrast-enhanced ultrasound (CEUS) is advantageous for evaluating microcirculation, and has been applied to assess arthritis in previous studies. However, CEUS examinations have not been studied for hemophilia arthritis. Hemophilia arthritis is different from other arthritis, because it is induced by spontaneous joint bleeding. Hence, CEUS may have special value in evaluating hemophilia arthritis. The present study assessed the value of CEUS in evaluating synovial hypertrophy and predicting recurrent joint bleeding in severe hemophilia A patients., Methods: From August 2016 to January 2017, 81 severe hemophilia A patients, who were referred to our hospital for ultrasound joint assessment with conventional ultrasound, were enrolled. Among these 81 patients, 46 patients consented for CEUS examinations on the same day., Results: Compared to color Doppler flow imaging (CDFI), four more joints presented with a blood flow signal under CEUS mode. In addition, the synovial hypertrophy measured by CEUS was thicker than that measured by conventional ultrasound. The ultrasound scores (including the total grey-scale ultrasound score, joint effusion/hemarthrosis, synovial hypertrophy, CDFI semi-quantitative score, and CEUS semi-quantitative score) were significantly higher in the joint bleeding group than in the no joint bleeding group (P<0.05). Furthermore, these ultrasound scores were positively correlated with the joint bleeding frequency, and had the highest correlation with the CEUS score (r=0.620, P<0.05)., Conclusion: CEUS can more accurately assess the degree of synovial hypertrophy and vascularization, and diagnose synovitis, when compared to conventional ultrasound. In addition, CEUS appears to be essential for evaluating the possibility of recurrent joint bleeding, and providing more reliable evidence for individualized treatment., (© 2022. Huazhong University of Science and Technology.)

Background: Joint ultrasound examination using the HEAD-US method in the detection of early arthropathy is poorly studied in our country., Objective: To compare the clinical and ultrasound evaluation of the joints in haemophilia., Method: Longitudinal, prospective and descriptive study with paediatric patients with haemophilia A and B evaluated with the HJHS 2.1 scale and ultrasound with a linear transducer of 8 to 12 MHz. Elbows, knees and ankles joints were evaluated bilaterally, with HEAD-US protocol., Results: 69 paediatric patients were included of which 48 with severe haemophilia A (weight: 40.1 kg). On the HJHS scale, a greater involvement was observed in the left knee (0.49), and less in the right ankle (0.05). With the HEAD-US scale, the most affected was the right knee (0.78). There is a significant relationship in the involvement of the right knee evaluated with the HEAD-US scale in the presence of inhibitor., Conclusions: Weight above the 50 th percentile is an independent risk factor for joint bleeding complications, while age and type of haemophilia do not appear to be related. The HEAD-US method is a useful and accessible tool for early detection of arthropathy and hemarthrosis., (Copyright: © 2022 Permanyer.)

Objectives: Children with hemophilia have the usual childhood risk of falls and head trauma. Head computed tomographies (HCTs) are fast, detailed, and readily available, but increased radiation exposure in the pediatric population is now recognized as causing increased brain malignancy. By examining the incidence of intracranial cerebral hemorrhage in this population, we will be able to weigh risks and benefits of HCT use more accurately., Methods: Using a retrospective chart review, we examined past medical records of pediatric patients, aged 0 to 15 years, with hemophilia presenting to 1 academic medical center. Primary outcomes included number of head CTs ordered, total and per patient over the years studied, and the incidence of positive findings, as defined by presence of blood products as documented by radiologist final read/interpretation., Results: The mean number of head CTs per child was 2.5 (range, 1-10). None of the HCT scans were read as intracranial cerebral hemorrhage, and none of the patients had findings that lead to neurosurgical intervention. In a sensitivity analysis, applying Pediatric Emergency Care Applied Research Network head injury criteria, 11 HCT scans would be ordered for a reduction of 80 HCTs, or a decrease of 2 HCT scans per child. No incidence of intracranial cerebral hemorrhage would have been missed., Conclusions: Our findings suggest that in the child with hemophilia and a history of minor head trauma, exposure to the radiation of a HCT based on the diagnosis of hemophilia alone may not be necessary but that imaging decisions need to be made in conjunction with clinical examination findings and neurologic status., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Early detection of bleeding into a joint is crucial in patients with haemophilia. This study was designed to evaluate the sensitivity of ultrasonography (USG) and magnetic resonance imaging (MRI) to detect the presence of blood in small concentrations in a simulated model to mimic joint bleeding., Materials and Methods: Different concentrations of blood in plasma, varying from 0.1% to 45%, were collected in 10-ml plastic syringes and imaged using 12 and 18 MHz USG transducers and with 1.5T and 3T MRI scanners, at different intervals of time following dilution. The images were scored for the presence of blood by four experienced radiologists who were blinded to the concentration of blood., Results: Within the first 2 h, the 18 MHz transducer was able to detect blood consistently up to 0.5%, whereas the 12 MHz transducer could consistently identify blood up to 1.4%. After the first 12 h, both transducers were able to detect blood up to 0.5% concentration. However, at concentrations below 0.5%, there was discordance in the ability to detect blood, with both transducers. There was no correlation between the signal intensities of MRI images and concentration of blood, at different time intervals, irrespective of the magnetic field strength., Conclusions: Detection of blood using the USG is dependent on variables such as the concentration of blood, frequency of the transducer used and timing of the imaging. As the concentration of blood decreases below 0.5%, the discordance between the observers increases, implying that the detection limit of USG affects its reliability at lower concentrations of blood. Caution is urged while interpreting USG imaging studies for the detection of blood in symptomatic joints., (© 2021 John Wiley & Sons Ltd.)

