For patients with sickle cell disease (SCD), response to acetazolamide (ACZ) is mainly determined by baseline measures of cerebral blood flow (CBF) and arterial transit time (ATT), according to research published in Frontiers in Physiology.

Patients with SCD often have elevated resting CBF to counteract anemia and maintain oxygen flow to the brain. The study authors sought to understand the cerebral hemodynamics of patients with severe and milder forms of SCD.

The authors measured CBF, ATT, oxygen delivery at rest, and oxygen delivery after ACZ treatment using time-encoded arterial spin labeling (ASL) MRI. The study included data from 52 patients with severe SCD and 20 with mild SCD and compared them to 10 patients without SCD as controls.

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The authors found 2 factors that appeared as modulators of ACZ response: female sex and fetal hemoglobin (HbF) levels. Female patients were more likely to have robust increases in gray matter CBF and oxygen delivery after ACZ. Female patients also had shortening of white matter ATT after ACZ. This suggested that female patients may have stronger cerebrovascular reactivity with ACZ than male patients.

These results may explain why silent cerebral infarctions (SCIs) are less common in female patients with SCD, but the current analysis was underpowered to make conclusions about the effects of sex on cognitive outcomes.

Increasing HbF percentage was associated with an increase in resting CBF and oxygen delivery in gray matter. HbF levels had no effect on peak oxygen delivery.

ACZ administration consistently shortened ATT in gray matter and white matter in this study and CBF increased in all groups. Patients with mild vs severe SCD in white matter had significantly different cerebrovascular reactivity (CVR) of ATT.

CVR of ATT and CVR of CBF were affected by disease severity. Patients with severe SCD had shorter baseline ATT than patients with milder disease and controls.

Some conclusions from the study were limited. It is difficult to measure CBF in white matter using ASL, which could explain why the authors didn’t find differences in CVR of CBF between groups. Mismatch in the number of patients with severe disease vs mild disease also make it challenging to draw conclusions based on disease severity.

After correcting for baseline effects, female sex remained the dominant predictor for vasodilation and response to ACZ.


Afzali-Hashemi L, Baas KPA, Schrantee A, et al. Impairment of cerebrovascular hemodynamics in patients with severe and milder forms of sickle cell disease. Front Physiol. 2021;12:645205. doi:10.3389/fphys.2021.645205