Practical Guidance of the GTH Haemophilia Board on the Use of Emicizumab in Patients with Haemophilia A

Abstract

Emicizumab has been approved for bleeding prophylaxis in patients with haemophilia A (PWHAs) with or without inhibitors. Because of substantial differences between factor VIII (FVIII) and Emicizumab, the ‘Ständige Kommission Hämophilie’ of the German, Austrian, Swiss Society for Thrombosis and Haemostasis Research (GTH) established a practical guidance for the use of Emicizumab in PWHAs. A systematic literature research was conducted in PubMed. Based on this and on personal experience, this practical guidance has been developed. Each single statement has been discussed among members of the ‘Ständige Kommission Hämophilie’ and revised accordingly. The final set of recommendations has been approved by all authors analogous to the Delphi method. This practical guidance is provided for physicians treating PWHAs with regard to general aspects, patient education, bleeding treatment, surgery, use of Emicizumab in previously untreated patients (PUPs), patients with newly diagnosed inhibitors and elderly patients. Patients should be treated in expert centres and adequate laboratory tests to monitor Emicizumab levels, FVIII replacement and inhibitors should be available. Early experience of immune tolerance induction protocols integrating Emicizumab is reviewed, and the limited experience in PUPs and very young children is described. So far, no thromboembolic complications have been reported with the concomitant use of FVIII or recombinant activated FVII for bleeding treatment or surgery. Activated prothrombin complex concentrate doses of >100 U/kg for >24 hours should be avoided whenever possible because of the high risk of thrombosis and/or thrombotic microangiopathy. In conclusion, this study is designed to support haemophilia physicians using Emicizumab in physicians treating hemophilia and using (PWHAs). With further post-marketing experience and trials, regular updates are necessary.

Managing invasive procedures in haemophilia patients with limited resources, extended half‐life concentrates or non‐replacement therapies in 2022

“…49 Since then, guidelines have been implemented to recommend rFVIIa use as first line concomitant bypassing therapy in patients on emicizumab prophylaxis and, if possible, avoid aPCC or use it at the lowest doses for the management of breakthrough bleeds and/or invasive procedures. [54][55][56][57][58][59] On the other hand, no thrombotic adverse events have been described in patients without inhibitors receiving FVIII concentrates at standard doses in association with emicizumab prophylaxis. This might be related to the 10fold higher affinity of FVIII for FIX and FX substrates which results in a transient displacement of emicizumab without additive haemostatic effect.…”

“…During the phase 3 study, thrombotic events including thrombotic microangiopathy (TMA) were observed in five inhibitor patients who received concomitant high doses of aPCC (> 100 U/kg per day, > 24 h) to treat breakthrough bleeds 49 . Since then, guidelines have been implemented to recommend rFVIIa use as first line concomitant bypassing therapy in patients on emicizumab prophylaxis and, if possible, avoid aPCC or use it at the lowest doses for the management of breakthrough bleeds and/or invasive procedures 54–59 . On the other hand, no thrombotic adverse events have been described in patients without inhibitors receiving FVIII concentrates at standard doses in association with emicizumab prophylaxis.…”

Emicizumab for All Pediatric Patients with Severe Hemophilia A

“…If a perioperative treatment with aPCC is necessary for an elective major surgery, a withdrawal of emicizumab treatment could be considered for at least 6 months before surgery. 38…”

Disruptive technology and hemophilia care: The multiple impacts of emicizumab

“…With unusual speed and stimulated by promising results of clinical studies and a variety of consensus and expert opinions, 13,[18][19][20] emicizumab has rapidly replaced conventional bypassing agents for patients with inhibitors and is recognized as the prophylactic agent of choice for these individuals. In a recent survey performed by the European Association for Haemophilia and Allied Disorders involving 32 European HTCs, emicizumab was found to be the prophylactic agent of choice used in 69% of patients with hemophilia A with inhibitors (unpublished).…”