Classification of the kinetics of factor VIII inhibitors in haemophilia A:plasma dilution studies are more discriminatory than time-course studies

Factor VIII inhibitors have previously been classified as type I or type II using complex experiments that study the time course of inactivation of fa ctor VIII and the effect of varying the antibody concentration. Classificat ion may be important to better understand inhibitor behaviour in vivo. To d etermine the most reliable method of classifying the kinetics of factor VII I inactivation, we studied 11 patients with haemophilia A, comprising five severe, three mild and three acquired cases, and compared the classificatio n obtained from plasma dilution studies and time-course studies. The plasma dilution studies showed two distinctly different patterns: a steep slope w ith complete FVIII:C inactivation at high antibody concentrations for type I inhibitors and a FVIII:C plateau with incomplete inactivation for type II inhibitors. Six type I (four severe, one mild and one acquired) and two ty pe II (one mild and one acquired) inhibitors were classified using either p lasma samples or purified and concentrated IgG, while the remaining were un determined owing to insufficient available plasma. In contrast, the time-co urse studies could not discriminate between these groups. We recommend that plasma dilution studies be used for the classification of in vitro kinetic s of factor VIII inhibitors.