: In hemophilic patients methods are needed to better diagnose joint damage early, so that treatments can be adjusted to slow the progression of hemophilic arthropathy. The aim of this study is to investigate the relationship between the Hemophilia Joint Health Score version 2.1 (HJHS 2.1) and hemophilia early arthropathy detection with ultrasound (HEAD-US) scales, as well as each of their individual items, to better understand the value each provides on the joint condition of patients with hemophilia. The study included data from patients with hemophilia older than 16 years of age, who attended a routine check-up. HJHS 2.1 and HEAD-US assessments were performed on the elbows, knees and ankles. We studied the correlations and agreements between the two scales and analyzed the relationship between the various items of the HJHS 2.1 (inflammation, duration, atrophy, crepitation, flexion deficit, extension deficit, pain, strength, gait) and HEAD-US (synovitis, cartilage and bone). The study included 203 joints from 66 patients with hemophilia (mean age, 34 years). We found a good correlation between the two scales (r = 0.717). However, HJHS 2.1 revealed only 54% of the cases with synovitis and 75% of the cases with osteochondral damage. HEAD-US detected several relevant physical and functional aspects in less than 53% of the cases. HJHS 2.1 and HEAD-US provide complementary data on joint disease in adults with hemophilia; both assessments should therefore, be made available. HEAD-US presented the added value of detecting early joint changes (synovitis and osteochondral damage), while HJHS 2.1 showed the added value of detecting relevant physical and functional changes.

Background: Certain hemophilia patients are unable to cooperate with or afford magnetic resonance imaging (MRI) examinations. The purpose of our study was to explore the value of multislice spiral computed tomography (MSCT) in evaluating hemophilic arthropathy (HA)., Methods: Thirty-eight patients with 73 joints of HA were consecutively selected from January 2016 to May 2018 for this prospective study. All 73 joints were examined by X-ray, CT, and MRI within 2 days. The MRI scores of the joints were determined by the International Prophylaxis Study Group (IPSG) standard. The CT findings were quantified according to the IPSG standard, except for cartilage injury, which was quantified by joint space narrowing using the X-ray Pettersson score. The CT and MRI scores were compared by the paired Wilcoxon signed-rank test. The correlations between the CT score of joint space narrowing and MRI score of cartilage injury and the total CT and MRI scores were analyzed by Spearman rank correlation. The kappa test was used to compare the consistency of CT and MRI scores., Results: MRI was superior to CT based on the scores for small amount of effusion (P < 0.05), synovial hypertrophy and hemosiderin deposition in the mild groups (P < 0.05). The CT and MRI scores were not significantly different for moderate and massive effusion, synovial hypertrophy, and hemosiderin deposition in the moderate and severe groups, bone erosion or cystic changes (P > 0.05), and there was a high degree of consistency between the two scores (kappa > 0.81). The consistency between the Pettersson scores of joint space narrowing on CT and the IPSG scores of cartilage injury on MRI was high (kappa = 0. 774, P < 0.05)., Conclusion: The image scores of MSCT are generally consistent with MRI except for mild synovitis, which can be used as an alternative for the evaluation of HA.

This single-institution cross-sectional study aimed to grasp the prevalence and features of neurocognitive dysfunction in HIV-infected hemophilia patients in Japan. We conducted neuropsychological tests and medical examinations in 56 HIV-infected hemophilia patients who received outpatient treatment at the AIDS Clinical Center, National Center for Global Health and Medicine. A total of 388 HIV-infected non-hemophilia patients who received outpatient treatment at the same institution were included as a control group. To investigate sites responsible for neurocognitive dysfunction in HIV-infected hemophilia patients using brain FDG-PET/CT scans, the accumulation of FDG in each brain region was compared. Approximately 50% of HIV-infected hemophilia patients had neurocognitive dysfunction. The prevalence of asymptomatic neurocognitive impairment was high (34%). Neurocognitive dysfunction was associated with educational level in HIV-infected hemophilia patients. In the symptomatic group, hemophilic arthropathy and history of cerebrovascular disorders were associated with neurocognitive dysfunction. Left temporal lobe function was reduced in the symptomatic group., Competing Interests: The authors have declared that no competing interests exist.

