Surgical outcomes in people with hemophilia A taking emicizumab prophylaxis: experience from the HAVEN 1-4 studies

Authors: Kruse-Jarres, R; Peyvandi, F; Oldenburg, J; Chang, T; Chebon, S; Doral, MY; Croteau, SE; Lambert, T; Kempton, CL; Pipe, SW; Ko, RH; Trzaskoma, B; Dhalluin, C; Bienz, NS; Niggli, M; Lehle, M; Paz-Priel, I; Young, G; Jimenez-Yuste, V

Affiliations: Washington Ctr Bleeding Disorders, Seattle, WA USA. Univ Washington, Div Hematol, Seattle, WA USA. Fdn IRCCS Ca Granda Osped Maggiore Policlin, Angelo Bianchi Bonomi Hemophilia, Milan, Italy. Thrombosis Ctr, Milan, Italy. Univ Milan, Dept Pathophysiol & Transplantat, Milan, Italy. Univ Clin Bonn, Bonn, Germany. Genentech Inc, San Francisco, CA USA. F Hoffmann La Roche Ltd, Basel, Switzerland. Boston Childrens Hosp, Boston Hemophilia Ctr, Boston, MA USA. Bicetre AP HP Hosp, Fac Med Paris 11, Haemophilia Care Ctr, Paris, France. Emory Univ, Dept Hematol & Med Oncol, Sch Med, Atlanta, GA USA. Univ Michigan, Ann Arbor, MI USA. Univ Southern Calif, Childrens Hosp Los Angeles, Keck Sch Med, Los Angeles, CA USA. Univ Autonoma Madrid, La Paz Hosp, Madrid, Spain

Publication: Blood Advances.; 2022; 6. 6140–6150

Abstract: Many people with hemophilia A (PwHA) undergo surgery in their lifetime, often because of complications of their disease. Emicizumab is the first bispecific monoclonal antibody prophylactic therapy for PwHA, and its efficacy and safety have been previously demonstrated; however, there is a need to build an evidence base on the management of PwHA on emicizumab undergoing surgery. Data from the HAVEN 1-4 phase 3 clinical trials were pooled to provide a summary of all minor and major surgeries in PwHA with or without factor VIII (FVIII) inhibitors who were receiving emicizumab prophylaxis. Overall, 233 surgeries were carried out during the HAVEN 1-4 trials: 215 minor surgeries (including minor dental and joint procedures, central venous access device placement or removal, and endoscopies) in 115 PwHA (64 with FVIII inhibitors) and 18 major surgeries (including arthroplasty and synovectomy) in 18 PwHA (10 with FVIII inhibitors). Perioperative hemostatic support was at the discretion of the treating physician. Overall, the median (interquartile range [IQR]) age was 33.5 (13.0-49.0) years and the median (IQR) emicizumab exposure time before surgery was 278.0 (177.0-431.0) days. Among the 215 minor surgeries, 141 (65.6%) were managed without additional prophylactic factor concentrate, and of those, 121 (85.8%) were not associated with a postoperative bleed. The majority (15 of 18 [83.3%]) of major surgeries were managed with additional prophylactic factor concentrate. Twelve (80.0%) of these 15 surgeries were associated with no intraoperative or postoperative bleeds. The data demonstrate that minor and major surgeries can be performed safely in PwHA receiving emicizumab prophylaxis.