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

BACKGROUND: 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. OBJECTIVES: This cross‐sectional study aimed to establish reference values for terminal half‐life (T...

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Autores principales: Versloot, Olav, Iserman, Emma, Chelle, Pierre, Germini, Federico, Edginton, Andrea N., Schutgens, Roger E. G., Iorio, Alfonso, Fischer, Kathelijn
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8361743/
https://www.ncbi.nlm.nih.gov/pubmed/34013558
http://dx.doi.org/10.1111/jth.15395
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author Versloot, Olav
Iserman, Emma
Chelle, Pierre
Germini, Federico
Edginton, Andrea N.
Schutgens, Roger E. G.
Iorio, Alfonso
Fischer, Kathelijn
author_facet Versloot, Olav
Iserman, Emma
Chelle, Pierre
Germini, Federico
Edginton, Andrea N.
Schutgens, Roger E. G.
Iorio, Alfonso
Fischer, Kathelijn
author_sort Versloot, Olav
collection PubMed
description BACKGROUND: 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. OBJECTIVES: 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. PATIENTS/METHODS: 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. RESULTS: 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. CONCLUSIONS: 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).
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spelling pubmed-83617432021-08-17 Terminal half‐life of FVIII and FIX according to age, blood group and concentrate type: Data from the WAPPS database Versloot, Olav Iserman, Emma Chelle, Pierre Germini, Federico Edginton, Andrea N. Schutgens, Roger E. G. Iorio, Alfonso Fischer, Kathelijn J Thromb Haemost HAEMOSTASIS BACKGROUND: 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. OBJECTIVES: 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. PATIENTS/METHODS: 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. RESULTS: 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. CONCLUSIONS: 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). John Wiley and Sons Inc. 2021-06-18 2021-08 /pmc/articles/PMC8361743/ /pubmed/34013558 http://dx.doi.org/10.1111/jth.15395 Text en © 2021 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle HAEMOSTASIS
Versloot, Olav
Iserman, Emma
Chelle, Pierre
Germini, Federico
Edginton, Andrea N.
Schutgens, Roger E. G.
Iorio, Alfonso
Fischer, Kathelijn
Terminal half‐life of FVIII and FIX according to age, blood group and concentrate type: Data from the WAPPS database
title Terminal half‐life of FVIII and FIX according to age, blood group and concentrate type: Data from the WAPPS database
title_full Terminal half‐life of FVIII and FIX according to age, blood group and concentrate type: Data from the WAPPS database
title_fullStr Terminal half‐life of FVIII and FIX according to age, blood group and concentrate type: Data from the WAPPS database
title_full_unstemmed Terminal half‐life of FVIII and FIX according to age, blood group and concentrate type: Data from the WAPPS database
title_short Terminal half‐life of FVIII and FIX according to age, blood group and concentrate type: Data from the WAPPS database
title_sort terminal half‐life of fviii and fix according to age, blood group and concentrate type: data from the wapps database
topic HAEMOSTASIS
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8361743/
https://www.ncbi.nlm.nih.gov/pubmed/34013558
http://dx.doi.org/10.1111/jth.15395
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