Magnetic resonance imaging (MRI) is considered as the reference standard to assess early joint changes in hemophilia. However, the clinical relevance of MRI findings is still unknown. The aim of this prospective study was to assess the predictive value of MRI for 5-year joint bleeding and progression of arthropathy in patients with hemophilia. Both knees and ankles of patients with hemophilia and absent or limited arthropathy on radiographs were assessed by using MRI and radiographs. MRI scans were scored according to the International Prophylaxis Study Group MRI score for hemophilic arthropathy. Patients were followed up for 5 years, including assessment of joint bleeding and repeated radiographic assessment. Associations between baseline MRI findings with 5-year bleeding and progression of arthropathy were expressed as odds ratios (OR), adjusted for severity of disease and joint bleeding history. Baseline assessment included 104 joints of 26 patients with hemophilia (median age, 21 years). Four ankles with severe joint changes were excluded. Follow-up was available for 96 (92%) of 104 joints. During 5 years of follow-up, bleeding was reported for 36% of joints. Five-year bleeding was significantly increased in joints with synovial hypertrophy at 80% vs 27% in joints without synovial hypertrophy (OR, 10.1; 95% confidence interval, 3.4-31.3). In joints with normal baseline radiographs, any osteochondral or synovial changes on MRI were associated with radiographic changes 5 years later (positive predictive value, 75%; negative predictive value, 98%). Joints with synovial hypertrophy on MRI had a significantly higher chance of 5-year bleeding. All MRI changes, except effusion, were strong predictors for development of arthropathy on radiographs., (© 2020 by The American Society of Hematology.)

Background: Retroclival hematomas are a rare entity and may occur in 3 compartments, namely the epidural, subdural, and subarachnoid spaces. They are frequently secondary to trauma. Hemophilia is a clinical syndrome affecting usually men and characterized by the inherited tendency to bleed excessively after slight injury. Hemophilia is caused by a specific defect of coagulation factor VIII. The main concern associated with the disease is bleeding, especially after trauma and surgeries. The most serious site of bleeding is the central nervous system., Case Presentation: An 11-year-old boy diagnosed with hemophilia presented after sustaining a fall. On arrival to the emergency department, his vitals where within normal range and he was fully conscious. Neurologic examination was significant for bilateral abducens nerve palsy; the rest of the examination was unremarkable. Imaging studies with computed tomography (CT) scan and brain magnetic resonance imaging showed subacute retroclival subdural hemorrhage with left cerebellar and upper cervical spine extension. Follow-up imaging with CT scan showed progressive resolution of the hematoma, and the patient had a stable clinical course while receiving factor VII replacement., Conclusions: Retroclival subdural hematomas are rare and may present either spontaneously or after trauma. Conservative treatment is the usual course of treatment. Patients with hemophilia A are under a constant threat from bleeding, either spontaneous or after trivial injury. The most common cause of death in this patient population is intracranial hemorrhage. The most important aspect of intracranial hematoma management is the early replacement therapy of deficient coagulation factors in patients with hemophilia., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Aim: We previously reported the outcome of chromic phosphate-32( 32 P) colloid synoviorthesis in 53 haemophilic patients with an average follow-up of 31 months. The purpose of the present study was the long-term follow-up of the same cohort on both clinical and radiographic features., Materials: Nine patients failed to attend the recall appointment. The mean follow-up for the remaining 44 patients (52 procedures) was 15 years (range, 14.6-15.5). The mean age at the time of reassessment was 31 years (range, 18-43)., Results: The haemarthrosis frequency was not statistically significant at the latest follow-up years compared with 31 months (0.8 vs 0.4 per week, P = .3). There was no significant change in the clinical severity of haemophilic arthropathy (P = .5). Most of the treated joints still are in stage III of Fernandez-Palazzi and Caviglia classification. There was a trend towards the radiologic deterioration of arthritis with nearly 50% of patients at Arnold-Hilgartner Stage V. 13% of patients underwent a total knee arthroplasty (TKA). The age at which the initial radiosynovectomy was performed was significantly higher in patients who had a TKA than those who had not (22 vs 15 years, P < .002)., Conclusion: The bleeding control effect of 32P on the target joint remains over time; however, it did not appear to halt the progression of radiographic changes in haemophiliacs. It could delay the need for TKA if it performs at the right time., (© 2019 John Wiley & Sons Ltd.)

