Hemophilia is an inherited disease caused by deficiency in varying degrees of clotting factors VIII and IX. Depending on the percentage of clotting factor in the blood the disease is categorized as "severe" (<1%, characterized by spontaneous bleedings), "moderate" (1-5%) and "mild" (>5%). If untreated, recurrent bleeding into the synovial joints often results in irreversible damage due to destruction of the cartilages and progressive joint impairment.

3d-gait analysis has been demonstrated as valid method to assess abnormal gait patterns and to monitor disease progression in patients with hemophilia (PWH). Furthermore, its outcomes facilitate the design of individually tailored therapeutic programs. In contrast to radiological examinations, 3d-gait analyses take place under weight-bearing conditions, which is a relevant issue in terms of weight-induced pain.

This study aims to explore the applicability of 3-d gait analysis as biomarker (gait deviation index) for functional impairments in PWH. Besides 3-d gait scores, secondary endpoints such as biomarkers reflecting cartilage damage and a laterality-ratio of leg muscle mass (in the case of one-sided target joints) will be tested for their ability to detect functional impairments in young adults with hemophilia.

Based on sample size calculation, 24 subjects aged 16-49 years, able to walk without aids or assistance will be included in each of the two groups: control (healthy, male), PWH (severe or moderate, treated prophylactically). Subjects suffering from functional impairments caused by other conditions than hemophilia, patients with bleedings within 30 days prior to the examination, PWH treated with immune-tolerance therapy and/or not successfully treated present or past high-titer factor VIII or FIX inhibitor will be excluded.

Subjects will pass through a set of examinations (medical history, clinical examination, 3d-gait analysis, anthropometrics, body composition analysis, venipuncture, and urine sampling) and carry an accelerometer device for seven consecutive days.

Confounder adjusted group differences will be assessed by ANCOVA with contrasts and Bonferroni correction. Correlations between the applied examination approaches will be assessed.

An evidence based health promotion program including follow-up examinations, physical activity promotion, and tailored physiotherapy are being envisaged as a follow-up project (JOSEPHA phase 2).

Inclusion Criteria (test group):

• Provide signed and dated informed consent form (additionally from guardian for participants aged under 18 years)
• Willing to comply with all study procedures and be available for the duration of the study
• Diagnosed severe or moderate hemophilia A or B
• Age between 16 and 49 years
• Able to walk without aids or assistance
• Treated with prophylactic substitution, initiated until the age of 18 years

Inclusion Criteria (control group):

• Provide signed and dated informed consent form (additionally from guardian for participants aged under 18 years)
• Willing to comply with all study procedures and be available for the duration of the study
• Male
• Age between 16 and 49 years (no blood samples for participants aged under 18 years)
• Physiological and symmetric gait pattern without using aids or assistance

Exclusion Criteria:

• Subjects suffering from functional impairments caused by other conditions than hemophilia
• PWH with joint bleedings within 30 days prior to the examination (applies for test group only)
• PWH treated with immune-tolerance therapy and/or not successfully treated present or past high-titer factor VIII or FIX inhibitor (applies for test group only)

Test group population will be recruited at the clinical hemophilia center and pediatric unit of the Medical University of Vienna (patients with hemophila have biannual appointments)

Test group participants are asked to invite a friend at the same age (+/- 3 years; between 16 and 45y) to participate in the sense of a peer-matched control