Abstract
Hemophilia A (HA) and B (HB) are X-linked bleeding disorders caused by mutations in
the F8 or F9 gene that result in the absence, or reduced activity, of the corresponding
clotting factor. The severity of bleeding and related complications is proportional
to the amount of residual circulating functional factor. The development of a safe
and effective hemophilia treatment lasted several decades and has been mainly based
on clotting factor replacement. Advances in the engineering and manufacturing of clotting
concentrates have led to the widespread availability of extended half-life products
that reduced the number of intravenous infusions needed to achieve adequate trough
levels. The recent development of new nonfactor replacement treatments and biotechnology
techniques has offered therapeutic alternatives for hemophilia patients with and without
inhibitors. These are characterized by an easier route of administration, low immunogenicity,
and, regarding gene therapy and cell-based treatments, potential long-term protection
from bleeding after a single treatment course. In this review, we analyze recent progresses
in the management of hemophilia and discuss opportunities and challenges.
Keywords
hemophilia A/B - gene therapy - factor VIII - factor IX
