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A circulating plasma inhibitor of the "von Willebrand factor" was observed in a multiply tranfused subject with severe von Willebrand's disease. The platelet-active von Willebrand factor is associated with a plasma protein macromolecular complex that is deficient in the disease. The inhibitor appears to be an IgG antibody, kappa type, based on neutralization tests with goat antisera to specific human immunoglobulins. The IgG and inhibitor separated out together in plasma fractions obtained by "salting-out" and chromatographic procedures. Two separate inhibitor neutralization tests for the platelet-active factor, one with human plasma and ristocetin, the other with bovine plasma, gave similar results, based on the macroscopic aggregation time test of fixed human platelets. With cryoprecipitate transfusions the inhibitor was transiently neutralized with the temporary appearance of von Willebrand factor, factor VIII, and factor VIII-like antigen in the plasma. The plasma inhibitor level increased after transfusion, suggesting an anamnestic response. Lower titer inhibitor plasmas neutralized only the platelet activity. Highest titer plasma also neutralized human factor VIII, but only in part; it did not neutralize either bovine factor VIII or the human small active factor VIII fragment. The anti-factor VIII activity of the von Willebrand factor inhibitor may be due to steric hindrance, dependent on the spatial relationship of factor VIII sites on the macromolecular complex.

Antibody nature of circulating inhibitor of plasma von Willebrand factor.