Hemophilia is a genetic condition characterized by marked phenotypic heterogeneity. Bleeding into a joint is the single most important risk factor for the development of hemophilic arthropathy (HA). It is thought that clinical and imaging manifestations of HA are at least partially attributable to genetic polymorphisms unrelated to the hemophilia genotype. Identifying and characterizing biologic factors that could explain differences in susceptibility to joint degeneration of patients with hemophilia would help stratify patients according to the risk of degeneration of their joints and develop personalized therapeutic and prophylactic strategies. This study is conducted in China.

This will be a 3-year prospective cohort study conducted in a single centre (Beijing Children's Hospital, BCH, China) with a 2-year follow-up of patients Index joints (ankles, elbows and knees) of young Chinese boys with hemophilia A will be evaluated as follows: physical examination every 6 months using the Hemophilia Joint Health Score [HJHS], ultrasound imaging (gray-scale and color Doppler ultrasound [US]), and by laboratory (serum) at baseline, at 6, and 24 months. Magnetic resonance imaging (MRI) scans of index joints will be obtained at baseline, and 24 months. Features that will be captured either quantitatively or semantically in the imaging scans will be aggregated to generate "imaging phenotypes" which will be associated with clusters of co-expressed genes (metagenes) and clinical data.

Inclusion Criteria:

• Hemophilia A with baseline FVIII levels of <2%
• Clinical history of ≥ 50 exposure days to FVIII prior to the study start.
• On-demand treatment, prophylaxis FVIII infusions or treatment with plasma-derived products for >3 months prior to enrollment into the study.

Exclusion Criteria:

• History of FVIII inhibitor (titer >0.6 Bethesda Units [BU])
• Chronic renal failure (serum creatinine >2.0 mg /dL).
• Chronic liver disease (alanine aminotransferase [ALT] >200 U/L).
• Clinically documented immunodeficiency.
• Anticipation of need for major surgery during the study period.
• Association of diseases known to mimic or cause joint diseases such as symptomatic human immunodeficiency virus (HIV) infection, juvenile idiopathic arthritis, and metabolic bone diseases.
• Social barriers for participation in the study such as long distance between home and the comprehensive care centre, and documented track record of non-compliance to therapies or participation in clinical studies.
• Neuro-developmental/behavioral problems.
• Contraindications to MR imaging (presence of heart pacemakers, metallic foreign bodies in the eye, aneurysm clips, severe claustrophobia).