Management and outcomes of paediatric patients on emicizumab prophylaxis undergoing surgical procedures: Experience from a large haemophilia centre in the UK

Abstract

Dear Editor, Emicizumab (Hemlibra) is the first commercially available non-factor replacement for patients with haemophilia A (PwHA).1 It is a bispecific humanized monoclonal antibody that bridges activated factor (F) IX and FX and improves haemostasis through replacing the missing function of activated FVIII.2 Paediatric population with haemophilia usually have central venous access devices (CVAD) to receive prophylactic infusions of clotting factor to prevent bleeding. In the emicizumab era, CVAD devices removal is a common procedure as venous infusions are no longer needed and are replaced by subcutaneous injections.3 However, there is no consensus on the appropriate management of CVAD removals or other surgical procedures in patients on this novel agent.4 The safety and efficacy of emicizumab prophylaxis in PwHA have been demonstrated in HAVEN clinical trials programme.5–8 Although minor and unplanned major surgical procedures did occur during HAVEN trials, patients were managed according the investigator’s decision.3 This letter presents real world experience of management and outcomes of paediatric PwHA with and without inhibitors who underwent surgical procedures while on emicizumab prophylaxis in a large comprehensive haemophilia centre in the United Kingdom. We performed retrospective study based on the data of all haemophilia A patients on emicizumab prophylaxis, treated at the haemophilia unit at BirminghamChildren’s Hospital. Patients between 1 and 16 years old who underwent surgery between February 2018 and January 2021 were included. Data were collected from participants’ medical records. It included demographic data, medical history, baseline FVIII levels, FVIII inhibitor status, date of start of emicizumab, emicizumab dosing and frequency, type of surgery, peri-operative management, planned and unplanned peri-operative use of recombinant(r) FVIII/bypassing agents and any antifibrinolytic agents, as well as any treatment planmodifications. Information regarding procedurerelatedbleedingwas also collected. Adverse events andnumber of hospitalization days were recorded. Altogether, data of 13 patients were included. Their characteristics and surgical information are presented in Table 1. Their age ranged from 0.72 to 13.20 (Median [Interquartile range] 6.6 [3.7–8.15]) years. All patients had severe haemophilia A with factor level <1% activity. Three patients had active FVIII inhibitors prior to surgery with levels of 491 Bethesda units (BU), 8.5 BU and 3.0 BU. At time of surgery, all patients were on emicizumab for a period ranging from 2 to 62 weeks (Median [Interquartile range] 38.0 [18.79–54.57]), and dose of 3 mg/kg every 2 weeks except patient#12who was on the weekly loading doses, number of doses prior to surgery ranged 2–35 doses(Median (Interquartile range) 23.0 (14.0–30.0)). Overall, 13 procedures were performed (12 surgical and one dental). According to Santagostino et al.9 definition; 12 surgical procedures where considered minor in which only skin, mucous membranes, or superficial connective tissue were manipulated while the cleft palate correction was considered amajor surgery. Peri-operative haemostatic planning for these children involved multidisciplinary teamconsensus among thehaematology team, anaesthesiologists and surgeons/proceduralists. All procedures were managedwith pre-planned antifibrinolytic (tranexamic acid)