Kinetics of factor VIII:C inhibitors and treatment response in severe hemophilia A patients

SUMMARY Severe hemophilia A (HA) patients develop inhibitory alloantibodies tofactor VIII:C and therefore require bypass agents that are scarce,expensive and may provoke secondary effects. Twenty-three severe HApatients who were high-responders to FVIII inhibitors were studied.FVIII:C activity in plasma was measured by one-stage activated partialthromboplastin time method, and the quantification of FVIII:Cinhibitors was carried out by the Nijmegen–Bethesda method. Inhibi-tion kinetics was assessed through serial plasma dilutions. FVIII:Cactivity was <1% in all patients. Kinetics behavior of the inhibitors wasclassified as type I in 14 patients, type II in four and an intermediatepattern that we named type III in one case. We were unable to applythe regression model to the remaining four of 23 patients in the studybecause of their low inhibitory titer (<3 Nijmegen–Bethesda units perml). Seventy-eight percent of the patients with inhibitor type I did notrespond to high doses of FVIII therapy, whereas 50% of patients withtype II kinetics did (P = 0.5323). Generally, patients belonging to thesame family had similar kinetics behavior as well as concordanttreatment response. Although nonsignificant, our results suggest anassociation between kinetics behavior and treatment response that maybe a valuable prognostic parameter for the management of thesepatients.