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Inhibitor development

Treatment options following inhibitor development

Patients in whom inhibitory antibodies to factor VIII or IX that arise post-concentrate infusion require specialised treatment, as discussed here

Christopher A Ludlam BSc(Hons) MB ChB PhD FRCP FRCPath Emeritus Professor of Haematology and Coagulation Medicine University of Edinburgh, UK

A patient with haemophilia may develop an inhibitory antibody to factor VIII or IX following treatment with either factor VIII or IX concentrate because his immune system identifies the infused clotting factor as a foreign protein. The antibody neutralises the activity of subsequent infusions of clotting factor, which is rapidly cleared from the circulation, and these do not prevent or stop bleeding. Inhibitors in haemophilia A are relatively common and most of this chapter describes how such patients should be managed. The situation is different in haemophilia B, in which inhibitors are uncommon (<1-2%), and their characteristics and clinical consequences are quite different from those arising in haemophilia A; they will, therefore, be described separately at the end of this chapter. Several excellent recent reviews have been published.1–3

Haemophilia A

An inhibitor is observed in about a quarter of small children with severe haemophilia A, usually between one and two years of age, and occurs after 10–15 treatments with factor VIII concentrate. In those with mild/moderate haemophilia A,

Inhibitor measurement

The concentration of an inhibitor in the blood can be assessed in the laboratory by the Nijmegen-Bethesda assay. This quantifies the ability of the antibody to inhibit factor VIII in a sample of plasma

an inhibitor arises later in life and is most commonly observed after a period of intensive (> five days) treatment for a severe bleed or to cover surgery. The chance of an individual developing an inhibitor depends upon a number of patient characteristics as well as the intensity of treatment (Table 1).

after a two-hour incubation. A low-level inhibitor is <5 Bethesda units (Bu)/ml whereas one >5 Bu/ml is considered to be one of high level. Low-responding inhibitors are those that always remain <5 Bu/ml, whereas high responding ones rise to >5 Bu/ml after further treatment with factor VIII (anamnestic response). A reduction in the half-life of infused factor VIII is the most sensitive indicator of the presence of an inhibitor; a t1/2


less than seven hours is usually interpreted as being indicative of its presence. The t1/2

the absence of an inhibitor is of infused factor VIII in 21

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