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- Title
Different factor VIII neutralizing effects on anti-factor VIII inhibitor antibodies associated with epitope specificity and von Willebrand factor.
- Authors
Yada, Koji; Nogami, Keiji; Shima, Midori
- Abstract
Inhibitor neutralization therapy based on factor ( F) VIII replacement is used for haemostatic treatment in haemophilia A patients with inhibitors on low responder, but effects appear to depend on various properties of inhibitors. We investigated this nature by evaluating the global coagulation function in timed-reactions after mixing FVIII (1 U/ml) with anti- FVIII alloantibodies containing distinct epitopes (2·5 Bethesda units/ml). Thrombin generation assays showed that peak thrombin and mean velocity to peak thrombin were depressed by anti- C2 type 1 inhibitors to significantly greater extents than by anti- A2 type 1 and anti- C2 type 2 (2- to 6-fold and 10- to 20-fold, respectively). In the presence of FVIII-von Willebrand Factor ( VWF) complex, the anti- C2 type 1-mediated decreased thrombin generation was reduced by 20-40%, reflecting the protective function of VWF. However, the activities of anti- A2 type 1 were little affected, and that of anti- C2 type 2 was rather enhanced by c. 2·5-fold, relative to FVIII. Clot waveform analysis also showed similar patterns. Anti- FVIII monoclonal antibodies with well-defined characteristics demonstrated similar reactions to those with polyclonal inhibitors. In conclusion, the neutralizing effects of FVIII(- VWF) depending on epitopes could have significant therapeutic implications, and it could be important to determine inhibitor properties in order to predict the effects of infused FVIII in neutralization therapy.
- Subjects
BLOOD coagulation factor VIII; HEMOPHILIACS; BLOOD coagulation; BLOOD coagulation factor VIII antibodies; EPITOPES; THROMBIN; VON Willebrand factor
- Publication
British Journal of Haematology, 2013, Vol 163, Issue 1, p104
- ISSN
0007-1048
- Publication type
Article
- DOI
10.1111/bjh.12473