Binding to phospholipid protects factor VIII from inactivation by human antibodies

The addition of purified factor IXa and phospholipid to factor VIII concentrate protected the VIII:C from inactivation by human antibodies. This protective effect was shown to be due largely to the phospholipid. Addition of phospholipid alone gave substantial protection against even high-titer antibodies, as shown by measurements of thrombin generation and VIII:C assays. Increasing concentrations of phospholipid led to significant reductions in the amount of VIII C:Ag detected by an IRMA method, up to 70% of the original VIII C:Ag being "lost" at the highest concentration of phospholipid. These results indicate that phospholipid binding plays an important part in the procoagulant activity of factor VIII and that human antibodies to VIII:C are directed largely at the phospholipid binding site. The addition of phospholipid to factor VIII concentrates could have important clinical applications in the treatment of hemophiliacs with antibodies to factor VIII.