Inhibitors in congenital haemophilia

Abstract

Inhibitor formation is a serious complication, occurring in 24-52% of patients with haemophilia A and in 1.5-3% of patients with haemophilia B. Low-titre inhibitors can easily be overcome and do not represent a treatment challenge. They are treated with increased doses of factor concentrate. However, high-titre inhibitors may still cause death from haemorrhage in this population. Optimal treatment of acute, life-threatening haemorrhage in patients with factor VIII inhibitors includes either porcine factor VIII or human factor VIII in high doses since, with both modalities, circulating factor levels are achievable. If the inhibitor titres are too high, plasmapheresis may be warranted. For routine joint bleeds, PCC or aPCC can be administered at home with variable success. For patients with factor IX inhibitors treatment options are more limited. If the haemorrhage is life-threatening, plasmapheresis should be done to decrease the inhibitor and high doses of pure factor IX administered either by continuous infusion or bolus. Attainment of levels of > 20% should be attempted. New clinical options, such as rFVIIa, may emerge. For both groups of patients, IT should be started as soon as the inhibitor is discovered and its behaviour characterized. Unfortunately, no standard regimen for IT exists and the treater will have to choose whichever schedule he/she feels is the most appropriate.