title: Cross-reactivity to porcine factor VIII of factor VIII inhibitors in patients with haemophilia in Australia and New Zealand.
abstract: BACKGROUND
  Inhibitory antibodies which neutralise factor VIII develop in 10-20% of individuals with inherited haemophilia A and rarely as autoantibodies in normal individuals to cause acquired haemophilia. The antibodies are directed against human factor VIII but cross-react to varying degrees with porcine factor VIII. Porcine factor VIII can be used for treatment in individuals with low cross-reactivity.
  
  
  OBJECTIVE
  To determine the cross-reactivity of factor VIII inhibitors between human factor VIII and porcine factor VIII, in a population of patients with inherited and acquired haemophilia A. Also, to determine whether patients with inherited haemophilia and inhibitors have a higher incidence of factor VIII gene inversion in intron 22.
  
  
  METHODS
  Samples and data sheets from 43 patients with inherited and ten with acquired haemophilia were submitted from hospitals in Australia and New Zealand. Inhibitor levels to human and porcine factor VIII were measured by the Bethesda method in 39 with inherited and nine with acquired haemophilia A.
  
  
  RESULTS
  Of 39 patients with inherited haemophilia A, cross-reactivity was 0% in 17 patients, 1-19% in six, 20-39% in 11 and 40-80% in five. In six of nine patients with acquired haemophilia cross-reactivity was < or = 7%. In inherited severe haemophilia A, the frequency of the intron 22 inversion was not greater in 37 study patients than in 28 patients without an inhibitor.
  
  
  CONCLUSIONS
  Many patients in Australia and New Zealand with inhibitors to human factor VIII presently show a low or absent level of cross-reactivity to porcine factor VIII. These may respond to treatment with this concentrate at least in the short term. There remains a group of patients with high cross-reactivity who will respond only to recombinant factor VIIa or prothrombin complex concentrates.
authors.affiliation: Division of Haematology, Institute of Medical and Veterinary Science, Adelaide, SA.
authors.forename: J V
authors.initials: JV
authors.lastname: Lloyd
authors.forename: A M
authors.initials: AM
authors.lastname: Street
authors.forename: E
authors.initials: E
authors.lastname: Berry
authors.forename: J
authors.initials: J
authors.lastname: McPherson
authors.forename: H
authors.initials: H
authors.lastname: Ekert
authors.forename: A
authors.initials: A
authors.lastname: Lammi
authors.forename: W R
authors.initials: WR
authors.lastname: McWhirter
authors.forename: E M
authors.initials: EM
authors.lastname: Duncan
authors.forename: E L
authors.initials: EL
authors.lastname: Maxwell
authors.forename: J
authors.initials: J
authors.lastname: Rowell
authors.forename: R I
authors.initials: RI
authors.lastname: Baker
authors.forename: M F
authors.initials: MF
authors.lastname: Leahy
authors.forename: D
authors.initials: D
authors.lastname: Jupe
mesh_terms: D000818:Animals; D001315:Australia; D019774:Blood Coagulation Factor Inhibitors / Q000276:immunology*; D007446:Chromosome Inversion; D003429:Cross Reactions; D005169:Factor VIII / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use*; D006467:Hemophilia A / Q000628:therapy*; D006801:Humans; D009520:New Zealand; D012720:Severity of Illness Index; D013552:Swine
chemical_list: D019774:Blood Coagulation Factor Inhibitors; D005169:Factor VIII