Abstract Number: PB0962
Meeting: ISTH 2020 Congress
Theme: Hemophilia and Rare Bleeding Disorders » Hemophilia - Clinical
Background: Emicizumab has been prescribed in the UK for haemophilia A (HA) with inhibitors since February 2018 and for severe HA without inhibitors since July 2019. Long term safety has yet to be established.
Aims: A descriptive analysis of adverse events reported to the National Haemophilia Database (NHD) in UK patients treated with Emicizumab, February 2018 – January 2020.
Methods: UK haemophilia centres are required to report adverse events to the NHD. These are evaluated by the UKHCDO Co-morbidity Working Party. A descriptive review of events reported in Emicizumab treated patients is presented.
Results: There were 101 inhibitor and 71 non-inhibitor HA patients treated with Emicizumab for a median (IQR) of 13.1 (4.6-194); total 969 months and a median 2.0 (1.3-2.7), total 1080 months, respectively. Thrombotic microangiopathy and anti-drug antibodies were not reported. Three possible thrombotic events and two deaths were reported, described in tables 1 and table 2, respectively. Eight (4.5%) patients reported skin reactions: mild localised reactions in five (2.9%): systemic rash in two and increasingly severe, recurrent reactions leading to cessation of Emicizumab in one (0.6%). Small joint arthralgia was reported in two (1.2%) and GI symptoms in three (1.7%). Five (2.9%) reported headache occurring soon after dosing: mild and self-limiting in two; more severe requiring imaging in a further two and severe enough to require hospitalisation and drug cessation in one. Other reports included appendicitis (n=1) and osteonecrosis (n=1).
Conclusions: Continued follow-up is required to establish long-term safety, particularly in relation to thrombotic events. Headaches severe enough to require imaging are reported for the first time. Robust pharmacovigilance is required for all HA treatments to avoid reporting bias.
| Case | Age (years) | Event | Description | Contributory Risk Factors | Continued Emicizumab |
| 1 | 78 | NSTEMI* | Chest pain after first dose of Emicizumab associated with fever and hypotension. Troponin 227 ng/l, ECG normal. Angiography confirmed triple vessel disease but no acute thrombus. | Severe symptomatic IHD and port infection | Yes: without recurrent symptoms |
| 2 | 53 | Chronic SMA**thrombosis | Chronic SMA thrombosis identified on CT scan performed for long standing abdominal pain 15 months after starting Emicizumab. Collaterals were identified | Atherosclerosis with aortic calcification | Yes: without recurrent symptoms |
| 3 | 32 | Atypical cardiac event | Chest pain after third dose of Emicizumab associated with raised troponin >5000 ng/l and non-specific ECG changes. Normal CT angiography. | – | Stopped pending further investigation |
| *Non ST elevation myocardial infarction, **superior mesenteric artery | |||||
[Table 1: Description of possible thrombotic events]
| Case | Age | Cause of Death | Ante-mortem duration of Emicizumab treatment |
| 1 | 51 | Multi-organ failure complicating viral infection | 6 months |
| 2 | 27 | Intra-abdominal bleeding whilst on Emicizumab prophylaxis, with significantly delayed presentation to hospital, hypovolaemic shock and multiorgan failure | 6 months |
[Table 2: Causes of death]
To cite this abstract in AMA style:
Wall C, Hall G, Collins P, Makris M, Shapiro S, Liesner R, Harrison C, Maclean R, Mangles S, Benson G, Evans G, Sartain P, Hay C, UK National Haemophilia Database . Adverse Event Reporting in Haemophilia A Patients with and without Inhibitors Treated with Emicizumab: A Report from the Co-morbidity Working Party of the UK Haemophilia Centres Doctors´ Organisation (UKHCDO) [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/adverse-event-reporting-in-haemophilia-a-patients-with-and-without-inhibitors-treated-with-emicizumab-a-report-from-the-co-morbidity-working-party-of-the-uk-haemophilia-centres-doctors-organisa/. Accessed September 21, 2023.« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/adverse-event-reporting-in-haemophilia-a-patients-with-and-without-inhibitors-treated-with-emicizumab-a-report-from-the-co-morbidity-working-party-of-the-uk-haemophilia-centres-doctors-organisa/