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Thromb Haemost 1999; 81(01): 39-44
DOI: 10.1055/s-0037-1614415
Review Article
Schattauer GmbH

Inhibitors in German Hemophilia A Patients Treated with a Double Virus Inactivated Factor VIII Concentrate Bind to the C2 Domain of FVIII Light Chain

R. Laub
1   From the Red Cross, Brussels, Belgium
,
Di M. Giambattista
1   From the Red Cross, Brussels, Belgium
,
P. Fondu
2   Hôpital Universitaire Brugmann, Brussels
,
H.-H. Brackmann
3   University of Bonn, Germany, Rockville, MD, USA
,
H. Lenk
4   University of Leipzig, Germany, Rockville, MD, USA
,
E. L. Saenko
5   American Red Cross, Rockville, MD, USA
,
M. Felch
5   American Red Cross, Rockville, MD, USA
,
D. Scandella
5   American Red Cross, Rockville, MD, USA
› Author Affiliations
Further Information

Publication History

Received04 May 1998

Accepted after revision15 September 1998

Publication Date:
08 December 2017 (online)

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Summary

To reduce the risk of transmission of hepatitis A virus, an Octaphar-ma produced factor VIII (fVIII) concentrate treated with solvent detergent (FVIII-SD) was further pasteurized after purification. This product, Octavi SDPlus (FVIII-SDP), was marketed in Europe in 1993 to 1995. Inhibitors appeared from September to October, 1995, in 12 of 109 previously treated German hemophilia A patients. A study of similarly treated Belgian patients, who also developed inhibitors, had shown antibodies to the fVIII light chain (domains A3-C1-C2) only. In the present study, the epitope specificity of 8 German inhibitor plasmas was also found to be restricted to the light chain. In radioimmunoprecipitation assays to localize the light chain epitope(s), antibody binding to heavy chain (domains A1-A2-B) was 11-148 fold lower than to the C2 domain, and binding to recombinant A3-C1 was barely detectable. These results were supported by >95% neutralization of a high responder inhibitor titer by the C2 domain.

 

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