Safety of recombinant activated factor VII for treatment of breakthrough bleeds in patients with congenital haemophilia A and inhibitors receiving emicizumab prophylaxis: Review of the real‐world evidence

Author:

Kenet Gili1ORCID,Fujii Teruhisa2ORCID

Affiliation:

1. The Israeli National Hemophilia Center and Thrombosis Unit Sheba Medical Center and the Amalia Biron Research Institute of Thrombosis and Hemostasis Tel Aviv University Tel Hashomer Israel

2. Division of Blood Transfusion Hiroshima University Hospital Hiroshima Japan

Abstract

AbstractBackgroundEmicizumab is used as a subcutaneous prophylaxis for prevention of bleeding episodes in patients with haemophilia A (HA) with and without inhibitors. While low bleeding rates were observed in clinical trials, patients still experience breakthrough bleeds (BTBs) with emicizumab in the real‐world. Current guidelines recommend use of recombinant activated factor VII (rFVIIa) for treatment of BTBs in patients with inhibitors. Due to thrombotic events observed in the HAVEN 1 study, activated prothrombin complex concentrate (aPCC) should be used with caution.ObjectivesThe objective of this review is to identify and discuss real‐world data on the frequency of BTBs and the safety of concomitant rFVIIa use in patients with inhibitors on emicizumab prophylaxis.MethodsA search of the following databases was conducted on 15 July 2022: BIOSIS Previews®, Current Contents Search®, Embase®, MEDLINE®. Search terms included ‘real world’, ‘haemophilia A’, and ‘emicizumab’.Results and conclusionsEleven relevant publications were identified (seven original research articles and four congress abstracts). The frequency of BTBs specifically for HA patients with inhibitors was described in three publications with 5%–56% patients on emicizumab reporting ≥1 bleeding episode. Treatment of these BTBs appeared to be managed according to relevant guidelines. Importantly, no thrombotic complications occurred during concomitant rFVIIa use. Due to the nature of real‐world studies, direct comparison of the results between studies is limited. However, real‐world data show that BTBs in inhibitor patients during emicizumab prophylaxis can be safely treated with rFVIIa.

Publisher

Wiley

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