Mild
hemophilia A (HA), defined by clinical features and
factor VIII coagulant activity (FVIII:C) between 0.05 and 0.40 IU mL(-1), is characteristically distinct from severe HA. Indeed, although the molecular characterization of mild HA has permitted the identification of specific underlying mutations, its clinical phenotype is strikingly different from that of patients with a severe FVIII defect, where spontaneous
hemorrhages or recurrent joint
bleeding are usual manifestations. With aging, mild HA patients may develop complications (i.e.
cancers and cardiovascular disorders), the management of which may prove challenging due to the concomitant
bleeding tendency. Furthermore, the development of inhibitors provides an additional major complication in these patients, because it increases the severity of the
bleeding phenotype and complicates their management. Standard management of mild HA includes the use of
desmopressin and
antifibrinolytic agents for minor
bleeding episodes or
surgical procedures, whilst major
bleeding or surgery requires replacement
therapy with FVIII concentrates. As regards treatment of patients with inhibitors, bypassing agents (i.e. activated
prothrombin complex concentrates and recombinant activated FVII) have proven effective in the treatment of
bleeding episodes, but as there are insufficient data to determine the optimal approach to immune tolerance induction in this group of patients, their optimal management remains controversial.
Rituximab is a newer, promising therapeutic option for inhibitor eradication in such patients. Many aspects concerning mild HA remain to be clarified, including the molecular basis, the natural history and the optimal diagnostic and therapeutic strategies. Only large prospective studies will shed light on this condition.