This is an observational research study to find out if there is a difference in the way children with moderate or severe hemophilia A, treated on two different types of factor replacement, form a clot and also evaluate if they develop tiny bleeds within the joint and subsequently early joint changes when receiving extended half-life factor VIII.

This research study aims to compare the differences in the way children with moderate or severe hemophilia A respond when being treated with prophylactic extended half-life factor VIII based replacement therapy (such as Altuviiio) vs non-FVIII based replacement therapy (such as Hemlibra) as part of their hemophilia treatment to prevent spontaneous joint bleeds. This study will collect information about the patient's joint health, patient outcomes (using questionnaires), and laboratory testing at specific time points over 3 years.

The study will use an overall approach of comparative effectiveness research (CER) methodology. We plan to recruit participants with severe (FVIII <1%) and moderate (FVIII 1-4%) HA who take extended half-life factor VIII based replacement therapy or non-FVIII based replacement therapy as their clinically prescribed treatment. Both are standard of care treatment for persons with Hemophilia A (PwHA). Using CER principals, this study will analyze differences in 1) hemostatic potential and annualized bleeding rates (Aim 1-3) and 4) joint health (structural and functional) using the Hemophilia Joint Health Score (HJHS) and imaging markers to identify subclinical bleeding and early joint tissue changes in PwHA on novel FVIII and non-FVIII therapies already in use in practice (Aim 4). The proposed study will be the first systematic observational comparative effectiveness study in PwHA on two conventional, standard-of-care novel therapies with differing mechanisms of action to evaluate the overall effectiveness of treatment.

Inclusion Criteria:

• Participants with moderate or severe HA who are on prophylaxis with either weekly, biweekly, or every 4-weeks emicizumab or weekly efanesoctocog alfa for at least 2 months.
• >6 months of age

Exclusion Criteria:

• Participants with active FVIII inhibitor (>0.5 BU/mL)
• Presence of an additional bleeding disorder other than hemophilia A

• Children (defined as persons who have not attained the legal age for consent to treatments or procedures involved in the research, under the applicable law of the jurisdiction in which the research will be conducted. In Texas the legal age is 18.)
• Non-English Speakers
• Patients (defined as individuals in a clinical setting with whom there is a treatment relationship)