TY - JOUR
T1 - Factor VIII gene (F8) mutation and risk of inhibitor development in nonsevere hemophilia A
AU - Eckhardt, Corien L.
AU - van Velzen, Alice S.
AU - Peters, Marjolein
AU - Astermark, Jan
AU - Brons, Paul P.
AU - Castaman, Giancarlo
AU - Cnossen, Marjon H.
AU - Dors, Natasja
AU - Escuriola-Ettingshausen, Carmen
AU - Hamulyak, Karly
AU - Hart, Daniel P.
AU - Hay, Charles R. M.
AU - Haya, Saturnino
AU - van Heerde, Waander L.
AU - Hermans, Cedric
AU - Holmström, Margareta
AU - Jimenez-Yuste, Victor
AU - Keenan, Russell D.
AU - Klamroth, Robert
AU - Laros-van Gorkom, Britta A. P.
AU - Leebeek, Frank W. G.
AU - Liesner, Ri
AU - Mäkipernaa, Anne
AU - Male, Christoph
AU - Mauser-Bunschoten, Evelien
AU - Mazzucconi, Maria G.
AU - McRae, Simon
AU - Meijer, Karina
AU - Mitchell, Michael
AU - Morfini, Massimo
AU - Nijziel, Marten
AU - Oldenburg, Johannes
AU - Peerlinck, Kathelijne
AU - Petrini, Pia
AU - Platokouki, Helena
AU - Reitter-Pfoertner, Sylvia E.
AU - Santagostino, Elena
AU - Schinco, Piercarla
AU - Smiers, Frans J.
AU - Siegmund, Berthold
AU - Tagliaferri, Annarita
AU - Yee, Thynn T.
AU - Kamphuisen, Pieter Willem
AU - van der Bom, Johanna G.
AU - Fijnvandraat, Karin
PY - 2013
Y1 - 2013
N2 - 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
AB - 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
U2 - https://doi.org/10.1182/blood-2013-02-483263
DO - https://doi.org/10.1182/blood-2013-02-483263
M3 - Article
C2 - 23926300
SN - 0006-4971
VL - 122
SP - 1954
EP - 1962
JO - Blood
JF - Blood
IS - 11
ER -