title: Surgical evaluation of a recombinant factor VIII prepared using a plasma/albumin-free method: efficacy and safety of Advate in previously treated patients.
abstract: Evaluation of factor F(V)III replacement in patients with haemophilia A undergoing surgery is critical for FVIII concentrates, yet large scale, multi-center prospective studies, particularly using continuous infusion, are generally lacking for new products. This study evaluated efficacy and safety of a newly developed recombinant FVIII (rAHF-PFM) administered by bolus or continuous infusion in haemophilia A patients undergoing surgery. Subjects > or =5 years of age with baseline FVIII:C < or =2%, and > or =150 prior FVIII exposure days were included in this prospective, international, open-label, uncontrolled clinical trial. rAHF-PFM was administered perioperatively by bolus infusion (BI) or continuous infusion (CI) according to the standard use at the center to prevent bleeding complication. Both the surgeon and haematologist rated efficacy during hospitalization. Fifty-eight subjects underwent 65 surgical procedures (22 major haemorrhagic risk; 35 minor, 8 dental procedures). Bolus infusion was used exclusively in 47 procedures and continuous infusion, with or without supplemental bolus infusions, in 18. Haemostatic efficacy was assessed as excellent or good for 100% of intraoperative ratings (17 CI, 44 BI, 61 total procedures), and 100% of postoperative ratings performed at time of discharge (18 CI, 44 BI, 62 total procedures). Median total consumption of rAHF-PFM during hospitalization was 822 IU/kg/surgery with CI and 910 IU/kg/surgery with BI. Overall rAHF-PFM was well tolerated, and FVIII inhibitors were not detected. In conclusion, rAHF-PFM administered via continuous infusion or bolus injections is safe, non-immunogenic, and effective for perioperative hemostatic management in previously treated haemophilia A patients.
authors.affiliation: Hôpital Edouard Herriot, Centre Régional de Traitement de l'Hémophilie, Pavillon E, Place d'Arsonval, Lyon, France. claude.negrier@chu-lyon.fr
authors.forename: Claude
authors.initials: C
authors.lastname: Négrier
authors.forename: Amy
authors.initials: A
authors.lastname: Shapiro
authors.forename: Erik
authors.initials: E
authors.lastname: Berntorp
authors.forename: Ingrid
authors.initials: I
authors.lastname: Pabinger
authors.forename: Michael
authors.initials: M
authors.lastname: Tarantino
authors.forename: Antonio
authors.initials: A
authors.lastname: Retzios
authors.forename: Phillip
authors.initials: P
authors.lastname: Schroth
authors.forename: Bruce
authors.initials: B
authors.lastname: Ewenstein
mesh_terms: D000293:Adolescent; D016063:Blood Loss, Surgical / Q000517:prevention & control*; D002648:Child; D002675:Child, Preschool; D005169:Factor VIII / Q000008:administration & dosage* / Q000009:adverse effects*; D006467:Hemophilia A / Q000150:complications / Q000188:drug therapy*; D006487:Hemostasis / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D019106:Postoperative Hemorrhage / Q000517:prevention & control*; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: C078147:F8 protein, human; D005169:Factor VIII