[Acquired inhibitors (autoantibodies) to coagulation factors in non-hemophilic patients]

We reported two cases with severe bleeding tendency. Coagulation tests revealed the development of high titer inhibitors to coagulation factor VIII. As results of immunological analyses, the inhibitor from case 1 was found to be IgG type autoantibody having both kappa and lambda light chains. The subclasses were IgG1 and IgG4. The inhibitor from case 1 recognized the COOH-terminal light chain (72kDa thrombin fragment) on the factor VIII molecule as an epitope. On the other hand, the inhibitor from case 2 recognized both epitopes of heavy chain (44kDa thrombin fragment) and light chain (72kDa thrombin fragment). The characteristics of the inhibitors demonstrated no difference between autoantibody and alloantibody from hemophilics as mentioned by Fulcher. These fragments (A2 and C2 domain) may be important on the function of factor VIII. On further progress of epitope analysis of inhibitors, it may be useful to know the structure-function relationship of factor VIII, and applicable to treat the inhibitor patients with some way such as extracorporeal adsorption using a peptide affinity column or peptide-induced neutralization.