Vaskulárna medicína 3-4/2017

Hemophilia A and risk of inhibitor development – what changed the SIPPET study?

Inhibitor development is considered to be the most problematic and costly complication of hemophilia treatment. The process of inhibitor development depends on a complex multifactorial immune response that is influenced by patient- and treatment-related factors. Current research is focused on inhibitor development as well as the mechanism of eradication through immune tolerance induction (ITI). Once an inhibitor develops, two general treatment options are available: a) to treat acute bleeds through bypassing agents, and b) to eradicate the inhibitor permanently through ITI. Previously untreated patients (PUP) are at greatest risk of inhibitor development within the first 20 exposure days to factor VIII (FVIII). Inhibitor incidence in PUP studies ranges from 0% to as high as 52%. Plasma-derived FVIII (pdFVIII) concentrates have repeatedly been shown in cohort studies to be associated with a decreased inhibitor risk compared with recombinant FVIII (rFVIII) concentrates, but results from randomized clinical trials were lacking. However, recent multicenter randomized study SIPPET has found the rFVIII product class associated with 1,87-fold higher incidence of inhibitors than the pdFVIII class in PUP with severe hemophilia A. It seems that von Willebrand factor (vWF) has the role in immunoprotection against development of FVIII inhibitor, but this potential effect of vWF is currently under review.

Keywords: inhibitors, hemophilia A, previously untreated patients (PUPs), von Willebrand factor (vWF), inhibitor risk management