Author(s): Cathy Buranahirun, PsyD, Keck School of Medicine, University of Southern California/Childrens Hospital Los Angeles; Christine Mrakotsky, PhD, Boston Childrens Hospital/Harvard Medical School; Cara Hannemann, PsyD, Indiana Hemophilia and Thrombosis Center; David L. Cooper, MD, MBA, Novo Nordisk Inc.; Greta N. Wilkening, PsyD, PhD, Childrens Hospital Colorado; Kevin A. Shapiro, MD, PhD, Cortica Healthcare; Karin S. Walsh, PsyD, Childrens National Hospital; Milan Geybels, PhD, Novo Nordisk A/S; Madhvi Rajpurkar, MD, Carman and Ann Adams Department of Pediatrics, Childrens Hospital of Michigan/Wayne State University; Pamela Ventola, PhD, Cogstate; Stacy E. Croteau, MD, MMS, Boston Childrens Hospital/Harvard Medical School

Research Category: Clinical Research/Clinical Trials

Description:

Objective:

Studies from the 1980s and 1990s in children with hemophilia demonstrated a negative impact of the disease on cognition. Reduction in HIV and hepatitis C burden along with recent improvements in the standard of care for hemophilia may have changed the ways in which hemophilia affects cognitive development, but this is not well understood. The eTHINK study was designed to assess more current effects of hemophilia on cognitive development and to establish a normative data set for cognitive function in children with hemophilia receiving the current standard of care.

Methods:

Males with congenital hemophilia A or B of any severity, aged 1 to 21 years, were eligible for this study. All participants underwent a neurological examination, neuropsychological assessment, and provided both hemophilia and developmental history. The assessment battery included standardized tests of developmental (Bayley-III) or intellectual (WPPSI-IV/WASI-II) function, tests of processing speed and attention (Cogstate Computerized Battery), and parent- and self-reported ratings of executive function (BRIEF-P/2/-A), emotional/behavioral adjustment (BASC-3), and adaptive skills (ABAS-3). Raw scores for each instrument were converted to z scores for comparison against normative data from the general US population.

Summary:

A total of 551 males with hemophilia A (n=443) or B (n=101) classified as mild (n=98), moderate (n=103), or severe (n=333) were enrolled in the study. Performance on tests of overall intelligence (IQ), behavior, attention, and processing speed for patients with hemophilia were mostly comparable to age-matched normal population. In contrast, patients with hemophilia and their parents reported more difficulty with adaptive skills and executive function in daily life. Older adolescents and young adults with hemophilia reported poorer behavioral adjustment; behavioral/emotional function scores were lower for those with hemophilia compared with the general population. Adaptive skills may differ between patients with different disease severities, as parent-reported independence tended to be lower in patients with mild hemophilia compared with patients with severe hemophilia.

Conclusions:

Overall, young males with hemophilia in this cohort performed well within age expectation on standardized cognitive tests in the clinical setting. However, some may be at higher risk of experiencing difficulties with executive function and adaptive skills within the context of their daily lives.