Antibodies to factor VIII. V. Patterns of immune response to factor VIII in hemophilia A

The natural history of factor VIII antibodies was studied in 20 severe, multitransfused hemophiliacs. Two patterns of humoral immune reactivity were observed. In one group of ten, who developed antibodies after an average of 22 cumulative exposure days to factor VIII, the antibody titers increased after each antigenic stimulation or persisted for years in the absence of transfusion. These patients were designated as high-responding hemophiliacs. In the second group of ten patients, the factor VIII neutralizing activity appeared after a longer exposure period (48 days). Antibody titers remained low, and there was no significant difference in individual titers before and 8--20 days following transfusion. Antibody affinity did not increase after renewed antigenic challenge. This pattern characterized low-responding hemophiliacs. The latter group of patients benefited from repeated placement therapy required by the clinical situation.