Eight-Week Resistance Training and Manual Therapy in Young Patients with Severe Hemophilia: A Case Series Evaluating Functional, Imaging, and Immunological Outcomes

<b>Background</b>: Hemophilia A and B are hereditary bleeding disorders that result in recurrent joint and muscle hemorrhages, leading to hemophilic arthropathy, muscle atrophy, and disability. Recent evidence suggests that physiotherapeutic interventions, including resistance training and manual therapy, may mitigate these effects, although comprehensive studies remain limited. This case series aimed to describe the outcomes of an eight-week physiotherapy program combining progressive resistance training and manual therapy in four adolescent boys (aged 11-17 years) with severe hemophilia. <b>Methods</b>: The program targeted joint function, muscle strength, ultrasound findings, and pain, with additional exploratory evaluation of neuroinflammatory and endothelial biomarkers: interleukin-18 (IL-18), C-C motif chemokine ligand 2 (CCL2), soluble intercellular adhesion molecule-1 (ssICAM-1), β-nerve growth factor (β-NGF), and soluble receptor for advanced glycation end-products (sRAGE). <b>Results</b>: After the intervention, Hemophilia Joint Health Score (HJHS) total scores decreased by 35-62%, indicating functional improvement, while muscle strength increased across most joints. No progression of arthropathy was observed on ultrasound (HEAD-US). IL-18 and ssICAM-1 levels decreased on average by 42% and 29%, respectively, whereas β-NGF and sRAGE increased by 39% and 11%, suggesting potential anti-inflammatory and neuroprotective responses. <b>Conclusions</b>: These descriptive findings indicate that individualized physiotherapy may serve as a supportive component of hemophilia care, while biomarker monitoring provides exploratory insight into treatment-related physiological responses.