title: The half-life of infused factor VIII is shorter in hemophiliac patients with blood group O than in those with blood group A.
abstract: A considerable inter-individual variation in half-life of infused factor VIII is observed among patients with hemophilia A. The factors contributing to this wide range in factor VIII half-life are not known in detail. We analysed the pharmacokinetics of infused factor VIII in 32 patients with hemophilia A, comprising 20 brothers from 10 families, 3 and 4 brothers from 2 families, and 5 patients from 5 single families, respectively. Multiple linear regression analysis was used to assess the effect of several variables on factor VIII half-life. We found that the pre-infusion von Willebrand factor antigen levels (vWF:Ag) were positively correlated with factor VIII half-life (r = 0.52, p = 0.002), i.e., each variable was associated with about 27% of the variance of the other. In fraternal pairs, familial clustering was significant for ABO blood group (p < 0.001), but could not be detected for factor VIII half-lives or pre-infusion vWF:Ag levels. vWF:Ag level (p = 0.001) and ABO blood group (p = 0.003) significantly determined factor VIII half-life, whereas age, length, bodyweight, the presence or absence of a factor VIII gene inversion, and Rhesus phenotype did not. Patients with blood group O exhibited a statistically significant shorter factor VIII half-life than patients with blood group A (15.3 versus 19.7 h, respectively) (p = 0.003). Patients with blood group A and O differ in respect to the presence of anti-A antibodies in the latter. It is possible that these anti-A antibodies interact with endogenous vWF, thus affecting the half-life time of the factor VIII/vWF complex.
authors.affiliation: The van Creveldkliniek, and The Department of Haematology, Graduate School of Biomembranes, University Medical Center Utrecht, The Netherlands. andre.vlot@wxs.nl
authors.forename: A J
authors.initials: AJ
authors.lastname: Vlot
authors.forename: E P
authors.initials: EP
authors.lastname: Mauser-Bunschoten
authors.forename: A G
authors.initials: AG
authors.lastname: Zarkova
authors.forename: E
authors.initials: E
authors.lastname: Haan
authors.forename: C L
authors.initials: CL
authors.lastname: Kruitwagen
authors.forename: J J
authors.initials: JJ
authors.lastname: Sixma
authors.forename: H M
authors.initials: HM
authors.lastname: van den Berg
mesh_terms: D000017:ABO Blood-Group System; D000328:Adult; D005169:Factor VIII / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006207:Half-Life; D006467:Hemophilia A / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D000017:ABO Blood-Group System; D005169:Factor VIII