Abstract 35: Transfusion Relieves Cerebral Metabolic Stress in Children with Sickle Cell Disease

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Abstract

Introduction: Transfusions (Tx) are the mainstay of stroke prevention in children with sickle cell disease (SCD), but the pathophysiology conferring this neuroprotection is not well understood.

Hypothesis: Tx relieves cerebral metabolic stress by improving arterial oxygen content, thereby lowering chronically-elevated cerebral blood flow (CBF) and oxygen extraction fraction (OEF) in children with SCD at risk for stroke.

Methods: Children with SCD on chronic Tx therapy underwent two brain MRIs with measurement of CBF via pseudocontinuuous arterial spin labeling and OEF via asymmetric spin echo sequence within 24 hours of exchange Tx. To determine how Tx may reduce regions of elevated OEF, we set absolute OEF thresholds (45, 47.5, 50%) and compared tissue volumes above each threshold pre- and post-Tx using nonparametric paired statistics.

Results: Twelve children with SCD (6-21 yrs) underwent MRIs. Tx raised Hb and lowered CBF and OEF (Figure), suggesting that elevated CBF and OEF may be markers of metabolic stress relieved by Tx. While CBF correlates with age in healthy children, pre-Tx CBF correlation with age was lost (τ= -0.42, p=0.07), but regained post-Tx (τ= -0.76, p=0.001). Also, absolute change in OEF diminished with increasing age (τ=. -0.75, p=0.003). Regions with very high OEF were found in the periventricular white matter, a common area of infarcts in SCD (Figure, average OEF maps pre- and post-Tx). Tx reduced the volume of these brain regions defined by all three OEF thresholds (Table), suggesting that Tx reduces brain regions at high risk for stroke.

Conclusion: Tx in SCD children improves arterial oxygen content by increasing Hb, allowing CBF and OEF to fall, thus relieving metabolic stress globally and regionally. The absolute change in OEF correlates with age, suggesting that the efficacy of Tx may be age-dependent.

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