Long-term risk factors for hemophilic arthropathy in patients with severe hemophilia A: a 36-year retrospective cohort study
- 1Department of Orthopedics, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi, Kitakyushu, 8078555 Japan
- 2Department of Environmental Epidemiology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi, Kitakyushu, 8078555 Japan
- 3Department of Pediatrics, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi, Kitakyushu, 8078555 Japan
Abstract
Background: Hemophilic arthropathy (HA) is a major cause of disability in patients with severe hemophilia A. However, long-term data describing progression to advanced radiographic HA across major joint sites remain limited. We investigated risk factors for progression to advanced HA over extended follow-up.
Methods: We conducted a retrospective cohort study of inhibitor-negative patients with severe hemophilia A followed at our institute between 1984 and 2020. Bilateral elbows, knees, and ankles were evaluated (six joints per patient). HA progression was defined as reaching Arnold–Hilgartner stage ≥ IV. Time to progression was analyzed using Cox proportional hazards models with cluster-robust standard errors, with participant as the clustering variable, to account for within-participant correlation across joints. Covariates included joint site, Arnold–Hilgartner stage at initiation of regular prophylaxis, age at first visit to our institute, prophylaxis status at the first visit, and laterality.
Results: The cohort included 109 patients (mean age at first visit to our institute, 14.3 years). At the first visit, Arnold–Hilgartner stage ≥ I changes were present in 15% of elbows (29/200), 8% of knees (16/200), and 27% of ankles (51/186). Across 583 joints and 8,634 joint-years of follow-up, 94 joints progressed to stage ≥ IV (10.9 per 1,000 joint-years of follow-up). In multivariable analysis, baseline radiographic status at the start of regular prophylaxis was strongly associated with progression (vs stage 0: stage I HR 14.95; stage II HR 11.84; stage III HR 34.47). Patients already receiving regular prophylaxis at the first visit had a lower risk of progression (HR 0.54). After adjustment, joint-site differences were not evident, and the independent association of age at first visit to our institute with progression was not estimated with sufficient precision.
Conclusions: Baseline radiographic status at initiation of regular prophylaxis was strongly associated with long-term progression to advanced radiographic HA. These findings support initiating regular prophylaxis before radiographic joint changes become established.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12891-026-10343-9.
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BibTeX
@article{suzuki2026longterm,
title = {{Long-term risk factors for hemophilic arthropathy in patients with severe hemophilia A: a 36-year retrospective cohort study}},
author = {Hitoshi Suzuki and Yoshihisa Fujino and Rie Shirayama and Takafumi Tajima and Yoshiaki Yamanaka and Kotaro Tokuda and Manabu Tsukamoto and Tomoya Arashi and Reiji Fukano and Akinori Sakai},
journal = {BMC Musculoskeletal Disorders},
year = {2026},
month = aug,
doi = {10.1186/s12891-026-10343-9},
url = {https://doi.org/10.1186/s12891-026-10343-9},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Long-term risk factors for hemophilic arthropathy in patients with severe hemophilia A: a 36-year retrospective cohort study
AU - Hitoshi Suzuki
AU - Yoshihisa Fujino
AU - Rie Shirayama
AU - Takafumi Tajima
AU - Yoshiaki Yamanaka
AU - Kotaro Tokuda
AU - Manabu Tsukamoto
AU - Tomoya Arashi
AU - Reiji Fukano
AU - Akinori Sakai
PY - 2026
DA - 2026/08/08
JO - BMC Musculoskeletal Disorders
DO - 10.1186/s12891-026-10343-9
UR - https://doi.org/10.1186/s12891-026-10343-9
AB - Background: Hemophilic arthropathy (HA) is a major cause of disability in patients with severe hemophilia A. However, long-term data describing progression to advanced radiographic HA across major joint sites remain limited. We investigated risk factors for progression to advanced HA over extended follow-up. Methods: We conducted a retrospective cohort study of inhibitor-negative patients with severe hemophilia A followed at our institute between 1984 and 2020. Bilateral elbows, knees, and ankles were evaluated (six joints per patient). HA progression was defined as reaching Arnold–Hilgartner stage ≥ IV. Time to progression was analyzed using Cox proportional hazards models with cluster-robust standard errors, with participant as the clustering variable, to account for within-participant correlation across joints. Covariates included joint site, Arnold–Hilgartner stage at initiation of regular prophylaxis, age at first visit to our institute, prophylaxis status at the first visit, and laterality. Results: The cohort included 109 patients (mean age at first visit to our institute, 14.3 years). At the first visit, Arnold–Hilgartner stage ≥ I changes were present in 15% of elbows (29/200), 8% of knees (16/200), and 27% of ankles (51/186). Across 583 joints and 8,634 joint-years of follow-up, 94 joints progressed to stage ≥ IV (10.9 per 1,000 joint-years of follow-up). In multivariable analysis, baseline radiographic status at the start of regular prophylaxis was strongly associated with progression (vs stage 0: stage I HR 14.95; stage II HR 11.84; stage III HR 34.47). Patients already receiving regular prophylaxis at the first visit had a lower risk of progression (HR 0.54). After adjustment, joint-site differences were not evident, and the independent association of age at first visit to our institute with progression was not estimated with sufficient precision. Conclusions: Baseline radiographic status at initiation of regular prophylaxis was strongly associated with long-term progression to advanced radiographic HA. These findings support initiating regular prophylaxis before radiographic joint changes become established. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12891-026-10343-9.
SN - 1471-2474
ER -