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Inhibitors to Factor VIII

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

Authoring team

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

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