Inhibitors in the Swedish population with severe haemophilia A and B: a 20‐year survey

Aim : To survey the entire population ( n = 116) afflicted with severe haemophilia A or B born in Sweden over a 20‐y period (1980–1999), and to examine the epidemiological, genetic and clinical aspects of development of inhibitors to factors VIII and IX (FVIII/FIX). Methods : One hundred of the subjects had haemophilia A and 16 had haemophilia B. All of these subjects had received prophylactic treatment and had a check‐up of inhibitor status at least twice a year. Sixty‐one were born between 1980 and 1989 and 55 between 1990 and 1999. Results : Nineteen percent (19/100) of those with haemophilia A and 37% (6/16) with haemophilia B developed inhibitors at 12–18 mo of age, after exposure to FVIII/FIX concentrates for an average of 14 d in the case of haemophilia A and 16 d in haemophilia B. All patients with inhibitors carried mutations that impaired protein synthesis. The high incidence of FIX inhibitors may have been due to the large number of complete deletions (13%) in the Swedish haemophilia B population. Patients with haemophilia A showed no significant increase ( p = 0.65) in incidence of inhibitors ( n = 10/48, total incidence 21%) in the 1990s, when they were treated mainly with recombinant products, as compared to the 1980s ( n = 9/52,17%), when they received intermediate/high‐purity plasma‐derived concentrates. Conclusion : Our population‐based study verifies that genotype has a general impact on the incidence of FVIII/FIX inhibitors, and that recombinant FIII/FIX concentrates are not a predisposing factor for inhibitor development.