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


CONCLUSIONS
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.
Knobe
K E
KE
Department of Paediatrics, University Hospital, Malmö, Sweden. karin.knobe@pediatrik.mas.lu.se
Sjörin
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Tengborn
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Petrini
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Ljung
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D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005164:Factor IX / Q000032:analysis* / Q000037:antagonists & inhibitors* / Q000235:genetics; D005169:Factor VIII / Q000032:analysis* / Q000037:antagonists & inhibitors* / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006306:Health Surveys; D006467:Hemophilia A / Q000097:blood* / Q000453:epidemiology* / Q000235:genetics; D002836:Hemophilia B / Q000097:blood* / Q000453:epidemiology* / Q000235:genetics; D006801:Humans; D015994:Incidence; D007223:Infant; D012720:Severity of Illness Index; D013548:Sweden / Q000453:epidemiology; D013997:Time Factors
D005169:Factor VIII; D005164:Factor IX