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

Abstract

Severe hemophilia A (HA) patients develop inhibitory alloantibodies to factor VIII:C and therefore require bypass agents that are scarce, expensive and may provoke secondary effects. Twenty-three severe HA patients who were high-responders to FVIII inhibitors were studied. FVIII:C activity in plasma was measured by one-stage activated partial thromboplastin time method, and the quantification of FVIII:C inhibitors was carried out by the Nijmegen-Bethesda method. Inhibition kinetics was assessed through serial plasma dilutions. FVIII:C activity was <1% in all patients. Kinetics behavior of the inhibitors was classified as type I in 14 patients, type II in four and an intermediate pattern that we named type III in one case. We were unable to apply the regression model to the remaining four of 23 patients in the study because of their low inhibitory titer (<3 Nijmegen-Bethesda units per ml). Seventy-eight percent of the patients with inhibitor type I did not respond to high doses of FVIII therapy, whereas 50% of patients with type II kinetics did (P = 0.5323). Generally, patients belonging to the same family had similar kinetics behavior as well as concordant treatment response. Although nonsignificant, our results suggest an association between kinetics behavior and treatment response that may be a valuable prognostic parameter for the management of these patients.