Abstract
A reduction in bleeding pattern and arthropathy appears to be observed in approximately
10% of the patients with severe hemophilia (< 1% clotting factor activity). These
patients rarely bleed and do not always need prophylactic therapy of therapeutic products,
resulting in the wide range of joint damage seen in patients with severe hemophilia.
The cause(s) of this phenotypic heterogeneity has been investigated in many studies
till date, but remains to be completely solved. The large heterogeneity of the clinical
phenotype in severe hemophilia seems to be multifactorial, including variation in
the levels of various procoagulant and anticoagulant factors, the balance between
the coagulation and fibrinolysis systems, pharmacokinetics of therapeutic products,
environmental factors including lifestyle activity, and the limitation of measurement
at lower levels of clotting factors. As an approach toward clarification, studies
should be designed to evaluate a homogenous cohort of hemophilic A patients with an
intron 22 inversion who produce no factor VIII. In the future, by a combination of
the measurement of lower levels of clotting factors and the evaluation of global clotting
function, it might be possible to better grasp the potential of hemostatic coagulation
in individual hemophilia patients, which should in turn be useful for the prediction
of bleeding phenotype and the designation of adequate and long-term hemostatic management
throughout their life.
Keywords
clinical phenotype - severe hemophilia - heterogeneity
