Factor VIII Antibodies Demonstrate Type I or Type II Kinetics in Acquired Haemophilia A

Acquired haemophilia A (AHA) is an acquired bleeding disorder resulting from autoantibodies against Factor VIII (FVIII). Previous studies have reported differences in FVIII inhibitor kinetics (type I or type II) in AHA compared to severe haemophilia A.

To characterise inhibitor kinetics in AHA and evaluate the proportions displaying type I, II or indeterminate kinetics.

Single-centre retrospective study of inhibitor kinetics in adults with AHA. Type I kinetics were defined as linear FVIII inhibition with ≥ 97% FVIII inactivation. Type II kinetics were defined as non-linear kinetics and inability to completely neutralise FVIII. Inhibitor titres were calculated using two methods outlined by the International Council for Standardisation in Haematology.

Baseline samples from 34 patients were included. Fifteen samples (44.1%) exhibited type I kinetics, 16 samples (47.1%) exhibited type II kinetics and 3 (8.8%) were indeterminate. Plateau mean residual FVIII:C was higher for inhibitors displaying type II compared to type I kinetics (18.6 vs. 2.9 IU/dL, p < 0.0001). Non-linear regression using a dose-response curve without categorisation for kinetics type yielded a poor fit (R² = 38%), which improved with refitting using categories of type I or II kinetics that explained 87% and 85% of the variability. The median difference in inhibitor titre between the two reporting methods was 5% and 15% in the type I and II kinetics groups, respectively.

FVIII autoantibodies demonstrate either type I or type II kinetics. Greater discrepancy in reported inhibitor titres depending on the method used is seen for inhibitors with type II kinetics.