INACTIVATION OF FACTOR-VIII COAGULANT ACTIVITY BY 2 DIFFERENT TYPES OF HUMAN-ANTIBODIES

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  • 1 January 1982
    • journal article
    • research article
    • Vol. 60  (5) , 1103-1109
Abstract
Antibodies to factor VIII develop in .apprx. 5%-20% of patients with severe classic hemophilia who require repeated transfusions. Human antibodies that inactivate factor VIII procoagulant activity (VIII:C) are heterogeneous in their kinetic properties. The properties of 4 type I and 4 type II antibodies classified according to Biggs, et al. are reported. Type I antibodies have 2nd-order inactivation kinetics and completely destroy VIII:C when present in high concentration; type II antibodies have more complex kinetics and do not completely inactivate VIII:C even when tested undiluted. The latter properties correspond to the in vivo finding in some patients that there is detectable VIII:C, even though there is also significant inhibitor titer. It was suggested that the antibody-antigen complex in these patients retains some VIII:C activity. This is unlikely since protein-A-Sepharose (PAS) did not adsorb any VIII:C activity from mixtures of type II antibodies with normal human plasma. An alternate possibility, reduced VIII:C inactivation due to a steric effect of the factor VIII-related protein (VIIR, von Willebrand factor), appears to be a more important factor, since 3 of 4 type II antibodies had inactivating properties like type I antibodies when they were tested with separated VIII:C instead of plasma. Although the 4th type II antibody did not completely inactivate separated VIII:C, the residual coagulant activity was adsorbed from this mixture by PAS. Apparently, type II anti-VIII:C reacts with different antigenic determinants than do type I antibodies, and these determinants are partially blocked in the factor VIII complex by VIIIR.