In non-severe hemophilia A the risk of inhibitor after intensive factor treatment is greater in older patients: a case-control study.
BACKGROUND
Twenty-five percent of new anti-factor VIII (FVIII) antibodies (inhibitors) that complicate hemophilia A occur in those with mild and moderate disease. Although intensive FVIII treatment has long been considered a risk factor for inhibitor development in those with non-severe disease, its strength of association and the influence of other factors have remained undefined.


OBJECTIVE
To evaluate risk factors for inhibitor development in patients with non-severe hemophilia A.


METHODS
Information on clinical and demographic variables and FVIII genotype was collected on 36 subjects with mild or moderate hemophilia A and an inhibitor and 62 controls also with mild or moderate hemophilia A but without an inhibitor.


RESULTS
Treatment with FVIII for six or more consecutive days during the prior year was more strongly associated with inhibitor development in those ≥30years of age compared with those <30years of age [adjusted odds ratio (OR) 12.62; 95% confidence interval (CI), 2.76-57.81 vs. OR 2.54; 95% CI, 0.61-10.68]. Having previously received <50days of FVIII was also not statistically associated with inhibitor development on univariate or multivariate analysis.


CONCLUSIONS
These findings suggest that inhibitor development in mild and moderate hemophilia A varies with age, but does not vary significantly with lifetime FVIII exposure days: two features distinct from severe hemophilia A.
Kempton
C L
CL
Aflac Cancer Center and Blood Disorders Service and Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, USA. christine.kempton@emory.edu
Soucie
J M
JM
Miller
C H
CH
Hooper
C
C
Escobar
M A
MA
Cohen
A J
AJ
Key
N S
NS
Thompson
A R
AR
Abshire
T C
TC
D000328:Adult; D000367:Age Factors; D000368:Aged; D016022:Case-Control Studies; D005169:Factor VIII / Q000276:immunology* / Q000627:therapeutic use; D005838:Genotype; D006467:Hemophilia A / Q000097:blood* / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020125:Mutation, Missense; D012307:Risk Factors
D005169:Factor VIII