Plasma from 54 patients with hemophilia A was tested for neutralizing activity with a human antibody to factor VIII. The plasma from 52 patients had no demonstrable neutralizing activity. Two plasma samples had neutralizing activity equivalent to that of normal plasma despite the lack of factor VIII clotting activity. Apparently, most patients with hemophilia A do not synthesize factor VIII, whereas a few synthesize an inactive molecule with a presumed genetic structural mutation of the active site but with antigenic determinants in common with normal factor VIII. Thus, hemophilia A is a disease caused by more than a single genetic mechanism.
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