Unwinding the path from anemia to stroke

Wood, John C.

doi:10.1182/blood-2018-01-824185

Cited by 2 publications

(2 citation statements)

References 9 publications

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“…18,37–39 We and others have proposed that in some patients these increases in CBF could result in a paradoxical decrease in oxygen availability to brain tissue through capillary shunting. 23,35,40 As oxygen offloading to tissue is dependent in part on the amount of time blood water spends in capillaries, shortened capillary transit times could cause lower oxygen extraction. Such effects could result in a state of chronic mild tissue hypoxia that leads to brain lesions.…”

Section: Discussionmentioning

confidence: 99%

Reduced oxygen extraction efficiency in sickle cell anemia patients with evidence of cerebral capillary shunting

Juttukonda

Donahue

Waddle

et al. 2020

J Cereb Blood Flow Metab

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Arterial spin labeling (ASL) magnetic resonance imaging (MRI) utilizes arterial blood water as an endogenous contrast agent to provide a quantitative measure of cerebral blood flow (CBF). Recently, hyperintense signal within dural venous sinuses in ASL images of sickle cell anemia (SCA) patients has been shown to be consistent with elevated flow velocities and may indicate capillary shunting and reduced oxygen extraction. Here, we performed oxygen extraction fraction (OEF) and CBF measurements in adults (cumulative n = 114) with ( n = 69) and without ( n = 45) SCA to test the hypothesis that hyperintense venous ASL signal is associated with reduced OEF. Higher categorical scores of shunting on ASL MRI were associated with lower OEF in participants with silent cerebral infarcts or white matter hyperintensities ( p = 0.003), but not in those without lesions ( p = 0.551). These findings indicate that venous hyperintense signal in ASL images in SCA patients may represent a marker of capillary-level disturbances in oxygen exchange efficiency and small vessel pathology.

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Section: Discussionmentioning

confidence: 99%

Reduced oxygen extraction efficiency in sickle cell anemia patients with evidence of cerebral capillary shunting

Juttukonda

Donahue

Waddle

et al. 2020

J Cereb Blood Flow Metab

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“…These paradoxical findings may be explained in the context of preliminary reports of venous hyperintensities on arterial-spin labeling MRI, consistent with arterio-venous shunting (253). One theory, named the “functional shunting hypothesis” (254), postulates that regional shunting pathophysiology, coupled with compensatory increases in global CBF and reductions in arterial transit times and CVR, lead to regions of impaired oxygen unloading and diffusion in SCD, reflected by regional reductions in OEF. In these instances, tissue oxygen delivery may be compromised even though differences between arterial and venous saturation are small.…”

Section: Hemodynamic Compromisementioning

confidence: 99%

Vascular Instability and Neurological Morbidity in Sickle Cell Disease: An Integrative Framework

et al. 2019

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It is well-established that patients with sickle cell disease (SCD) are at substantial risk of neurological complications, including overt and silent stroke, microstructural injury, and cognitive difficulties. Yet the underlying mechanisms remain poorly understood, partly because findings have largely been considered in isolation. Here, we review mechanistic pathways for which there is accumulating evidence and propose an integrative systems-biology framework for understanding neurological risk. Drawing upon work from other vascular beds in SCD, as well as the wider stroke literature, we propose that macro-circulatory hyper-perfusion, regions of relative micro-circulatory hypo-perfusion, and an exhaustion of cerebral reserve mechanisms, together lead to a state of cerebral vascular instability. We suggest that in this state, tissue oxygen supply is fragile and easily perturbed by changes in clinical condition, with the potential for stroke and/or microstructural injury if metabolic demand exceeds tissue oxygenation. This framework brings together recent developments in the field, highlights outstanding questions, and offers a first step toward a linking pathophysiological explanation of neurological risk that may help inform future screening and treatment strategies.

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Unwinding the path from anemia to stroke

Cited by 2 publications

References 9 publications

Reduced oxygen extraction efficiency in sickle cell anemia patients with evidence of cerebral capillary shunting

Reduced oxygen extraction efficiency in sickle cell anemia patients with evidence of cerebral capillary shunting

Vascular Instability and Neurological Morbidity in Sickle Cell Disease: An Integrative Framework

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