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An antibody to Factor VIII in non-hemophiliacs is a rare occurrence. The presence of low but detectable Factor VIII: C (VIII: C) and high Factor VIII antigen (VIIIR: Ag), together with high antibody levels, suggests a complex influence of anti- VIII: C on Factor VIII metabolism.  We have studied Factor VIII complex in 16 non-hemophilic patients with anti-VIII: C. VIII: C, VIIIR: Ag and VIII: Rcof were measured by standard techniques and VIII: C antigen (VIII: CAg) by a liquid phase immunoradiometric assay using radio labelled anti-VIII:C Fab’ fragments purified from a hemophiliac.  The plasma from all patients had low VIII: C (0.01 - 0.24 u/ml) and high VIIIR:Ag (1.4 - 8.8 u/ml) content. VIII:Rcof was approximately 50% of the VIIIR:Ag level. An increase in electrophoretically fast-moving VIIIR: Ag was observed in some cases  VIII: CAg was tested in 13 patients. Two patterns of the dose response were observed. In most samples obtained from patients with low affinity anti-VIII:C whose VIII: CAg ranged from 0.19 - 2.45 u/ml, the dose response paralleled that of the control. In patients with high affinity antibodies the dose response curve was less steep than control, suggesting a competition between the patient’s antibody and the hemophilic anti-VIII: C Fab’ fragments for the VIII: C antigenic sites  The Factor VTII complex was studied sequentially in 3 patients during immunosuppression. The results showed that : 1) when VIII: C normalizes, VIIIR: Ag levels and electrophoretic mobility progressively return to normal ; 2) levels of VIIIR: Ag are inversely correlated to the VIII: C irrespective of VIII: CAg levels ; 3) high VIII: CAg levels correspond to VIII:C-anti-VIII: C circulating immune complexes.  In non-hemophilic patients low VIII: C, high VIII:CAg and high VIIIR: Ag indicate the presence of an anti-VIII: C inhibitor. Measurements of various components of Factor VIII in these patients are not only a means for monitoring the effect of therapy but also provide a rare opportunity to study the metabolism of Factor VIII in man.

Factor VIII Complex In Non-Hemophilic Patients With Antibody To Factor VIII: C