THE EFFECT OF NATURALLY-OCCURRING ANTIBODIES TO FACTOR-VIII ON AN IMMUNORADIOMETRIC ASSAY FOR FACTOR-VIII COAGULANT ANTIGEN - OBSERVATION ON A CROSS-REACTING MATERIAL-POSITIVE (CRM+) HEMOPHILIAC WITH A FACTOR-VIII INHIBITOR

  • 1 January 1981
    • journal article
    • research article
    • Vol. 97  (1) , 65-71
Abstract
An IRMA [immunoradiometric assay] for VIII:CAg [factor VIII:coagulant antigen] was performed on plasma samples from 13 hemophilic and 4 nonhemophilic subjects, containing naturally occurring antibodies against factor VIII. The VIII:C binding ligand was an iodinated Fab fraction of a high-titer factor VIII antibody arising in a hemophiliac. Since the IRMA is an equilibrium binding assay, the inclusion of an antibody against VIII:C in the test system would be expected to compete with the ligand for the available antigenic sites on the VIII:C molecule: the higher the titer of the antibody expressed in BIU, the greater the degree of inhibition of the IRMA measuring VIII:CAg. In a mixture of equal parts of normal and inhibitor plasmas, the amount of residual VIII:C remaining after 2 h incubation at 37.degree. C differed from the residual VIII:CAg in half (3 of 6) of the high-titer inhibitors (> 30 BIU [Bethesda inhibitor units]) so studied. In the inhibitors of lower titer (< 20 BIU), correlation between BIU and the percentage of VIII:CAg neutralized was not observed. Three of these inhibitor plasmas did not significantly compete with the ligand. With this competitive protein-binding technique, the four plasmas with spontaneous inhibitors could not be distinguished from those arising in hemophiliacs. In one hemophilic plasma, the titer of VIII:C inhibitor over a 6 day span increased from 4-500 BIU as the VIII:CAg level dropped from 84-2%. The finding of circulating VIII:CAg in the presence of an VIII:C inhibitor further substantiates the heterogeneity of the naturally occurring VIII:C antibody and is evidence that factor VIII inhibitors can occur in CRM+ [cross-reacting material positive] hemophilia.

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