Arthroplasty After Hemophilia Gene Therapy: Perioperative Implications and Clinical Experience

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.

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.

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.

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.

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.