Hemarthroses and muscle bleeds are well-known and well-documented complications in pediatric and young adult hemophilia patients. In contrast, deep bleeds in atypical locations can be a diagnostic challenge, since clinicians and radiologists are often unfamiliar with their clinical and radiological features. Some atypical bleeds, however, can be life-threatening or severely disabling, highlighting the need for prompt, accurate diagnosis. Rare bleeds include central nervous system bleeds (including intracranial and spinal hematomas), urogenital bleeds, intra-abdominal bleeds (mesenteric and gastrointestinal wall hematomas) and pseudo tumors in unusual locations like the sinonasal cavities. Because clinical assessment can be difficult, clinicians and radiologists should be aware of the possibility of these rare complications in their hemophilia patients, so that they can avoid unnecessary invasive diagnostic and surgical procedures and institute prompt, appropriate treatment. The purpose of this review is to illustrate the imaging features of bleeds that occur in rare locations in young (i.e., children and young adults) patients with hemophilia to make the reader more familiar with these conditions., (Copyright © 2018 Société française de radiologie. Published by Elsevier Masson SAS. All rights reserved.)

To investigate the incidence, risk factors, clinical manifestations and prognosis of intracranial hemorrhage (ICH) in children with hemophilia A in a center of China, we conducted a retrospective analysis of 126 children with hemophilia A at our hospital in recent 4 years. Thirty-six children with hemophilia A (including 19 severe cases, and 17 moderate cases complicated with joint diseases) received low dose factor VIII (FVIII) prophylaxis, and none of them had ICH. However, 13 cases of hemophilia A not given prophylaxis were complicated with ICH (12 severe cases, and 1 moderate case) and demonstrated an incidence of 10.3% (13/126) in all patients, and 28.6% (12/42) in severe cases. Of the 13 cases, 9 severe ICH cases had a definite history of head injury, accounting for 69.2%. Headache was common in children >3 years, but somnolence, irritability, gaze or convulsions in children <3 years. The most common findings of cranial CT scan included intracranial hematoma (9/13), and less commonly observed were subependymal hemorrhage and intraventricular hemorrhage. After administration of FVIII, all patients survived. Hematoma of 6 cases was observed during CT reexamination after 1-3 months. During the follow-up period, only one case had slight activity limitation on one side of the limb, but steadily recovered. Besides the decreased concentration of FVIII, trauma is the most common risk factor of ICH in children with hemophilia A. The active treatment can improve the prognosis of ICH in children with hemophilia A.

Background: Outcomes of total knee replacement in cases of hemophilic patients are worse than in patients who undergo operations due to osteoarthritis. Previous publications have reported varying rates of complications in hemophilic patients, such as infection and an unsatisfactory range of motion, which have influenced the survival of prostheses. Our retrospective study evaluated the data of hemophilic patients regarding changes in the development of the range of motion., Methods: The data and clinical outcomes of 72 total knee replacements in 45 patients with hemophilia types A and B were reviewed retrospectively. Patients were operated between 1998 and 2013. All of the patients were systematically followed up to record the range of motion and other parameters before and after surgery., Results: The mean preoperative flexion contracture was 17° ± 11° (range, 0°-40°), and it was 7° ± 12° (range, 0°-60°) postoperatively. The mean flexion of the knee was 73° ± 30° (range, 5°-135°) before the operation and 80° ± 19° (range, 30°-110°) at the last follow-up. The mean range of motion was 56° ± 34° (range, 0°-130°) before the operation and 73° ± 24° (range, 10°-110°) at the last follow-up., Conclusions: Statistical analysis suggested that the range of motion could be improved until the 9th postoperative week. The patient should be operated on until the flexion contracture reaches 22° to obtain a contracture < 15° postoperatively or until the contracture reaches 12° to obtain less than 5°. The operation generally does not change the flexion of the knee in cases of hemophilic patients, but it reduces the flexion contracture and therefore improves the range.

Objective: The purpose of this study was to assess the feasibility of 3-T susceptibility-weighted imaging (SWI) for detecting intraarticular hemosiderin accumulation in patients with hemophilia., Subjects and Methods: Forty-one joints in 24 patients with hemophilia were imaged with conventional MRI and SWI sequences. Two experienced musculoskeletal radiologists and one general radiologist (reader 3) interpreted the images for hemosiderin accumulation. The final decision was determined in consensus by readers 1 and 2 using both conventional MRI and SWI sequences. The diagnostic consistencies of each MRI sequence with the reference and pairwise agreements between interpreters were assessed., Results: For conventional MRI sequences, the diagnostic consistencies of the two experienced musculoskeletal radiologists with the reference were substantial (κ = 0.63 and 0.62), whereas the consistency of the general radiologist with the reference was moderate (κ = 0.47). The SWI interpretations of all readers had almost perfect agreement with the reference (κ = 1, κ = 1, κ = 0.97). Interobserver agreement also improved at SWI interpretations., Conclusion: SWI contributes to more accurate grading of intraarticular hemosiderin accumulation than is achieved with conventional MRI sequences.

