title: Factor VIII half-life and clinical phenotype of severe hemophilia A.
abstract: OBJECTIVE
  Patients with severe hemophilia A have considerably different factor VIII half-lives. Whether this is associated with their clinical characteristics has not been reported. The aim of this study was to describe the association of factor VIII half-lives with treatment and clinical characteristics of patients with severe hemophilia A, who have been treated with individually tailored prophylaxis.
  
  
  METHODS
  Patients were selected from a single-center cohort of 214 patients with severe hemophilia, born between 1944 and 1995. To improve efficiency we measured factor VIII half-life in 42 patients selected from the extremes of the distribution of phenotypes of severe hemophilia. We assessed information on life-long joint bleeds and clotting factor consumption. Orthopedic outcome was assessed by the Pettersson score.
  
  
  RESULTS
  Among these patients with severe hemophilia, factor VIII half-life ranged from 7.4-20.4 hours (median 11.8 hours). A one-hour increase in factor VIII half-life was associated with 96 (95% confidence interval (CI) 2 -190) IU less clotting factor use per kg per year. Age was an important determinant of factor VIII half-life, and explained a large part of the association between factor VIII half-life and clotting factor consumption. The median number of joint bleeds per year and arthropathy were similar for patients with different half-lives.
  
  
  CONCLUSIONS
  Among patients with severe hemophilia, treated prophylactically with clotting factor, those with a shorter factor VIII half-life required slightly more clotting factor to prevent joint bleeds and subsequent arthropathy than similar patients with a longer factor VIII half-life.
authors.affiliation: Van Creveldkliniek, UMCU, Room C01.425 PO-Box 85500, 3508 GA Utrecht, The Netherlands. k.vandijk@azu.nl
authors.forename: Karin
authors.initials: K
authors.lastname: van Dijk
authors.forename: Johanna G
authors.initials: JG
authors.lastname: van der Bom
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Lenting
authors.forename: Philip G
authors.initials: PG
authors.lastname: de Groot
authors.forename: Eveline P
authors.initials: EP
authors.lastname: Mauser-Bunschoten
authors.forename: Goris
authors.initials: G
authors.lastname: Roosendaal
authors.forename: Diederick E
authors.initials: DE
authors.lastname: Grobbee
authors.forename: H Marijke
authors.initials: HM
authors.lastname: van den Berg
mesh_terms: D000328:Adult; D002675:Child, Preschool; D015331:Cohort Studies; D004334:Drug Administration Schedule; D005169:Factor VIII / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006207:Half-Life; D006467:Hemophilia A / Q000097:blood* / Q000517:prevention & control*; D006801:Humans
chemical_list: D005169:Factor VIII