Abstract
A circulating anticoagulant, which specifically inhibits Factor VIII (AHF), has been detected in some patients with hemophilia A who had received multiple transfusions. The inhibitor was quantitated by measurement of the degree of inactivation of Factor VIII. The data presented provide strong evidence for the antibody nature of the Factor VIII inhibitor in hemophilia: (1) All specific inhibitory activity of serum was detected in the γG globulin obtained by chromatography of the sera on DEAE cellulose. (2) Fab fragments obtained by digestion of the γG globulin with papain, contained 18-22 per cent of the specific inhibitory activity, while Fc fragments contained 0.4-3 per cent. F(ab')2 fragments obtained by digestion with pepsin contained 36-61 per cent of the specific inhibitory activity of γG globulin. (3) The level of the inhibitor of Factor VIII increased sharply following transfusions of blood and decreased slowly to its preinfusion level. (4) When small amounts of inhibitor were incubated in vitro with excess Factor VIII, the inhibitor activity was decreased. Infusion of Factor VIII into a patient with a low level of inhibitor decreased the inhibitor activity. (5) Clearance of the isologous inhibitor from the circulation of a normal subject was rapid.

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