Essentials The best imaging modality for joint blood detection in hemophilia is unknown. Blood appearance and detection thresholds were studied with ultrasound and conventional MRI. Ultrasound is sensitive to low volume and concentration of blood, whereas conventional MRI is not. The findings establish the validity of ultrasound for rapid bleed detection in hemophilia care., Summary: Background There is increasing demand for musculoskeletal ultrasound (MSKUS) to detect hemophilic joint bleeding, but there is uncertainty regarding blood detection concentration thresholds or if magnetic resonance imaging (MRI) is more accurate. Aims Compare the sensitivity of blood detection by MSKUS and MRI. Methods Increasing blood concentrations in plasma were imaged with MSKUS and MRI 1-2 h, 3-4 days and 7 days after blood withdrawal in vitro, and after injection into cadaveric pig joints. Additionally, effusions in the joints of two patients with hemophilia joints were imaged, followed by aspiration. MSKUS was performed using an 8-18-MHz linear transducer; MRI was performed at 3T using T1-weighted and T2-weighted fat-suppressed sequences. Images were reviewed by a hematologist certified in MSKUS and a musculoskeletal radiologist. Results MSKUS permitted the detection of blood in vitro and in pig joint spaces at concentrations as low as 5%, demonstrated by the presence of echogenic signals that were absent with plasma alone. In contrast, no differences between fluids were discernible on the T1-weighted or T2-weighted MRI images. Results were confirmed in the two patients with hemophilia. Blood clots demonstrated varying and dynamic echogenicity patterns over time and, using MRI, were visualized best with T2 sequences. Conclusion MSKUS is extremely sensitive in detecting low concentrations of intra-articular blood and in discriminating between bloody and non-bloody fluid, whereas conventional MRI is not. These observations demonstrate the advantages of MSKUS over MRI in detecting intra-articular blood, and show that MSKUS is ideal for rapid bleed detection in the clinic., (© 2017 International Society on Thrombosis and Haemostasis.)

Background: Prevention of hemarthrosis is the key factor in the adequate management of people with hemophilia (PWH). If hemarthrosis occurs, early diagnosis of joint damage is essential to make personalized treatments. This study is aimed at gaining an understanding of the ability of point-of-care ultrasound (US) using the `Hemophilia Early Arthropathy Detection with Ultrasound´ (HEAD-US) protocol to detect abnormalities in joints without history of hemarthrosis and clinically asymptomatic joints of PWH., Methods: The sample included 976 joints from 167 PWH (mean age 24.86 years). Data were collected from routine practice over a 3-year period and analyzed based on history of hemarthrosis and results of clinical (HJHS 2.1) and HEAD-US examinations., Results: In our series, 14% of patients exhibited HEAD-US signs of incipient arthropathy in joints with no history of bleeding and with a HJHS 2.1 score of 0. The most severely involved joint was the right ankle. Synovitis, articular cartilage and subchondral bone damage scores in joints with subclinical findings were slower than in joints with previous hemarthroses or HJHS 2.1 > 1 Conclusions: Our study demonstrates that HEAD-US is better than hemarthrosis records and the HJHS 2.1 scale in detecting the early signs of joint damage in PWH.

Clotting factor replacement therapy alone is often inadequate for acute bleeding in hemophilia patients, and surgery for such patients poses significant clinical challenges. Arterial angiographic intervention is used to control bleeding in local blood vessels. In the present study, we examined the clinical course and prognosis of hemophilia patients with bleeding who had undergone angiography, and evaluated the validity of diagnostic angiography and therapeutic embolization in these patients. Angiography was performed in five hemophilia patients, who experienced bleeding that was difficult to control even after treatment with clotting factor replacement or bypassing agent therapy. Of these patients, four were confirmed to have continued bleeding, and angiographic embolization was performed using clotting factor concentrates or bypassing agents. However, one patient developed uncontrollable bleeding at the puncture site, which eventually led to the patient's death. Thus, angiography and therapeutic embolization may be the preferred procedures for the treatment of hemorrhagic complications, refractory to treatment with clotting factor concentrates or bypassing agents. Further comprehensive, multidisciplinary team studies are needed to develop effective strategies to reduce hemorrhagic complications.

