Altered serum factor VIII-related antigen (VIII:AGN)/von Willebrand factor (VIII:vWf) in haemophiliacs with inhibitors to factor VIII procoagulant activity (VIII:C)

Inhibitors to factor VIII (anti-F VIII) developing in patients with classic haemophilia have apparent specificity for the factor VIII procoagulant activity (VIII:C), rather than the factor VIII-related antigen (VIII:AGN) and von Willebrand factor (VIII:vWf) regions of the factor VIII complex. Since procoagulant function is absent following in vitro clotting, but serum retains VIII:AGN/vWf properties, we searched for differences in VIII:AGN and VIII:vWf of inhibitor serum that might relate to the presence of anti-F VIII. Rocket immunoelectrophoresis and the washed platelet ristocetin assay were performed on the plasma and serum of 9 haemophiliacs with inhibitors, 23 non-inhibitor haemophiliacs and 6 normal subjects. Unlike normal and non-inhibitor haemophilic sera, that from 5 of 9 inhibitor patients demonstrated absent VIII:vWf and significantly lower VIII:AGN (p <0.05). Furthermore, VIII:AGN of faster mobility was detected on crossed immunoelectrophoresis of the sera of 3 inhibitor patients. Thrombin clotting of plasma from haemophiliacs with high titer anti-F VIII was associated with a greater loss of VIII:vWf than seen with non-inhibitor haemophilic plasma. This effect was independent of the presence of platelets. These data indicate that in vitro clotting is associated with alteration in the serum VIII:AGN/vWf of some haemophiliacs with anti-F VIII.