Inhibitors in young boys with haemophilia

Abstract

The development of an inhibitor antibody to factor VIII (or factor IX) in a child with haemophilia presents a major challenge to the paediatric haematologist. This article provides an overview of the incidence of inhibitor development in early childhood (30–52% in boys with severe haemophilia A), genetic risk factors, detection, high titre, low titre and transient inhibitors, and management. Treatment of patients with inhibitors is time-consuming and expensive. One should make every attempt to ensure that the boy's family has an understanding of inhibitors, treatment options, and just what is being recommended for their child and what this involves. Immune tolerance induction is successful in ∼85% of boys with factor VIII inhibitors, but in only 40–50% of those with factor IX inhibitors. For treatment of bleeding episodes in children with high-titre (⩾5 Bethesda Units) inhibitors, therapeutic options include activated prothrombin complex concentrates (APCC), rF VIIa, and (for factor VIII inhibitors) porcine factor VIII. The advantages and disadvantages of each are discussed. Although factor IX inhibitors are far less common (occurring in 2–3% of boys with haemophilia B), approximately 50% are accompanied by the occurrence of anaphylaxis or severe allergic reactions to any factor IX-containing product.