Arthroplasty After Hemophilia Gene Therapy: Perioperative Implications and Clinical Experience

INTRODUCTION: Gene therapy can provide sustained endogenous factor VIII (FVIII) or factor IX (FIX) expression, creating a perioperative phenotype that differs from both conventionally treated severe hemophilia and routine arthroplasty patients. Evidence for major joint replacement after gene therapy remains limited. AIM: To synthesize current clinical evidence on arthroplasty after hemophilia gene therapy and define practical implications for hemostatic management, venous thromboembolism (VTE) prevention, rehabilitation, and multidisciplinary planning. METHODS: PubMed/MEDLINE and reference lists were searched through September 2026 for direct arthroplasty reports, invasive-procedure studies after gene therapy, and current guidance relevant to surgery and thromboprophylaxis. RESULTS: Published evidence includes dedicated total knee and total hip arthroplasty reports, trial-level arthroplasty observations, and broader invasive-procedure datasets after valoctocogene roxaparvovec, etranacogene dezaparvovec, and fidanacogene elaparvovec. These data show that gene therapy may substantially reduce exogenous factor requirements, but they do not establish a validated FVIII or FIX threshold for arthroplasty. Current World Federation of Hemophilia guidance recommends achieving procedure-appropriate factor levels, with supplemental clotting factor concentrate when necessary. In patients whose factor activity has shifted toward mild-deficiency or nonhemophilic levels, standard arthroplasty VTE-prevention principles should not be withheld solely because of the historical diagnosis of hemophilia. CONCLUSION: Arthroplasty after hemophilia gene therapy should be managed as phenotype-based major surgery: procedure-appropriate hemostasis, immediate rescue-factor access, serial postoperative monitoring, and appropriately timed VTE prophylaxis remain essential.