Intracranial haemorrhage in children and adolescents with severe haemophilia A or B – the impact of prophylactic treatment

Abstract

The discussion of prophylactic therapy in haemophilia is largely focused on joint outcomes. The impact of prophylactic therapy on intracranial haemorrhage (ICH) is less known. This study aimed to analyse ICH in children with haemophilia, with a focus on different prophylaxis regimens and sequelae of ICH. We conducted a multicentre retrospective and prospective study that included 33 haemophilia centres from 20 countries. Inclusion criteria were children and adolescents born between 1993 and 2014, with severe haemophilia A or B without inhibitors. Participants were categorized by prophylaxis regimen: full, partial or none, based on dose and dose frequency of regular infusions. The cohort study included 1515 children: 29 cases of ICH over 8038 patient years were reported. The incidence of ICH in the prophylaxis group, 0·00033 cases of ICH/patient year, was significantly lower compared to the no prophylaxis group, 0·017 cases of ICH/patient year (RR 50·06; P < 0·001) and the partial prophylaxis group, 0·0050 cases of ICH/patient year (RR 14·92; P = 0·007). In the on-demand-group, 8% (2/24) children with ICH died and 33% had long-term sequelae, including intellectual and behavioural problems, paresis and epilepsy. Children on regular, frequent prophylaxis have a low risk of ICH compared to those using non-frequent or no prophylaxis.

Intracranial haemorrhage in children with inherited bleeding disorders in the UK 2003‐2015: A national cohort study

“…Zanon et al reported that severe haemophilia was associated with an age adjusted hazard ratio of 10.21, with the majority of bleeds in mild haemophilia occurring not in children but in older adults. The paucity of ICH in children with mild haemophilia in this UK cohort suggests that baseline factor activity in mild‐moderate disease not only reduces the risk of joint bleeding but may also offer protection against ICH, emphasizing the potential protective effect of routine prophylaxis …”

“…Intracranial haemorrhage has been estimated to occur in 3%‐4% of neonates with haemophilia and has been associated with trauma at delivery, leading to debate on the optimal mode of delivery . The incidence of ICH in older children with haemophilia has been estimated previously at 2.02‐7.96 per 1000 patient years, but is less well defined in the modern era where, at least in the developed world, prophylaxis commenced early in childhood is widespread and may offer protection against all types of bleeding . In addition, published reports have varied significantly in terms of age inclusion criteria which may affect risk factor identification in specific age groups.…”

Mortality of patients with haemophilia in Brazil: First report

“…It is tempting to suggest that this might result from the implementation of early primary prophylaxis for severe haemophilia on this age group. Andersson et al recently reported that children on regular, frequent prophylaxis have a lower risk of intracranial haemorrhage compared with those using non‐frequent or no prophylaxis . However, since the present study was not designed to investigate the impact of health policies on the outcome measurements, further studies will be needed to confirm this.…”

Achieving the unimaginable: Health equity in haemophilia

“…establishment of HTCs, integrated care models, organization of blood banking resources, etc). 13,14 Even among non-severe PwH, risk for death from intracranial bleeding is 3.5-fold higher than in the general population 15 -further emphasizing the need for improved protection even among those with mild haemophilia. 13,14 Even among non-severe PwH, risk for death from intracranial bleeding is 3.5-fold higher than in the general population 15 -further emphasizing the need for improved protection even among those with mild haemophilia.…”