Many risk factors may contribute to renal disease in patients with hemophilia A., Aim: We aimed to evaluate functional and structural renal abnormalities among a group of Egyptian children with severe and moderate hemophilia A using technetium-99m diethylene triamine pentaacetic acid ( 99m Tc-DTPA) and technetium-99 m dimercaptusuccinic acid ( 99m Tc-DMSA) scan. We also aimed to determine the relation between these abnormalities and different risk factors and disease severity., Patients and Methods: Forty male patients, 16 with severe and 24 with moderate hemophilia A, were enrolled in this study. Their mean age was 10.2 ± 4.3 years (range, 5-17 years). Full history taking, clinical examination, laboratory, and radionuclide investigations including serum creatinine, blood urea nitrogen (BUN), urine analysis, creatinine clearance, 24-hour urinary protein, 99m Tc-DTPA scan, and 99m Tc-DMSA scan were performed to all enrolled patients., Results: Serum creatinine and BUN were normal in all patients, and corrected creatinine clearance was diminished in 2 patients. However, 99m Tc-DTPA results yielded 19 (47.5%) patients with diminished glomerular filtration rate (GFR). Moreover, it showed that 14 (35%) had obstructive uropathy, 15 (37.5%) had obstructive nephropathy, while 11 (27.5%) patients showed normal scan. One patient had atrophy of 1 kidney on 99m Tc-DMSA scan. Among our cohort, 5 (12.5%) patients were hypertensive. Microscopic hematuria was detected in 14 (35%) patients while 72.5% had proteinuria. We found an association between hematuria and hypertension with diminished GFR., Conclusion: Despite normal kidney functions (serum creatinine and BUN), we found a high rate of diminished GFR and obstructive uropathy and nephropathy as detected by 99m Tc-DTPA scan among children with hemophilia A.

Purpose: Increased articular 99m Tc MDP uptake on blood pool imaging (BPI) of patients with rheumatologic conditions is indicative of active inflammatory changes, and has been suggested as a strong predictor of response to radiosynoviorthesis (RSO). In this study, we aimed to assess the value of pretreatment BPI positivity (i.e. scintigraphic-apparent hyperemia) for successful RSO in hemophilic arthropathy., Methods: Thirty-four male patients with painful hemophilic arthropathy underwent RSO after failure of conservative treatment. Treated joints comprised the knee in eight, elbow in five, and ankle in 21 patients. Pretreatment triple-phase bone scintigraphy showed hyperemic joints (pathologic BPI) in 17 patients, whereas 17 patients had no increased tracer uptake on BPI. Response to RSO was evaluated 6 months post-treatment by measuring changes in intensity of arthralgia according to the visual analog scale (VAS), bleeding frequency, and range of motion. The association between hyperemia (pathologic BPI) and treatment outcome was examined using nonparametric tests for independent samples., Results: Clinically evident pain relief occurred in 26 patients (76.5 %), and the mean VAS decreased from 7.7 ± 1.1 to 4.6 ± 2.7 (p < 0.001). Joint bleeding frequency (hemarthrosis) decreased from 4.5 ± 0.6 to 2.1 ± 0.4 during the first 6 months after RSO (p < 0.001). For both parameters (pain relief and bleeding frequency), patients experienced a similar benefit from RSO regardless of pretreatment BPI: arthralgia (p = 0.312) and frequency of hemarthrosis (p = 0.396). No significant improvement was observed for range of motion, but it was significantly more restricted in hyperemic joints both before (p = 0.036) and after treatment (p = 0.022)., Conclusions: Hemophilic arthropathy can be effectively treated with RSO regardless of pre-therapeutic BPI. Patients in whom articular hyperemia is not detectable by scintigraphy may have similar (outstanding) outcomes, and thus should not be excluded from treatment.

Aim: Using diffusional kurtosis imaging (DKI) to assess the impact of emotional disorders on microstructural changes of the brain in children with haemophilia A., Materials and Methods: Diffusional kurtosis imaging was acquired from haemophilia A (n = 22) and controls (n = 22) using a 3T scanner. A regression analysis of frontal, cingulate, hippocampus, insula and amygdala regions of interest (ROIs) was conducted. Clinical data and results of psychological tests were collected. A paired t-test was used to analyse the differences between the two groups' ROIs, and the Spearman test was used to analyse the correlation between ROIs and psychological tests or clinical data., Results: Fractional anisotropy (FA) in the left middle cingulate and right hippocampus; mean diffusion (MD) in the frontal lobe, right anterior cingulate and right middle cingulate showed varying degrees of increase in the ROI compared to controls (P < 0.003). MD in the frontal lobe and the course of disease (P < 0.05), FA in the right hippocampus and the social score of the self-consciousness scale (P < 0.01) had a positive correlation., Conclusion: Our study is the first to evaluate the relationship between emotion disorders and cognitive changes in the microstructure of the brain in children with haemophilia A, suggesting that DKI provides more information about tissue microstructural changes than do the conventional image method and traditional psychological tests., (© 2017 John Wiley & Sons Ltd.)

