Inhibitors in German hemophilia A patients treated with a double virus inactivated factor VIII concentrate bind to the C2 domain of FVIII light chain

Citation
R. Laub et al., Inhibitors in German hemophilia A patients treated with a double virus inactivated factor VIII concentrate bind to the C2 domain of FVIII light chain, THROMB HAEM, 81(1), 1999, pp. 39-44
Citations number
27
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
THROMBOSIS AND HAEMOSTASIS
ISSN journal
03406245 → ACNP
Volume
81
Issue
1
Year of publication
1999
Pages
39 - 44
Database
ISI
SICI code
0340-6245(199901)81:1<39:IIGHAP>2.0.ZU;2-8
Abstract
To reduce the risk of transmission of hepatitis A virus, an Octapharma prod uced 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 f rom September to October, 1995, in 12 of 109 previously treated German hemo philia A patients. A study of similarly treated Belgian patients, who also developed inhibitors, had shown antibodies to the fVIII light chain (domain s 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 r adioimmunoprecipitation assays to localize the light chain epitope(s), anti body 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, The se results were supported by >95% neutralization of a high responder inhibi tor titer by the C2 domain.