title: von Willebrand factor/factor VIII concentrate (Humate-P) for management of elective surgery in adults and children with von Willebrand disease.
abstract: von Willebrand disease (VWD) is the most common inherited bleeding disorder. Treatment guidelines recommend the use of von Willebrand factor/factor VIII (VWF/FVIII) concentrate for VWD patients with type 2 or 3 VWD undergoing surgery, and type 1 patients undergoing surgery who are unresponsive, or for whom desmopressin acetate is contraindicated. This prospective, open-label, multinational study evaluated the safety, efficacy and optimal dosing of a VWF/FVIII concentrate (Humate-P) in subjects with VWD undergoing elective surgery. Dosing was based on VWF ristocetin cofactor (VWF:RCo) and FVIII pharmacokinetic assessments performed before surgery. Pharmacokinetic assessments were completed in 33 adults and 9 children. Haemostatic efficacy was assessed on a 4-point scale (excellent, good, moderate/poor or none). Overall effective haemostasis was achieved in 32/35 subjects. Median terminal VWF:RCo half-life was 11.7 h, and median incremental in vivo recovery was 2.4 IU dL(-1) per IU kg(-1) infused. Major haemorrhage occurred after surgery in 3/35 cases despite achieving target VWF and FVIII levels. Median VWF/FVIII concentrate loading doses ranged from 42.6 IU VWF:RCo kg(-1) (oral surgery) to 61.2 IU VWF:RCo kg(-1) (major surgery), with a median of 10 (range, 2-55) doses administered per subject. Adverse events considered possibly treatment-related (n = 6) were generally mild and of short duration. The results indicate that this VWF/FVIII concentrate is safe and effective in the prevention of excessive bleeding during and after surgery in individuals with VWD.
authors.affiliation: Comprehensive Center for Bleeding Disorders, Blood Center of Wisconsin, Medical College of Wisconsin, Milwaukee, WI 53226, USA. joan.gill@bcw.edu
authors.forename: J C
authors.initials: JC
authors.lastname: Gill
authors.forename: A
authors.initials: A
authors.lastname: Shapiro
authors.forename: L A
authors.initials: LA
authors.lastname: Valentino
authors.forename: J
authors.initials: J
authors.lastname: Bernstein
authors.forename: C
authors.initials: C
authors.lastname: Friedman
authors.forename: W L
authors.initials: WL
authors.lastname: Nichols
authors.forename: M
authors.initials: M
authors.lastname: Manco-Johnson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016063:Blood Loss, Surgical / Q000517:prevention & control*; D002648:Child; D002675:Child, Preschool; D003029:Coagulants / Q000008:administration & dosage*; D017558:Elective Surgical Procedures / Q000379:methods; D005169:Factor VIII / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D011182:Postoperative Care; D011300:Preoperative Care; D011446:Prospective Studies; D055815:Young Adult; D014842:von Willebrand Diseases / Q000188:drug therapy*; D014841:von Willebrand Factor / Q000008:administration & dosage*
chemical_list: D003029:Coagulants; D014841:von Willebrand Factor; C078147:F8 protein, human; D005169:Factor VIII