Introduction: A major complication of haemophilia is haemophilic arthropathy (HA), a debilitating disorder with an incompletely defined pathobiology. High-resolution imaging may provide new knowledge about onset and progression of HA, and thereby support identification of new treatment opportunities. Recently, a F8 -/- rat model of HA was developed. The size of the rat allows for convenient and high resolution imaging of the joints, which could enable in vivo studies of HA development., Aim: To determine whether HA in the F8 -/- rat can be visualized using ultrasonography (US) and micro-computed tomography (μCT)., Methods: Sixty F8 -/- and 20 wild-type rats were subjected to a single or two induced knee bleeds. F8 -/- rats were treated with either recombinant human FVIII (rhFVIII) or vehicle before the induction of knee bleeds. Haemophilic arthropathy was visualized using in vivo US and ex vivo μCT, and the observations correlated with histological evaluation., Results: US and μCT detected pathologies in the knee related to HA. There was a strong correlation between disease severity determined by μCT and histopathology. rhFVIII treatment reduced the pathology identified with both imaging techniques., Conclusion: US and μCT are suitable imaging techniques for detection of blood-induced joint disease in F8 -/- rats and may be used for longitudinal studies of disease progression., (© 2016 John Wiley & Sons Ltd.)

Introduction and Objectives: Intra-articular corticosteroid injections are standard of care for managing joint pain secondary to osteoarthritis or rheumatoid arthritis but are rarely used in haemophilic arthropathy. We have introduced and evaluated the efficacy and safety of ultrasound-guided corticosteroid injections for pain relief in patients with haemophilic arthropathy., Patients and Methods: Ultrasound-guided intra-articular injections performed on haemophilia patients at UCSD between March 2012 and January 2016 were analysed. Needle placement and injection (40 mg triamcinolone; 3-5 mL lidocaine) were performed with musculoskeletal ultrasound and Power Doppler. Analysis included patient demographics, joint-specific parameters such as tissue hypervascularity and effusions, pain relief, and procedure-associated complications., Results: Forty-five injections (14 ankles, 13 elbows, 18 knees) were administered in 25 patients. Advanced arthropathy with hypervascularity and/or effusions was present in 91% and 61% of joints, respectively. Ninety-one per cent of injections resulted in pain relief which was significant in 84% (>30% reduction). Median pain score was reduced from 7 of 10 to 1 of 10 (P < 0.001), usually within 24 h. Median duration of pain relief was 8 weeks (range 1-16 weeks). Haemophilia B patients experienced longer periods of relief, and high Pettersson scores were associated with shorter duration of relief. There were no procedure-associated complications. Repeat ultrasound of eight joints within 4 weeks of injection demonstrated nearly complete resolution of hypervascularity., Conclusions: Point-of-care ultrasound enabled intra-articular corticosteroid injections that provided highly effective, safe, and relatively long-lasting pain relief in haemophilic arthropathy. This approach should be used to improve pain management in haemophilic arthropathy., (© 2016 John Wiley & Sons Ltd.)

The role of arthroscopic debridement of the knee in haemophilia is controversial in the literature. The purpose of this study is to describe the results of arthroscopic knee debridement (AKD), with the aim of determining whether it is possible to delay total knee replacement (TKR) for painful moderate haemophilic arthropathy of the knee in adult patients. In a 14-year period (1998-2011), AKD was performed for moderate haemophilic arthropathy of the knee in 27 patients with haemophilia A. Their average age at operation was 28.6 years (range 26-39 years). Indications for surgery were as follows: more than 90° of knee flexion, flexion deformity less than 30°, good axial alignment of the knee, good patellar alignment, and pain above >60 points in a visual analogue scale [0 (no pain) to 100 points]. Secondary haematological prophylaxis and rehabilitation (physiotherapy) was given for at least 3 months after surgery. Follow-up was for an average of 7.5 years (range 2-14 years). We assessed the clinical outcome before surgery and at the time of latest follow-up using the Knee Society pain and function scores, the range of motion, and the radiological score of the World Federation of Haemophilia. Knee Society pain scores improved from 39 preoperatively to 66 postoperatively, and function scores improved from 36 to 52. Range of motion improved on an average from -15° of extension and 90° of flexion before surgery, to -5° of extension and 110° of flexion at the last follow-up. A radiological deterioration of 2.8 points on average was found. There were two (7.4%) postoperative complications (haemarthroses resolved by joint aspiration). One patient (3.7%) required a TKR 12.5 years later. AKD should be considered in painful moderate haemophilic arthropathy of the knee in adult patients to delay TKR.

