Abstract
In patients with sickle cell disease (SCD), cerebral blood flow (CBF) is elevated to counteract anemia and maintain oxygen supply to the brain. This may exhaust the vasodilating capacity of the vessels, possibly increasing the risk of silent cerebral infarctions (SCI). To further investigate cerebrovascular hemodynamics in SCD patients, we assessed CBF, arterial transit time (ATT), cerebrovascular reactivity of CBF and ATT (CVRCBF and CVRATT) and oxygen delivery in patients with different forms of SCD and matched healthy controls. We analyzed data of 52 patients with severe SCD (HbSS and HbSβ0-thal), 20 patients with mild SCD (HbSC and HbSβ+-thal) and 10 healthy matched controls (HbAA and HbAS). Time-encoded arterial spin labeling (ASL) scans were performed before and after a vasodilatory challenge using acetazolamide (ACZ). To identify predictors of CBF and ATT after vasodilation, regression analyses were performed. Oxygen delivery was calculated and associated with hemoglobin and fetal hemoglobin (HbF) levels. At baseline, severe SCD patients showed significantly higher CBF and lower ATT compared to both the mild SCD patients and healthy controls. As CBFpostACZ was linearly related to CBFpreACZ, CVRCBF decreased with disease severity. CVRATT was also significantly affected in severe SCD patients compared to mild SCD patients and healthy controls. Considering all groups, women showed higher CBFpostACZ than men (p < 0.01) independent of baseline CBF. Subsequently, post ACZ oxygen delivery was also higher in women (p < 0.05). Baseline, but not post ACZ, GM oxygen delivery increased with HbF levels. Our data showed that baseline CBF and ATT and CVRCBF and CVRATT are most affected in severe SCD patients and to a lesser extent in patients with milder forms of SCD compared to healthy controls. Cerebrovascular vasoreactivity was mainly determined by baseline CBF, sex and HbF levels. The higher vascular reactivity observed in women could be related to their lower SCI prevalence, which remains an area of future work. Beneficial effects of HbF on oxygen delivery reflect changes in oxygen dissociation affinity from hemoglobin and were limited to baseline conditions suggesting that high HbF levels do not protect the brain upon a hemodynamic challenge, despite its positive effect on hemolysis.
Highlights
Sickle cell disease (SCD) is an inherited form of hemolytic anemia causing widespread organ damage including stroke (Rees et al, 2010; Debaun and Kirkham, 2016)
We demonstrated that during a vasodilatory challenge cerebral blood flow (CBF) and white matter (WM) ATT are mainly determined by the baseline vascular state
CVRCBF and CVRATT were increasingly affected by, genotype based, disease severity, which was explained by its effect on baseline CBF and ATT
Summary
Sickle cell disease (SCD) is an inherited form of hemolytic anemia causing widespread organ damage including stroke (Rees et al, 2010; Debaun and Kirkham, 2016). To counteract anemia and maintain oxygen delivery to the brain, resting cerebral blood flow (CBF) is elevated in patients with SCD (Numaguchi et al, 1990; Oguz et al, 2003; Bush et al, 2016) This compensatory mechanism partially limits the ability to respond to hemodynamic stress, since arterioles and capillaries are already close to maximum vasodilation (Václavuet al., 2019), potentially leaving SCD patients at risk to acute changes in hemoglobin levels or nocturnal desaturation (DeBaun et al, 2012a). SCIs are surprisingly common in patients with milder forms of SCD such as HbSC and HbSβ+-thalassemia (HbSβ+-thal), with a prevalence of SCIs in up to 37% of the patients (Zafeiriou et al, 2004; DeBaun et al, 2012a; Guilliams, 2015), little is known about cerebral hemodynamics in patients with milder forms of SCD
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