Incidence of Ultrasonographically Detected Articular Damage in Initially Healthy Joints of Patients With Hemophilia A Receiving Prophylactic Treatment With Emicizumab

Ultrasonographically detected articular damage will be assessed using the Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) protocol through standardized musculoskeletal ultrasound examination. This scoring system evaluates three structural domains per joint: synovial (hypertrophy and effusion), cartilage, and bone. Each joint is assigned an ordinal score ranging from 0 (no abnormalities) to a maximum of 8 points, derived from the combined assessment of the synovial, cartilaginous, and osseous domains. The HEAD-US protocol enables detection of subclinical joint damage and early structural changes, even in the absence of clinically evident hemarthrosis.Scree

Clinical joint health will be assessed using the Hemophilia Joint Health Score, version 2.1 (HJHS 2.1). This instrument evaluates eight items per joint: swelling (edema), duration of swelling, pain, muscle atrophy, crepitus, strength deficit, loss of range of motion, and joint deformity. Additionally, it includes a global gait assessment scored from 0 to 4. Each item is rated on an ordinal scale according to the instrument's predefined criteria, yielding a per-joint score ranging from 0 to 20 and a total score ranging from 0 to 124. Higher scores indicate worse clinical joint health.

This variable will be assessed using the Annualized Joint Bleeding Rate (AJBR), calculated as the number of hemarthroses occurring during the observation period divided by the total days of follow-up and multiplied by 365.25. The AJBR will be calculated both globally and on a per-joint basis, based on systematically recorded bleeding events obtained through structured clinical interviews.

This variable will be assessed using the Physical Activity Questionnaire for Adolescents (PAQ-A). The PAQ-A consists of nine items evaluating participation in various types of physical and sports activities; frequency of activity during physical education classes; activity during recess and leisure time; after-school activity; weekend activity; and overall level of habitual physical activity. Each item is scored on a 5-point Likert scale (1 to 5), and the final score corresponds to the mean of all items. Higher scores indicate a greater level of habitual physical activity.

This variable will be assessed using the International Physical Activity Questionnaire - Long Form (IPAQ-LF). The IPAQ-LF captures physical activity across four domains: work-related physical activity, active transportation, domestic and household activities, and leisure-time physical activity. Within each domain, the time spent in vigorous-intensity activity, moderate-intensity activity, and walking is recorded, allowing for the calculation of total energy expenditure expressed in MET-minutes per week (MET-min/week).

This variable will be assessed using the Torres questionnaire for treatment adherence in hemophilia. This hemophilia-specific instrument evaluates five dimensions: disease awareness, perceived sequelae, treatment-related difficulties, physician-patient relationship, and hemorrhagic processes. Higher scores indicate greater adherence within the corresponding domain.

This variable, used to describe the sample and control for potential confounding factors, will be measured as a quantitative variable (in years)

This variable, used to describe the sample and control for potential confounding factors, will be measured as an ordinal variable (severe / moderate / mild).

This variable, used to describe the sample and control for potential confounding factors, will be measured as a dichotomous variable (yes / no)

This variable, used to describe the sample and control for potential confounding factors, will be measured as a quantitative variable (in years).