Abstract
Hemophilia A (HA) and hemophilia B (HB) are rare congenital severe bleeding disorders,
that may be controlled by proper administration of adequate prophylaxis with factor
VIII (FVIII), and factor IX (FIX) concentrates, respectively, to prevent joint damage
due to recurrent bleeding. However, approximately 30% of patients develop inhibitory
antibodies that render factor replacement therapy ineffective. Due to the high variability
of patients' bleeding tendency, there is a need to “individually tailor treatment”
for this unique group of patients. While replacement therapy with FVIII or FIX can
be used for treating HA or HB patients with low responding inhibitors, hemophilia
patients with high-responding inhibitors are treated with bypassing agents. Unfortunately,
the Bethesda assay applied for inhibitor measurement in most laboratories does not
fully predict either bleeding tendency or therapy response. Immune tolerance induction
(ITI) may eradicate most inhibitors, yet treatment is challenging during bleeding
episodes. The role of bypassing agents and their various treatment strategies still
deserves attention. Recently, new nonreplacement therapies have emerged for patients
with hemophilia including patients with inhibitors. Adequate monitoring of bypassing
therapy and of the new nonreplacement therapies in inhibitor patients is extremely
challenging, thus global hemostatic assays are increasingly used to assess clot formation.
This review aims to summarize the current treatment and monitoring challenges for
inhibitor patients; in this perspective, we will discuss our institutional approach
for optimal decision-making and individual therapy tailoring.
Keywords
hemophilia - inhibitors - bypassing agents - immune tolerance - nonreplacement therapy
