Diagnostic Value of the HEAD-US-C Scale for the Knees of Severe Hemophilia A Patients.

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.

Teleguidance for Patient Self-Imaging of Hemophilic Joints Using Mobile Ultrasound Devices: A Pilot Study.

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.

Consistency of serial ultrasonographic joint tissue measurements by the Joint tissueActivity and Damage Exam (JADE) protocol in relation to hemophilic joint health parameters.

OBJECTIVES: The Joint tissueActivity 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.

Treatment Individualization Using Pharmacokinetic Studies and Joint Ultrasound Imaging in Pediatric Patients With Hemophilia.

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.

The musculoskeletal manifestations of haemophilia: a review of the imaging findings.

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.

The role of point-of-Care Musculoskeletal Ultrasound for Routine Joint evaluation and management in the Hemophilia Clinic - A Real World Experience.

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 TissueActivity 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.

Computed Tomography Scans in Children With Hemophilia After Minor Head Trauma.

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.

Comparison of the clinical and ultrasound evaluation of haemophilic arthropathy in children.

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 50th 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.

ANTECEDENTES: La exploración articular por ultrasonido mediante el método HEAD-US en la detección de la artropatía temprana ha sido poco estudiada en nuestro país. OBJETIVO: Comparar la evaluación clínica y por ultrasonido de las articulaciones en niños con hemofilia. MÉTODOS: Estudio longitudinal, prospectivo y descriptivo con pacientes pediátricos con hemofilia A y B valorados con la escala HJHS 2.1 y ultrasonido con transductor lineal de 8 a 12 MHz. Se evaluaron las articulaciones de codos, rodillas y tobillos de forma bilateral, con el método HEAD-US. RESULTADOS: Se incluyeron 69 pacientes; de ellos, 48 con hemofilia A grave (peso: 40.1 kg). En la escala HJHS se observó mayor afectación en la rodilla izquierda (0.49) y menor en el tobillo derecho (0.05). Con la escala HEAD-US, la más afectada fue la rodilla derecha (0.78). Existe una relación significativa en la afectación de la rodilla derecha evaluada con la escala HEAD-US en presencia de inhibidor. CONCLUSIONES: El peso superior al percentil 50 es un factor de riesgo independiente de complicaciones por sangrado articular, mientras que la edad y el tipo de hemofilia no parecen relacionados. El método HEAD-US es una herramienta útil y accesible para la detección temprana de artropatía y hemartrosis.

Ultrasound and magnetic resonance imaging for the detection of blood: An ex-vivo study.

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.

Chromic phosphate-32 colloid radiosynovectomy for the treatment of haemophilic synovitis: A long-term follow-up study.

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.

Contribution of 3-T Susceptibility-Weighted MRI to Detection of Intraarticular Hemosiderin Accumulation in Patients With Hemophilia.

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.

Range of motion after total knee arthroplasty in hemophilic arthropathy.

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.

Premature changes in trabecular and cortical microarchitecture result in decreased bone strength in hemophilia.

Low bone density is a growing concern in aging men with hemophilia and may result in high-morbidity fragility fractures. Using high-resolution peripheral quantitative computed tomography (HR-pQCT), we demonstrate low trabecular and cortical bone density contributing to lower volumetric bone mineral density (BMD) at both distal radius and tibia in patients with hemophilia compared with age- and sex-matched controls. The low trabecular bone density found in hemophilia is attributed to significantly decreased trabecular number and increased separation; the lower cortical bone density results from thinner cortices, whereas cortical porosity is maintained. Microfinite element analysis from three-dimensional HR-pQCT images demonstrates that these microarchitectural deficits seen in patients with hemophilia translate into significantly lower estimated failure load (biomechanical bone strength) at the distal tibia and radius when compared with controls. In addition, an inverse association of joint score with BMD and failure load suggests the negative role of hemophilic arthropathy in bone density loss.

Radiosynoviorthesis in hemophilic arthropathy: pathologic blood pool imaging on pre-therapeutic bone scintigraphy is not a predictor of treatment success.

PURPOSE: Increased articular 99mTc 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.

Visualization of haemophilic arthropathy in F8-/- rats by ultrasonography and micro-computed tomography.

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.

Preliminary evaluation of altered brain microstructure in the emotion-cognition region in children with haemophilia A: a diffusional kurtosis imaging study.

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.

Efficacy and safety of point-of-care ultrasound-guided intra-articular corticosteroid joint injections in patients with haemophilic arthropathy.

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.

Assessment of Hemophilic Arthropathy by Ultrasound: Where Do We Stand?

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.

Clinical, instrumental, serological and histological findings suggest that hemophilia B may be less severe than hemophilia A.

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.