Abstract
The original aim of prophylactic replacement therapy was to convert the bleeding pattern
of severe hemophilia to that of moderate hemophilia through regular infusions of clotting
factor concentrates. However, targeting prophylaxis on minimum trough levels does
not prevent all bleeding. At the group level, there is a clear association of factor
levels with bleeding and outcome. But bleeding phenotype in individual patients shows
large variation, independent of trough levels maintained. The association of peak
levels with bleeding on prophylaxis is not established. Experience with surgery suggests
that certain peak levels need to be achieved during other hemostatic challenges, such
as playing sports. Individualization of prophylaxis should include timing of infusion
according to special activities. The clinical relevance of factor levels is even more
urgent since the recent introduction of long-acting clotting factor concentrates with
their different pharmacokinetic profiles and the prospect of gene therapy resulting
in constant factor levels. It should be considered that the success of any prophylactic
regimen is also dependent on other factors, such as the age at initiation of prophylaxis,
adherence, lifestyle, cartilage susceptibility, and the other components of the clotting
system. Factor levels are thus an important but quite small piece in the total picture
of treating hemophilia and we currently cannot identify a specific trough or peak
level to use for monitoring. At the same time, knowledge of a patients' level during
the infusion intervals may help to individualize and adjust treatment according to
the clinical symptoms.
Keywords
prophylaxis - pharmacokinetics - trough level - peak level
