Prophylaxis with Recombinant Activated Factor VII in Hemophilia Patients with Inhibitors

Review Article

Prophylaxis with Recombinant Activated Factor VII in Hemophilia Patients with Inhibitors

Günter Auerswald ¹ and Massimo Morfini ²
Affiliations: ¹Prof.-Hess-Kinderklinik, Bremen, Germany and ²Agency for Hemophilia, Azienda Ospedaliero Universitaria Careggi, Florence, Italy


ABSTRACT

Treatment of bleeding episodes or during surgery in people with hemophilia A (FVIII deficiency) or hemophilia B (FIX deficiency) who have developed antibodies (inhibitors) to FVIII or FIX (especially high titer inhibitors) is difficult as a normal replacement with factor VIII or IX is not effective. rFVIIa is used to treat bleeds in patients with hemophilia who have developed such antibodies to FVIII or FIX (inhibitors, especially high titer inhibitors). Its effects on the coagulation system, however, may last for longer than pharmacokinetic data suggest. Furthermore, data supporting the concept of rFVIIa‐mediated prophylaxis in hemophilia patients with inhibitors are now being published. A recently described clinical trial of prophylaxis with rFVIIa in 22 frequently bleeding hemophilia patients with inhibitors was the first to report the results of a prospective randomized study evaluating the potential benefits of a bypassing agent in such a prophylactic setting. Here we review data from this study together with other information currently available relating to the prophylactic use of rFVIIa in patients with hemophilia and inhibitors outside the surgical arena. Overall, data from more than 70 patients described in a range of publications suggest that prophylaxis with rFVIIa can decrease bleeding frequency, increase mobility, reduce pain and have other quality of life benefits in hemophilia patients with inhibitors. There are no reports of any adverse event profiles attributable to the use of rFVIIa in these patients. The prolonged prophylactic effect of rFVIIa may be explained, at least in part, by its diffusion into the extravascular space and the formation of complexes with tissue factor to facilitate thrombin generation on platelets. In addition, rFVIIa could be internalized into platelets, which subsequently increases the duration of its availability. Further research into rFVIIa prophylaxis and its mechanism of action in hemophilia patients with inhibitors is warranted.

Keywords: Hemophilia, inhibitors, prophylaxis, recombinant activated factor VII
Correspondence: Günter Auerswald , MD, Prof.‐Hess‐Kinderklinik, Klinikum Bremen‐Mitte, St.‐Jürgen‐Straße 1, D28177 Bremen, Germany, Tel: (+49‐421)4975410, Fax: (+49‐421)4973311, e‐mail: guenterauerswald@aol.com