Intracranial hemorrhage (ICH) is one of the most significant bleeding complications in hemophilia with a reported 20% mortality rate. A recent study from the Centers for Disease Control and Prevention Universal Data Collection project demonstrated that prophylaxis in patients with severe hemophilia reduced the risk of intracranial hemorrhage but mortality remained high (19.6 %). However 95% of those ICH deaths occurred in subjects over 20 years of age. This was in contrast to prior studies that demonstrated much higher mortality rates in children. Additional studies are needed to confirm this shift in the age distribution of ICH mortality. The objective of this study was to determine the mortality rate from ICH in pediatric patients with hemophilia admitted to US tertiary care hospitals.
This retrospective multicenter cohort study utilized data from 43 free-standing children’s hospitals that contribute data to the Pediatric Health Information System administrative database. Subjects were male, less than 21 years of age, with an International Classification of Diseases (ICD-9) diagnostic code for hemophilia A or B, with an admission between 1/1/2002-12/31/2011. ICD-9 discharge codes were used to identify admissions during which an ICH was diagnosed. Subjects were classified as having an inhibitor if they received bypassing agents (either FEIBA or recombinant factor VIIa). Summary statistics include frequencies and percentages for categorical variables and median and interquartile range for continuous variables. Odds ratios (OR) with 95% confidence intervals were calculated using multivariable logistic regression to evaluate the strength of association between mortality and the presence of ICH, an inhibitor and hemophilia type (A versus B).
During the 10 year study period there were a total of 8,325 admissions in 3,133 individual male subjects with either hemophilia A or B. 80% (2,506) of the subjects had hemophilia A and 14.4% (451) had an inhibitor. The median number of admissions per subject was 1 (interquartile range 1-3). Overall mortality for the entire cohort was low at 0.7% (21 deaths). There were a total of 327 admissions with ICD-9 codes for ICH in 265 (8.5%) subjects. 12.8% (34) of subjects had more than 1 ICH event during the study period. The median age for ICH was 2.2 (interquartile range 0.6-7.3) years. The ICH mortality rate was 1.8% (6 deaths). This represents an 11 fold decrease from prior ICH mortality estimates of 20%. 50% (3) of subjects who died from ICH had an inhibitor. For the entire cohort, mortality was associated with the presence of ICH (5.6 OR (2.3-14)) and the presence of an inhibitor (3.1 OR (1.2-7.8)).
This retrospective cohort study utilizing an inpatient pediatric administrative database confirms that mortality from ICH in pediatric patients is significantly reduced from prior studies. In this cohort, mortality from ICH was quite low (1.8%), representing an 11 fold decrease from previous mortality estimates. Potential reasons for this reduction include the routine use of prophylaxis in pediatric patients with severe hemophilia, increased availability of factor concentrates and aggressive management of patients with hemophilia and suspected ICH.
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.
