The observed rates of intracranial hemorrhaging (ICH) in patients with hemophilia were higher compared to the general populations among all age groups examined, according to a meta-analysis of studies reported online ahead of print in Blood.
As previously reported, the risk seemed higher in the group of infants and toddlers, and neonates with hemophilia showed a 33-fold higher risk of ICH than newborns in the general population, in the current study.
The researchers performed a literature review and assessed 45 studies that represented 54,470 patients, 809,151 person-years and 5,326 live births of patients with hemophilia. Pooled ICH incidence and mortality were calculated for three age groups: persons of all ages with hemophilia; children and young adults below 25 years of age with hemophilia; and neonates with hemophilia.
Overall results
Among the persons of all ages, the pooled ICH incidence and mortality rates were 2.3 (95% confidence interval, 1.2-4.8) and 0.8 (95% CI, 0.5-1.2) per 1,000 person-years, respectively, according to the authors. They found that in children and young adults, the pooled ICH incidence and mortality rates were 7.4 (95% CI, 4.9-11.1) and 0.5 (95% CI, 0.3-0.9) per 1,000 person-years, respectively. In neonates, the pooled cumulative ICH incidence was 2.1% (95% CI, 1.5-2.8) per 100 live births and the pooled ICH cumulative mortality was 0.2% (95% CI, 0.0-1.2) per 100 live births.
Overall, the occurrence of ICH was classified as spontaneous in 35%-58% of cases.
Neonates at risk
The observed ICH rates in hemophilia were higher compared to the general populations among the age groups assessed. Neonates showed the highest risk of ICH, which is confirmed by other studies in severe hemophilia demonstrating that neonates were at 11.2 times higher risk for ICH compared with 1- to 12-month-old children, and is also strongly increased compared to neonates in the general populations, the researchers stated.
A previous large study of term infants reported 361 intracranial bleeding episodes per 583,340 live births (0.062% per 100 live births), and comparing this to the current pooled estimate of 2.1% per 100 live births, neonates with hemophilia showed a 33-fold higher risk of ICH than newborns in the general population, according to the researchers.
Monitoring and follow-up
“Our findings suggest that adequate follow-up and monitoring of patients is warranted among all ages, especially in the presence of risk factors. Prophylaxis seems to halve ICH risk in children and adults with severe hemophilia, which supports existing recommendations encouraging early initiation of prophylactic treatment,” the authors advised.
Accurate capture of the true frequency of ICH is challenged by considerable clinical heterogeneity, limiting the precision and generalizability of the pooled estimates, leading to the likelihood that ICH and mortality were underdiagnosed in this analysis, according to the authors.
“We found high ICH incidence and mortality rates in patients with hemophilia. Our findings suggest that ICH is still an important problem in hemophilia requiring adequate counseling of patients of all ages,” the researchers concluded.
This work was supported by a grant from Sobi. Some of the authors reported research, consulting or lecturing fees from a variety of pharmaceutical companies, including Sobi.