Hemophilia Not Linked With Cognitive and Behavioral Outcomes in Children

Children with hemophilia have similar intellectual and behavioral development to their peers in the general population, but a new report finds certain age groups of children also exhibited higher rates of attention-related deficits.¹

Study authors Mrakotsky, et al noted that previous research has suggested that hemophilia had negative effects on patients’ cognition independent of other medical conditions.

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For instance, a 1998 study suggested that children with more severe hemophilia had lower levels of academic achievement.² A 2003 study also found that boys with hemophilia may be more likely than the general population to have attention-deficit/hyperactivity disorder (ADHD).³

However, Mrakotsky and colleagues noted that the standard of care for patients with hemophilia has changed significantly in recent decades.¹

“Historically, patients with hemophilia were treated with human plasma-derived clotting factor concentrates, leaving them susceptible to HIV infection due to contaminated factor products,” they wrote. But the use of viral inactivated factor concentrates has significantly reduced the risk of HIV infection in patients with hemophilia. The resulting reduction in viral burden—along with other improvements in hemophilia patient care—may have had an effect on the cognitive consequences of hemophilia.

The new study, which was published in The Journal of Pediatrics, aimed to see whether contemporary standards of care affected the risk of cognitive, behavioral, and adaptive deficits in children and young adults with hemophilia. 

The investigators enrolled 551 males between the ages of 1 and 21 who had either hemophilia A or B. Patients were allowed to enroll regardless of the severity of their hemophilia, and regardless of whether they were taking inhibitors. The participants underwent neurological and neuropsychiatric assessments, and their scores on those tests were compared with age-matched population norms from the United States.

Most of the patients in the study had hemophilia A (81.1%), and most had what was considered to be severe hemophilia (62.4%).

The investigators found that, in general, males with hemophilia had age-appropriate levels of intellectual, behavioral, and adaptive development. They also found no association between the type or severity of hemophilia and early development or cognitive function. One reason for the latter finding, they said, might be that people with moderate or severe hemophilia are more likely to closely monitor activities that increase their risk of injury, which in turn may decrease the association between disease severity and cognitive morbidity.

“It is also possible that increased treatment efficacy has effectively neutralized the developmental risks associated with more severe disease, presumably related to a historically higher burden of bleeds (including brain bleeds),” the authors wrote.

Still, Mrakotsky and colleagues did find that certain age cohorts of children with hemophilia had lower scores on measures of attention and processing speed than their peers without hemophilia. Specifically, they said, children ages 4 to 5 and adolescents ages 10 to 21 performed worse on those measures.

“Furthermore, adolescents and young adults and those with comorbid [ADHD] reported more adaptive and executive function problems in daily life,” they wrote. “Incidence of ADHD in adolescents (21%) was higher than expected in the general population.”

The investigators noted that finding underscores the importance of screening for ADHD and similar disorders in patients with hemophilia, in order to more quickly initiate any needed interventions. 

“This study established a normative data set for monitoring neurodevelopment in individuals with hemophilia and highlights the importance of screening and intervention for challenges with cognitive and adaptive skills in this population,” they concluded.

References

1. Mrakotsky C, Walsh KS, Buranahirun Burns C, et al. The eTHINK study: cognitive and behavioral outcomes in children with hemophilia. J Pediatr. Published online May 9, 2024. doi:10.1016/j.jpeds.2024.114089

2. Usner DW, Donfield SM, Sirois PA, Gomperts ED, Bale JF Jr, Mitchell WG. Hemophilia morbidity, cognitive functioning, and academic achievement. J Pediatr. 1998;133(6):782-787. doi:10.1016/s0022-3476(98)70151-9

3. Wodrich DL, Recht M, Gradowski M, Wagner L. Is attention deficit hyperactivity disorder over-represented among HIV-seronegative boys with haemophilia? Preliminary results from our centre. Haemophilia. 2003;9(5):593-597. doi:10.1046/j.1365-2516.2003.00790.x