Molecular defects in coagulation Factor VIII and their impact on Factor VIII function.

ABSTRACT

Molecular defects in Factor VIII (FVIII), such as haemophilia A-related mutations or denaturative conformational changes, may affect the stability of FVIII as well as its interactions with physiological activators, von Willebrand Factor, phospholipid, or conformationally sensitive antibodies. We summarize the contemporary assays which allow identification of impaired functional interactions of FVIII that cause a reduction or loss of its cofactor activity and/or increased immunogenicity. These assays can potentially be used for detection of molecular defects in FVIII and elucidation of the function impaired by these defects.