CO-21 | FUSION 2: VALIDATION AND CLINICAL PERFORMANCE OF AN INTEGRATED ULTRASOUND–FUNCTIONAL ASSESSMENT SYSTEM IN HEMOPHILIA

M.E. Susi¹, E.A. Boccalandro², A. Giuffrida³, I. Ricca⁴, P. Imazio⁵, E. Bonetti⁶, I. Nichele⁷ B. Pollio⁸, E. Zanon⁹, E. Baldacci¹⁰, C. Santoro¹⁰, G. Delios⁴, S. Ligia¹⁰, M. Biglietto¹⁰, I. Calcaterra¹¹, M. Napolitano¹², M. Bodini², C. Simion⁹, B. Borsellino⁸, G. Pasta¹³, M.N.D. Di Minno¹¹, C. Martinoli^14|15 | ¹DIMES, Department of Experimental Medicine, University of Genoa, Italy; ²Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Fondazione Luigi Villa, Milano, Italy; ³Hemophilia Center, Borgo Roma Hospital, Integrated University Hospital of Verona, Italy; ⁴Immunology and Transfusion Medicine Service, Hemophilia Center, Ivrea Hospital, Local Health Authority TO4, Ivrea, Italy; ⁵Rehabilitation and Functional Recovery Service, Pediatric Orthopedics Unit, Regina Margherita Children’s Hospital, City of Health and Science University Hospital of Turin, Italy; ⁶Pediatric Oncohematology Unit, Borgo Trento Hospital, Integrated University Hospital of Verona, Italy; ⁷Haemophilia and Thrombosis Center, Haematology Department, San Bortolo Hospital, Vicenza, Italy; ⁸Transfusion Medicine and Immunohematology Service, Regina Margherita Children’s Hospital, City of Health and Science University Hospital of Turin, Italy; ⁹Coagulation Disorders and Hemophilia Center, University Hospital of Padova, Italy; ¹⁰Unit of Special Diagnosis and Therapy of Hemostasis and Thrombosis, Hematology Department, Policlinico Umberto I, Sapienza University of Rome, Italy; ¹¹Department of Clinical Medicine and Surgery, Regional Reference Centre for Coagulation Disorders, Federico II University, Napoli, Italy; ¹²Dipartimento PROMISE, Università degli Studi di Palermo and UOC Ematologia e Malattie Rare, PO “Cervello”, Palermo, Italy; ¹³Orthopedics and Traumatology Clinic, IRCCS Policlinico San Matteo Foundation, Pavia, Italy; ¹⁴DISSAL, Department of Health Sciences, University of Genoa, Italy; ¹⁵UOC Emergency and Musculoskeletal Radiology, IRCCS AOM San Martino Hospital, Genova, Italy

Background and Aims. FUSION (Functional & Ultrasound Integrated Observation in Hemophilia) is an integrated musculoskeletal assessment framework combining point-of-care ultrasound (HEAD-US) with a simplified functional evaluation. While ultrasound and clinical joint scores provide complementary information, the extent to which functional performance contributes independent information beyond established tools remains unclear. This study aimed to validate the FUSION composite score and investigate whether its functional component captures clinically relevant dimensions not explained by HEAD-US or Hemophilia Joint Health Score (HJHS) 2.1 alone.
Materials and Methods. We conducted a prospective multicenter cross-sectional study including 121 patients with hemophilia A, hemophilia B, or von Willebrand disease undergoing integrated assessment with HEAD-US, HJHS 2.1, and FUSION. The FUSION score combines HEAD-US evaluation of elbows, knees, and ankles with a weighted simplified functional score (F×4) derived from six standardized motor tasks. Convergent validity was assessed using Spearman correlation and Steiger’s z-test. Variance decomposition and residual analyses were performed to identify the proportion and nature of information uniquely captured by FUSION.
Results. FUSION showed strong convergent validity with HJHS (ρ=0.764, p<0.001), comparable to the correlation observed between HEAD-US and HJHS (ρ=0.776, p<0.001; Steiger p=0.82). However, the addition of the functional component significantly increased explained variance beyond HEAD-US alone (ΔR²=0.070, p<0.001), supporting an independent contribution of functional assessment. Variance decomposition demonstrated that 25.5% of the variance captured by FUSION was not explained by HJHS. Notably, 43.1% of the variance of the functional component (F×4) remained unexplained by HJHS, indicating that FUSION captures a substantial non-overlapping functional domain. Discordance analyses further supported the complementary role of FUSION. Among patients with HJHS=0, FUSION identified abnormalities in 53.8% of cases. In patients with HEAD-US=0, FUSION detected abnormalities in 55.0% versus 30.0% with HJHS alone (p=0.013), with all additional detections driven by the functional component.
Conclusions. FUSION preserves strong alignment with established hemophilia joint assessment tools while simultaneously identifying a substantial and clinically relevant functional domain not captured by HJHS or structural ultrasound evaluation alone. These findings support the concept of a multidimensional structural-functional assessment model and suggest that current joint-focused scores may underestimate global biomechanical and compensatory impairment in hemophilia.