The literature on inhibitors: Articles that influence my management of patients with hemophilia A and high‐titer inhibitors

Abstract

High‐titer inhibitors represent the greatest management challenge faced by clinicians who treat patients with hemophilia A, as bleeding episodes no longer respond to standard factor VIII replacement therapy. Over the last seven decades, major strides have been made in inhibitor treatment. This article focuses on the seminal clinical observations and studies that provided the foundation for these advances in hemophilia care. Am. J. Hematol. 2012. © 2012 Wiley Periodicals, Inc.

Outcome measures for adult and pediatric hemophilia patients with inhibitors

“…Developments for patients who are refractory to standard replacement therapy due to the development of alloantibodies (inhibitors) against infused FVIII or FIX have followed more slowly. For many years, the only specific therapy for treating acute bleeds in these inhibitor patients was plasma‐derived activated prothrombin complex concentrate (pd‐aPCC [FVIII inhibitor bypassing activity]) . However, within the last four decades, this otherwise limited therapeutic armamentarium for inhibitor patients has also been expanded: first, by the introduction of immune tolerance induction (ITI), which offers the possibility of inhibitor eradication, and then by the development of recombinant activated factor VII, the first recombinant bypassing agent for the treatment of acute bleeding episodes in inhibitor patients .…”

“…For many years, the only specific therapy for treating acute bleeds in these inhibitor patients was plasma-derived activated prothrombin complex concentrate (pd-aPCC [FVIII inhibitor bypassing activity]). 5,6 However, within the last four decades, this otherwise limited therapeutic armamentarium for inhibitor patients has also been expanded: first, by the introduction of immune tolerance induction (ITI), 7 which offers the possibility of inhibitor eradication, and then by the development of recombinant activated factor VII, the first recombinant bypassing agent for the treatment of acute bleeding episodes in inhibitor patients. 2,3,8 Furthermore, ongoing bioengineering efforts to develop novel coagulation factors with improved properties are heralding another new phase of hemophilia management, 2,4 with new products now starting to emerge onto the market.…”