The investigators propose to study longitudinal joint and bone density changes in patients with severe Hemophilia A. Per current standard of care, most patients are on prophylactic FVIII replacement therapy intravenously several times weekly with a goal of keeping the trough >1% FVIII. Recent phase 3 data suggest superior bleed protection with emicizumab prophylaxis every 1-2 weeks. It is the purpose of this study to longitudinally assess joint health and bone density over 3 years and to compare the effect of routine factor VIII prophylaxis with emicizumab prophylaxis.

Summary: This retrospective/prospective, non-randomized controlled study, whereby patients will be included in 1 of 2 groups depending on their current treatments as outlined below. Patients will be assigned to a specific group by the clinician/PI based on their current regimen with the intent to stay on this regimen for the next 3 years.

Duration of Study and Subject Participation: Study subject enrollment is anticipated to occur over about 12 months and study duration per subject will be 3 years. Thus a total study duration of 4 years is anticipated.

Intervention: By using musculoskeletal ultrasound, the investigators will measure joint health among participants and assess joint health changes over 3 years compared between group A (factor prophylaxis) vs. group B (emicizumab prophylaxis) as assessed by MSKUS at baseline and after 3 years. Other outcomes such as bone density, comparative assessment of joint and overall health status, and exploration of potential biomarkers for joint and bone health will also be assessed.

Inclusion Criteria:

• Male gender
• Severe hemophilia A (factor VIII < 1%)
• Age ≥ 16 year
• Either on prophylaxis with factor VIII or emicizumab with the intention to stay on the current regimen for the next 3 years
• Willing and able to give written informed consent/assent
• Willing to undergo MSKUS, DEXA scan +/- collection of blood sampling for repository biomarkers
• Willing to come in for baseline and 3 yearly visits
• Willing to answer phone survey for bleeding and safety every 3 months

Exclusion Criteria:

• Current FVIII inhibitor of > 0.6 BU
• Unable to take FVIII replacement
• Other known bleeding disorder
• Other rheumatologic disorder affecting joints
• Other known neuromotor defect (making physical exam difficult)

Male severe Hemophilia A patients at one of the several Hemophilia Treatment Center sites participating in this study and who meet the eligibility criteria and are interested in participating in the study.