Review of the Literature of FEIBA Administration in Patients with Hemophilia B and Inhibitors

Introduction

The development of inhibitors is one of the most challenging adverse consequences of factor replacement therapy in hemophilia. Inhibitor development in hemophilia B is relatively rare, affecting around 2%–4% of individuals1 in contrast to hemophilia A, which is associated with the development of inhibitors in 20%–30% of patients.2 Around half of all inhibitors are detected before the age of 10 years, with studies suggesting a peak in incidence at around 2 years of age.2 The majority of inhibitor patients (~80%) are high responders2 and are associated with major gene deletions.

Abstract

During the last three decades, the use of FEIBA (Factor Eight Inhibitor Bypassing Activity, Baxter AG, Vienna, Austria) has steadily increased in the management of patients with hemophilia A and inhibitors. This literature review focuses on the reported use of FEIBA in hemophilia B patients with inhibitors, as these rare individuals present with unique management challenges. We have identified and described a total of 37 reports (1979–2010) on the use of FEIBA in 46 hemophilia B patients aged 2–70 years with inhibitors. FEIBA effectively and safely controlled a range of acute soft tissue and joint hemorrhages including several severe and life-threatening bleeding episodes. When used to cover surgery, FEIBA provided appropriate hemostatic control, enabling even major surgeries to be completed successfully. FEIBA also provided effective bleed prevention, allowing several individuals to undergo intensive rehabilitation with good long-term clinical outcomes. FEIBA was well tolerated in the majority of cases reported, although anaphylaxis to factor IX (FIX) was reported in six patients. There were no reports of nephrotic syndrome, but three thrombotic complications were potentially related to FEIBA administration. This review demonstrates that over recent years, anti-inhibitor treatment strategies have been extended to hemophilia B patients with inhibitors including prophylaxis, immune tolerance induction (ITI), and surgery. Although accepting the limitations of using a case series approach to evaluate the efficacy and safety of FEIBA in hemophilia B patients with inhibitors, the findings reported suggest that FEIBA represents an essential treatment option for these rare but clinically challenging individuals.

Keywords

FEIBA, hemophilia B, inhibitors, bypassing agents