High-dosed intensive factor VIII treatment increases the risk of inhibitor development in severe hemophilia A patients
In severe hemophilia A patients factor VIII prophylaxis decreases the inhibitor risk, especially in patients with low-risk F8 mutations.
The study objective was to examine the association of the intensity of treatment, ranging from high-dosed intensive factor VIII (FVIII) treatment to prophylactic treatment, with the inhibitor incidence among previously untreated patients with severe hemophilia A. This cohort study aimed to include consecutive patients with a FVIII activity <0.01 IU/mL born between 2000-2010, followed during their first 75 FVIII exposure days. Intensive FVIII treatment for hemorrhages or surgery at start of treatment was associated with an increased inhibitor risk (adjusted hazard ratio (aHR) 2.0; 95% confidence interval [CI] 1.3-3.0). High-dosed FVIII treatment was associated with a higher inhibitor risk than low-dosed FVIII treatment (aHR 2.3 (CI 1.0-4.8). Prophylaxis was only associated with a decreased overall inhibitor incidence after 20 exposure days to FVIII. The association with prophylaxis was more pronounced in patients with low-risk F8 genotypes than in patients with high-risk F8 genotypes (aHR 0.61, CI 0.19-2.0 and 0.85, CI 0.51-1.4, respectively). In conclusion, our findings suggest that in previously untreated patients with severe hemophilia A, high-dosed intensive FVIII treatment increases the inhibitor risk and prophylactic FVIII treatment decreases the inhibitor risk, especially in patients with low-risk F8 mutations.
- Submitted September 20, 2012.
- Accepted March 12, 2013.
- Copyright © 2005 American Society of Hematology