Abstract
Hemophilia A/B are caused by deficiency or lack of coagulation factors VIII (FVIII)
or factor IX (FIX), respectively, in plasma. A person with hemophilia develops bleeding
in the joints and muscles at an early age, which, if left untreated, leads to early
arthropathy. Preventive treatment can be achieved by regular (prophylactic) administration
of FVIII/FIX. In 1958, this was implemented on a small scale in Sweden with FVIII
in patients with severe hemophilia A, and in those with hemophilia B in 1972 when
FIX became available. However, there were problems with human immunodeficiency virus
and hepatitis infection from contaminated blood products. In the 1990s, recombinant
FVIII and FIX concentrates were introduced. The major remaining problems then were
the development of inhibitors, and the need for a venous route for the injections
in very young children. High-titer inhibitors were treated by immune tolerance induction
according to a modified model of the original Bonn high-dose protocol. A central venous
line, i.e., Port-A-Cath, has enabled early prophylaxis in many children with poor
venous access and has enabled the early start of home treatment with adequate injection
frequency. Scoring systems for X-rays, magnetic resonance imaging, and function of
joints were developed early in Sweden and have been widely disseminated worldwide,
partly with modifications. Extended half-life products with half-life increased three
to five times have been developed, which can provide superior bleed protection when
dosed once-weekly and can maintain therapeutic trough levels when administered less
frequently. The ultimate prophylaxis therapy in the future may be gene therapy.
Keywords
hemophilia A - hemophilia B - pediatric - prophylaxis - factor VIII - factor IX
