[Factor VIII inhibitors in patients suffering from severe haemophilia A: problems of "very low" responders]

Without recognition of any inhibitor until now, low concentrations of factor VIII inhibitors (< 1 Bethesda unit (BU)/mL plasma) can be occasionally measured in patients with severe haemophilia A. The existence of so-called "very low" responders is assessed contradictorily due to a methodically caused inhibitor increase. Plasma from 10 patients with severe haemophilia A was incubated with human plasma or animal plasma from pig, cattle, or cat and assayed for factor VIII inhibitors. No signs of inactivation could be detected in five specimen (0 BU/mL plasma). However, measurable signs of factor VIII inactivation (< 1 BU/mL plasma) did occur in the other five. Therefore, the existence of yet not defined unknown inhibitory substances in certain haemophilic plasmas must be assumed. They are directed against human factor VIII as well as partly against animal factor VIII. These "very low" inhibitors are not identical with factor VIII antibodies of "low" and "high" responding haemophiliacs. The clinical importance of "very low" inhibitors is insignificant because they do not tend to increase after exposure to factor VIII. In fact, a effect of factor VIII therapy is the neutralization of this kind of inhibitors.