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 inhibit
Brown, J.E.; Carton, C.L.; Hougie, C.
Journal of Laboratory and Clinical Medicine 97(1): 65-71
1981
ISSN/ISBN: 0022-2143 PMID: 6778942 Document Number: 180065
An IRMA for VIII:CAg was performed on plasma samples from 13 hemophilic and four 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 VII: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 hr incubation at 37 degrees C differed from the residual VIII:CAg in half (three of six) of the high-titer inhibitors (> 30 BIU) 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 to 500 BIU as the VIII:CAg level dropped from 84% to 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+ hemophilia.