Abstract T P370: Blood Transfusions in Pediatric Sickle Cell Disease Normalize Cerebral Blood Flow While Maintaining Constant Cerebral Oxygen Metabolism

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Background: Chronic blood transfusions (Tx) reduces stroke risk in pediatric sickle cell disease (SCD). Cerebral blood flow (CBF) is elevated in SCD, likely representing a compensatory mechanism to maintain cerebral oxygen metabolism (CMRO2) in the setting of reduced arterial oxygen content (CaO2) from chronic anemia. When exhausted compensatory mechanisms are unable to meet oxygen demands, stroke ensues. We measured MR-derived CBF and oxygen extraction fraction (OEF) pre- and post-Tx, hypothesizing that Tx ‘resets’ the CBF baseline by increasing CaO2 via increased hemoglobin (Hb), while maintaining cerebral oxygen delivery and metabolism. Methods: SCD children on chronic Tx were enrolled in a prospective, observational MRI study. MR-CBF and MR-OEF were acquired before and 2 hours after exchange Tx. MR-CBF and MR-OEF were measured using pseudocontinuous arterial spin labelling and a novel asymmetric spin echo sequence, respectively. CaO2 =1.35 x [Hb] x SaO2. CMRO2 = CaO2 x CBF x OEF. Results: Two SCD children underwent MRI pre- and post-Tx (six more are anticipated prior to ISC). For subject #1 (18 yo F with overt stroke), mean global CBF was 128 and 98 ml/min/100g pre- and post-Tx, respectively, indicating a 24% CBF reduction. For subject #2 (6 yo F with elevated transcranial Doppler velocities), mean global CBF was 189 and 129 ml/min/100g pre- and post-Tx, respectively, a 32% CBF reduction (Fig). Both Hb and CaO2 were increased after Tx, resulting in unchanged oxygen delivery (CaO2 x CBF) post-Tx. Moreover, OEF and CMRO2 were not significantly different pre- and post-Tx, consistent with our hypothesis that CBF increases to maintain oxygen delivery. Conclusions: Elevated CBF is likely a compensatory mechanism to maintain constant oxygen delivery in SCD children who have chronically low CaO2. In our subjects, Tx improved CaO2, allowing CBF to normalize. This reduced hemodynamic stress likely contributes to the lower stroke risk in chronically transfused SCD children.