According to results published in the American Journal of Hematology, lower hemoglobin levels appear to be associated with reduced white matter volume throughout the brain, regardless of patients’ sickle cell disease (SCD) status. Thus, the severity of anemia, not disease state, predicts white matter volume.

The study took place at Children’s Hospital Los Angeles in California, and the investigators hypothesized that differences in white matter volume loss could be explained by hemoglobin levels and would correlate with cognitive performance, quantified as a Full Scale Intelligence Quotient. Magnetic resonance imaging (MRI) was performed to identify voxelwise changes in white matter brain volumes to compare with hemoglobin levels to determine what brain regions may be susceptible to anemia.

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In total, there were 118 participants: 52 patients with clinically asymptomatic SCD (mean age ± standard deviation [SD], 21.4 ± 7.7 years; 27 female patients; mean hemoglobin ± SD, 9.6 ± 1.6 g/dL), 26 patients with non-SCD anemia (mean age ± SD, 23.9 ± 7.9 years; 14 female patients; mean hemoglobin ± SD, 10.8 ± 2.5 g/dL), and 40 control participants (mean age ± SD, 27.7 ± 11.3 years; 28 female patients; mean hemoglobin ± SD, 13.4 ± 1.3 g/dL).

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Regional white matter volume was correlated with anemia severity in all 3 patient groups, and brain volumes were independent of disease status after controlling for age, sex, and hemoglobin level. Both white matter volume loss and an abnormal burden of silent cerebral infarctions (> 1 per decade of life) were associated with lower cognitive performance (r2 = 0.18; P =.0048) and the number of silent cerebral infarctions (P =.029) in male patients but not in female patients, indicating a sexually dimorphic response to chronic anemia. Hemoglobin levels and cognitive measures were similar between participants with and without silent cerebral infarctions.

The authors concluded that “the overlap in findings between SCD and anemic-control groups suggests that the neurological injury patterns commonly found in patients [with SCD] are primarily due to their low hemoglobin levels rather than abnormal red blood cell morphology.” Furthermore, they stated, “the spatial distribution of volume loss suggests chronic hypoxic cerebrovascular injury, despite compensatory hyperemia.”


1.     Choi S, O’Neil SH, Joshi AA, et al. Anemia predicts lower white matter volume and cognitive performance in sickle and non‐sickle cell anemia syndrome [published online July 1, 2019]. Am J Hematol. doi:10.1002/ajh.25570