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 factor VIII and the effect of varying the antibody concentration. Classification may be important to better understand inhibitor behaviour in vivo. To determine the most reliable method of classifying the kinetics of factor VIII inactivation, we studied 11 patients with haemophilia A, comprising five severe, three mild and three acquired cases, and compared the classification obtained from plasma dilution studies and time-course studies. The plasma dilution studies showed two distinctly different patterns: a steep slope with 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 type II (one mild and one acquired) inhibitors were classified using either plasma samples or purified and concentrated IgG, while the remaining were undetermined owing to insufficient available plasma. In contrast, the time-course studies could not discriminate between these groups. We recommend that plasma dilution studies be used for the classification of in vitro kinetics of factor VIII inhibitors.