Factor VIII gene (F8) mutation and risk of inhibitor development in nonsevere hemophilia A
(2013) In Blood 122(11). p.1954-1962- Abstract
- Neutralizing antibodies (inhibitors) toward factor VIII form a severe complication in nonsevere hemophilia A, profoundly aggravating the bleeding pattern. Identification of high-risk patients is hampered by lack of data that take exposure days to therapeutic factor VIII concentrates into account. In the INSIGHT study, we analyzed the association between F8 mutation and inhibitor development in patients with nonsevere hemophilia A (factor VIII 2-40 IU/dL). This analysis included 1112 nonsevere hemophilia A patients from 14 centers in Europe and Australia that had genotyped at least 70% of their patients. Inhibitor risk was calculated as Kaplan-Meier incidence with cumulative number of exposure days as the time variable. During 44 800... (More)
- Neutralizing antibodies (inhibitors) toward factor VIII form a severe complication in nonsevere hemophilia A, profoundly aggravating the bleeding pattern. Identification of high-risk patients is hampered by lack of data that take exposure days to therapeutic factor VIII concentrates into account. In the INSIGHT study, we analyzed the association between F8 mutation and inhibitor development in patients with nonsevere hemophilia A (factor VIII 2-40 IU/dL). This analysis included 1112 nonsevere hemophilia A patients from 14 centers in Europe and Australia that had genotyped at least 70% of their patients. Inhibitor risk was calculated as Kaplan-Meier incidence with cumulative number of exposure days as the time variable. During 44 800 exposure days (median, 24 exposure days per patient; interquartile range [IQR], 7-90), 59 of the 1112 patients developed an inhibitor; cumulative incidence of 5.3% (95% confidence interval [CI], 4.0-6.6) after a median of 28 exposure days (IQR, 12-71). The inhibitor risk at 50 exposure days was 6.7% (95% CI, 4.5-8.9) and at 100 exposure days the risk further increased to 13.3% (95% CI, 9.6-17.0). Among a total of 214 different F8 missense mutations 19 were associated with inhibitor development. These results emphasize the importance of F8 genotyping in nonsevere hemophilia A. (Less)
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- author
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Blood
- volume
- 122
- issue
- 11
- pages
- 1954 - 1962
- publisher
- American Society of Hematology
- external identifiers
-
- wos:000324570900019
- scopus:84887363261
- pmid:23926300
- ISSN
- 1528-0020
- DOI
- 10.1182/blood-2013-02-483263
- language
- English
- LU publication?
- yes
- id
- 5e409e1b-0df1-4da6-9238-fe05b1b9ec96 (old id 4098990)
- date added to LUP
- 2016-04-01 10:40:44
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- 2022-04-04 20:11:14
@article{5e409e1b-0df1-4da6-9238-fe05b1b9ec96,
abstract = {{Neutralizing antibodies (inhibitors) toward factor VIII form a severe complication in nonsevere hemophilia A, profoundly aggravating the bleeding pattern. Identification of high-risk patients is hampered by lack of data that take exposure days to therapeutic factor VIII concentrates into account. In the INSIGHT study, we analyzed the association between F8 mutation and inhibitor development in patients with nonsevere hemophilia A (factor VIII 2-40 IU/dL). This analysis included 1112 nonsevere hemophilia A patients from 14 centers in Europe and Australia that had genotyped at least 70% of their patients. Inhibitor risk was calculated as Kaplan-Meier incidence with cumulative number of exposure days as the time variable. During 44 800 exposure days (median, 24 exposure days per patient; interquartile range [IQR], 7-90), 59 of the 1112 patients developed an inhibitor; cumulative incidence of 5.3% (95% confidence interval [CI], 4.0-6.6) after a median of 28 exposure days (IQR, 12-71). The inhibitor risk at 50 exposure days was 6.7% (95% CI, 4.5-8.9) and at 100 exposure days the risk further increased to 13.3% (95% CI, 9.6-17.0). Among a total of 214 different F8 missense mutations 19 were associated with inhibitor development. These results emphasize the importance of F8 genotyping in nonsevere hemophilia A.}},
author = {{Eckhardt, Corien L. and van Velzen, Alice S. and Peters, Marjolein and Astermark, Jan and Brons, Paul P. and Castaman, Giancarlo and Cnossen, Marjon H. and Dors, Natasja and Escuriola-Ettingshausen, Carmen and Hamulyak, Karly and Hart, Daniel P. and Hay, Charles R. M. and Haya, Saturnino and van Heerde, Waander L. and Hermans, Cedric and Holmstrom, Margareta and Jimenez-Yuste, Victor and Keenan, Russell D. and Klamroth, Robert and Laros-van Gorkom, Britta A. P. and Leebeek, Frank W. G. and Liesner, Ri and Makipernaa, Anne and Male, Christoph and Mauser-Bunschoten, Evelien and Mazzucconi, Maria G. and Mcrae, Simon and Meijer, Karina and Mitchell, Michael and Morfini, Massimo and Nijziel, Marten and Oldenburg, Johannes and Peerlinck, Kathelijne and Petrini, Pia and Platokouki, Helena and Reitter-Pfoertner, Sylvia E. and Santagostino, Elena and Schinco, Piercarla and Smiers, Frans J. and Siegmund, Berthold and Tagliaferri, Annarita and Yee, Thynn T. and Kamphuisen, Pieter Willem and van der Bom, Johanna G. and Fijnvandraat, Karin}},
issn = {{1528-0020}},
language = {{eng}},
number = {{11}},
pages = {{1954--1962}},
publisher = {{American Society of Hematology}},
series = {{Blood}},
title = {{Factor VIII gene (F8) mutation and risk of inhibitor development in nonsevere hemophilia A}},
url = {{http://dx.doi.org/10.1182/blood-2013-02-483263}},
doi = {{10.1182/blood-2013-02-483263}},
volume = {{122}},
year = {{2013}},
}