Variation in factor VIII inhibitor reactivity with different commercial factor VIII preparations: is it of clinical importance?

Abstract

Factor VIII inhibitors may interfere with several important functional binding sites on the factor VIII molecule including that of von Willebrand factor, which binds to the C2 domain. There are in vitro and in vivo observations that inhibitors reacting against the factor VIII light-chain C2 domain may display a lower inhibitor titer against von Willebrand factor containing concentrates as compared to pure products. In low titer inhibitor patients it can be anticipated that von Willebrand factor containing concentrates give a better hemostatic effect. The role in immune tolerance induction is of great interest as an increased success rate and decreased treatment time may have a substantial impact on the cost of treatment. Case reports and treatment experience from some centers indicate a better success rate with von Willebrand factor containing concentrates. Even if formal, well-controlled studies are needed, it can already be recommended that inhibitor plasma should be tested against a panel of concentrates in order to select the less neutralized concentrate for use in inhibitor patients.