Approximately 10% of treated haemophiliacs develop anti-Factor VIII antibodies. Such inhibitors also may arise spontaneously in previously normal individuals - particularly those with autoimmune disease, lymphoreticular malignancy, pregnancy, penicillin allergy and the elderly.
Their onset is usually noticed by the patient who reports a change in the usual response to Factor VIII replacement. Laboratory tests confirm suboptimal recovery and survival of infused Factor VIII. There may be a family propensity.
Management of this complication includes:
- bi-annual screening of all treated patients for signs of inhibitor development
- reduce / stop Factor VIII replacement therapy - use more conservative measures - bedrest, splinting, cold compresses
- increase dose and frequency of Factor VIII concentrate
- use heterologous Factor VIII - purified porcine Factor VIII now has fewer toxic side-effects than in the past
- use prothrombin complex concentrates - of the vitamin K dependent clotting factors - II (prothrombin), VII, IX (Christmas Factor) and X - but activity is still less effective than non-inhibitor haemophiliacs treated with Factor VIII
- immunosuppression - beneficial in non-haemophiliacs who spontaneously develop anti-Factor VIII antibodies, but not in inhibitor-haemophiliacs because of long term consequences
- immunodepletion - by intensive plasma exchange or extracorporeal perfusion of immunoglobulin G binding proteins - eg. staphylococcal protein A - effective because the inhibitors are themselves immunoglobulins