Terminal half?life of FVIII and FIX according to age, blood group and concentrate type: Data from the WAPPS database


Real-life data on pharmacokinetics of factor (F) VIII/IX concentrates, especially extended half-life (EHL), concentrates in large cohorts of persons with hemophilia are currently lacking.


This cross-sectional study aimed to establish reference values for terminal half-life (THL) for FVIII/IX concentrates according to concentrate type, age, blood group and inhibitor history.


Data were extracted from the Web-Accessible Population Pharmacokinetics Service database. Groups were compared by nonparametric tests. THL was modelled according to patient characteristics and concentrate type.


Infusion data (n = 8022) were collected from 4832 subjects (including 2222 children) with severe hemophilia (age: 1 month–85 years; 89% hemophilia A; 34% using EHL concentrates, 9.8% with history of inhibitors). THL of FVIII-EHL was longer than of FVIII standard half-life (SHL; median 15.1 vs. 11.1 h). FVIII-THL was dependent on age, concentrate type, blood group, and inhibitor history. THL of FIX-EHL was longer than of FIX-SHL (median 106.9 vs. 36.5 h). FIX-THL increased with age until 30 years and remained stable thereafter. FVIII-THL was shorter in subjects with blood group O. THL was decreased by 1.3 h for FVIII and 22 h for FIX in subjects with a positive inhibitor history.


We established reference values for FVIII/IX concentrates according to patient characteristics and concentrate type in a large database of hemophilia patients. These reference values may inform clinical practice (e.g., assessment of immune tolerance success), economic implications of procurement processes and value attribution of novel treatments (e.g., mimetics, gene therapy).