VARIATION IN FACTOR-VIII INHIBITOR REACTIVITY WITH DIFFERENT COMMERCIAL FACTOR-VIII PREPARATIONS

During treatment of a haemophilia A patient with a high-responding inh ibitor against factor VIII coagulant activity (VIII:C), we observed a difference in recovery of VIII:C depending upon which factor concentra te was infused. Inhibitor plasma samples or IgG fraction from seven pa tients were tested against a panel of seven different commercially ava ilable factor VIII concentrates of which five were plasma-derived and two recombinant. In two of the plasma samples, inhibitor titres manife sted a wide range of values depending upon which concentrate was used in the test system. Thus, inhibitor neutralization was less and VIII:C recovery greater when factor VIII concentrates containing large amoun ts of von Willebrand factor were used than when highly purified concen trates containing no von Willebrand factor or only trace amounts were used. In both of these two patients the inhibitor was directed against the light chain of factor VIII, and it is possible that the epitope o f the light chain with which the inhibitor reacts is partly blocked by the von Willebrand factor. We conclude that inhibitors may differ in their reactivity with factor VIII molecules contained in clotting fact or concentrates, and that there is factor VIII epitope variation betwe en different concentrates. These findings have implications for the se lection of concentrates for the treatment of inhibitor patients and th e haemostatic effect may be improved if a concentrate giving the lowes t inhibitor titre is chosen. Thus, in vitro testing of inhibitor react ivity with a panel of concentrates is recommended when treatment of in hibitor patients with factor VIII concentrates is considered.