Joint hemorrhages represent the most common type of bleeding episode in persons with hemophilia, and recurrent hemarthrosis triggers chronic arthropathy, which is the most frequent chronic complication in these patients. In recent years, in the frame of a comprehensive care approach, a growing attention has been given to the periodic assessment of the joint status in hemophilia patients with the aim to identify early arthropathic changes and to prevent the development of a clinically overt arthropathy. Besides clinical examination, X-ray and magnetic resonance imaging (MRI) are currently used to evaluate joint status and to monitor the disease progression in hemophilia. Considering the limitations of X-ray and MRI, growing interest has been given to ultrasound (US) as a possible tool to assess joint status and identify early arthropathic changes in hemophilia patients. In the present review, we summarize major literature evidence on the use of joint US for the evaluation of markers of disease activity (joint effusion and synovial hypertrophy) and of degenerative damages (osteochondral changes) in patients with hemophilia. On the whole, being able to identify the presence of intra- or extra-articular fluid, US examination is the fastest and most reliable technique to identify acute conditions, such as hemarthrosis. In addition, the information on joint involvement provided by US in the patient follow-up may influence treatment decisions on a personalized basis. The use of US as part of a routine clinical examination by hemophilia experts may optimize the diagnostic workflow, avoiding additional costs and long waiting lists for patients referred to imaging departments. In the frame of a comprehensive care approach, US might represent a strategy to early detect and monitor synovial hypertrophy and osteochondral changes in hemophilia, thus extending the clinical examination and helping identify joints to be studied with a second-level examination such as MRI., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Evaluation of joints in children with haemophilia is important in detecting abnormalities, staging their severity and following the effects of treatment. The aim of this study is to evaluate the correlation of FISH score (Functional Independence Score in Haemophilia) with the scores obtained by MRI and sonography for the diagnosis, evaluation and classification of arthropathy in severe haemophilia. In this cross-sectional study on 25 severe haemophilia patients, FISH, MRI and sonography procedures were performed in the elbow or knee joint. All patients' information, including age, type of haemophilia, affected joint, scores of MRI, sonography and FISH, dose of factor consumed, weight and prophylaxis protocol were collected and analysed. Among the 25 patients (age range of 11-70 years), 22 patients were haemophilia A and three patients were haemophilia B. Affected joints were right knee in 12 patients, left knee in nine and right elbow in four. There was only a statistically significant negative correlation between FISH and MRI Additive (A) scale (rs = -0.537, P = 0.006). Considering cartilage loss domain (related MRI A scale: 13-20), 20 patients (80%) were classified in this group with FISH scores ranged from 17 to 22. On the basis of our results, FISH scores in severe haemophilia patients were negatively correlated with MRI A scale. Also, it seems that a FISH score less than 22 could be considered as loss of cartilage; however, due to the small number of our patients, it needs further assessment in different populations.

Recent evidence suggests that patients with severe hemophilia B may have a less severe disease compared to severe hemophilia A. To investigate clinical, radiological, laboratory and histological differences in the arthropathy of severe hemophilia A and hemophilia B, 70 patients with hemophilia A and 35 with hemophilia B with at least one joint bleeding were consecutively enrolled. Joint bleedings (<10, 10-50, >50), regimen of treatment (prophylaxis/on demand), World Federation of Hemophilia, Pettersson and ultrasound scores, serum soluble RANK ligand and osteoprotegerin were assessed in all patients. RANK, RANK ligand and osteoprotegerin expression was evaluated in synovial tissue from 18 hemophilia A and 4 hemophilia B patients. The percentage of patients with either 10-50 or more than 50 hemarthrosis was greater in hemophilia A than in hemophilia B (P<0.001 and P=0.03, respectively), while that with less than 10 hemarthrosis was higher in hemophilia B (P<0.0001). World Federation of Hemophilia (36.6 vs. 20.2; P<0.0001) and ultrasound (10.9 vs. 4.3; P<0.0001) score mean values were significantly higher in hemophilia A patients. Serum osteoprotegerin and soluble RANK ligand were decreased in hemophilia A versus hemophilia B (P<0.0001 and P=0.006, respectively). Osteoprotegerin expression was markedly reduced in synovial tissue from hemophilia A patients. In conclusion, the reduced number of hemarthrosis, the lower World Federation of Hemophilia and ultrasound scores, and higher osteoprotegerin expression in serum and synovial tissue in hemophilia B suggest that hemophilia B is a less severe disease than hemophilia A. Osteoprotegerin reduction seems to play a pivotal role in the progression of arthropathy in hemophilia A., (Copyright© Ferrata Storti Foundation.)

Imaging assessment is an important tool to evaluate clinical joint outcomes of hemophilia. Arthropathic changes have traditionally been evaluated by plain radiography and more recently by ultrasound and magnetic resonance imaging (MRI). Early arthropathic changes can be identified by modern imaging techniques such as T2 mapping MRI of cartilage even before clinical symptoms become apparent. Cross-sectional imaging modalities such as CT, ultrasonography, and MRI are useful in assessing bleeding-related musculoskeletal complications such as pseudotumors that still exist in some parts of the world. This article provides an overview of imaging of hemophilic arthropathy, and discusses the role and scope of individual imaging modalities currently in use in clinical practice, as well as of promising techniques that require further investigation in the immediate future., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)