Human antibodies that inactivate factor VIII procoagulant activity (VIII:C) are heterogeneous in their kinetic properties. We report there here the properties of four type I and four type II antibodies classified according to Biggs et al. Type I antibodies have second- 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 a significant inhibitor titer. It has been suggested that the antibody- antigen complex in these patients retains some VIII:C activity. This is unlikely, however, 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 the factor-VIII-related protein (VIIIR, von Willebrand factor), appears to be a more important factor, since three of four type II antibodies had inactivating properties like type I antibodies when they were tested with separated VIII:C instead of plasma. Although the fourth type II antibody did not completely inactivate separated VIII:C the residual coagulant activity was adsorbed from this mixture by PAS. These data indicate that type II anti-VIII:C react with different antigenic determinants than type I antibodies and that these determinants are partially blocked in the factor VIII complex by VIIIR.
ARTICLES| November 1, 1982
Inactivation of factor VIII coagulant activity by two different types of human antibodies
Blood (1982) 60 (5): 1103-1109.
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MS Gawryl, LW Hoyer; Inactivation of factor VIII coagulant activity by two different types of human antibodies. Blood 1982; 60 (5): 1103–1109. doi: https://doi.org/10.1182/blood.V60.5.1103.bloodjournal6051103
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