Abstract
Nonsevere hemophilia A (NSHA) is an inherited X-linked bleeding disorder, caused by
mutations of the F8 gene, leading to decreases of clotting factor VIII (FVIII) levels to 1 to 40 IU/dL.
Desmopressin is the first therapeutic option for NSHA, but 40 to 50% of patients fail
to attain adequate postinfusion FVIII levels. Thus, in these cases, FVIII concentrates
remain the mainstay of treatment. The development of neutralizing FVIII antibodies
(inhibitors) is a major challenge with replacement therapy. In contrast to severe
disease, NSHA patients have a lifelong risk of inhibitor development. Recent data
indicate that inhibitors are associated with a deterioration of clinical outcome,
illustrated by an increase in bleeding and mortality rate. F8 genotype is an important risk factor for inhibitor occurrence together with surgical
interventions and a high dose of FVIII concentrate. Adequate prevention and treatment
of inhibitors in NSHA patients is limited by a lack of understanding of the underlying
immunological mechanisms. Elucidation of the immunology driving inhibitor development
is required to identify high-risk patients, to understand the association between
clinical risk factors and inhibitor occurrence, and to provide the opportunity to
develop new preventive and therapeutic strategies.
Keywords
nonsevere hemophilia A - diagnosis - treatment - inhibitor development - immunological
characteristics
