title: Bleeding prophylaxis for major surgery in patients with type 2 von Willebrand disease with an intermediate purity factor VIII-von Willebrand factor concentrate (Haemate-P).
abstract: The parameters to diagnose von Willebrand disease (vWD) include factor VIII coagulant activity (FVIII:C), von Willebrand factor antigen (vWF:Ag), von Willebrand factor ristocetin cofactor activity (vWF:RCo), and von Willebrand factor collagen binding activity (vWF:CB). Type 2 vWD is associated with a moderate bleeding diathesis due to low levels of vWF:RCo and vWF:CB as compared with near normal or normal values for FVIII:C and vWF:Ag. As the factor VIII/von Willebrand factor (vWF) concentrate, Haemate-P, is featured by a vWF:RCo/FVIII:C ratio of about 2.2, the recommended loading dose of 50 U/kg FVIII:C followed by 25 U/kg FVIII:C every 12 h for several days for bleeding prophylaxis in type 2 vWD patients undergoing major surgery demonstrated a predicted significant over-treatment reaching vWF:RCo levels above 2 U/ml. Therefore, we restricted Haemate-P substitution for major surgery to one loading dose of 40-50 U/kg FVIII:C (88-110 U/kg vWF:RCo) followed by 15-20 U/kg FVIII:C (33-44 U/kg vWF:RCo) every 12 h for several days and evaluated this strategy in a prospective pharmacokinetic and efficacy study for bleeding prophylaxis in five type 2 vWD patients. Pre-treatment and peak levels (1 h after Haemate-P loading dose) rose from 0.43-0.66 to 1.5-2.5 U/ml for FVIII:C, from 0.23-0.45 to 1.5-2.5 U/ml for vWF:Ag, from 0.10-< 0.20 to 1.5-2.5 U/ml for vWF:RCo, and from < 0.05-0.10 to 1.0-2.0 U/ml for vWF:CB. Mean in vivo recoveries per transfused IU FVIII:C/kg body weight were 3.2% for FVIII:C, 3.9% for vWF:RCo, and 2.8% for vWF:CB. Mean in vivo recoveries per transfused IU vWF:RCo/kg were 1.45% for FVIII:C, 1.7% for vWF:RCo and 1.25% for vWF:CB. The biological half-life times after transfused Haemate-P were about 12 h for both vWF:RCo and vWF:CB. Based on these pharmacokinetic data, we propose to adapt the loading dose factor VIII/vWF concentrate (Haemate-P) to 60-80 U/kg vWF:RCo followed by 30-40 U/kg vWF:RCo every 12 h for no longer than several days (less than 1 week) for bleeding prophylaxis during major surgery or trauma, and to one loading dose of 40-60 U/kg vWF:RCo for minor surgery, trauma or mucotaneous bleedings in patients with type 2 vWD unresponsive to DDAVP.
authors.affiliation: Haemostasis and Thrombosis Research, Department of Haematology, Antwerp University Hospital, University of Antwerp, Belgium. jan.michiels@uza.be
authors.forename: Jan Jacques
authors.initials: JJ
authors.lastname: Michiels
authors.forename: Zwi N
authors.initials: ZN
authors.lastname: Berneman
authors.forename: Marc
authors.initials: M
authors.lastname: van der Planken
authors.forename: Wilfried
authors.initials: W
authors.lastname: Schroyens
authors.forename: Ulrich
authors.initials: U
authors.lastname: Budde
authors.forename: Huub H D M
authors.initials: HH
authors.lastname: van Vliet
mesh_terms: D000328:Adult; D016063:Blood Loss, Surgical / Q000517:prevention & control*; D001835:Body Weight; D004338:Drug Combinations; D005169:Factor VIII / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005260:Female; D006470:Hemorrhage / Q000517:prevention & control*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019990:Perioperative Care; D017410:Practice Guidelines as Topic; D011446:Prospective Studies; D012189:Retrospective Studies; D016896:Treatment Outcome; D014842:von Willebrand Diseases / Q000628:therapy*; D014841:von Willebrand Factor / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D004338:Drug Combinations; D014841:von Willebrand Factor; D005169:Factor VIII