Red cell exchange transfusions increase cerebral capillary transit times and may alter oxygen extraction in sickle cell disease.

Persons with sickle cell disease (SCD) suffer from chronic hemolytic anemia, reduced blood oxygen content, and lifelong risk of silent and overt stroke. Major conventional stroke risk factors are absent in most individuals with SCD, yet nearly 50% have evidence of brain infarcts by age 30 years, indicating alternative etiologies for ischemia. We investigated whether radiological evidence of accelerated blood water transit through capillaries, visible on arterial spin labeling (ASL) MRI, reduces following transfusion-induced increases in hemoglobin and relates to oxygen extraction fraction (OEF). Neurological evaluation along with anatomical and hemodynamic imaging with cerebral blood flow (CBF)-weighted pseudocontinuous ASL and OEF imaging with T 2 -relaxation-under-spin-tagging (TRUST) were applied in sequence before and after blood transfusion therapy (n=32) and in a comparator cohort of non-transfused SCD participants on hydroxyurea therapy scanned at two time points to assess stability without interim intervention (n=13). OEF was calculated separately using models derived from human hemoglobin-F, hemoglobin-A, and hemoglobin-S. Gray matter CBF and dural sinus signal, indicative of rapid blood transit, were evaluated at each time point and compared to OEF using paired statistical tests (significance: two-sided p<0.05). No significant change in sinus signal was observed in non-transfused participants (p=0.650), but a reduction was observed in transfused participants (p=0.034), consistent with slower red cell transit following transfusion. The dural sinus signal intensity was inversely associated with OEF pre-transfusion (p=0.011), but not post-transfusion. Study findings suggest that transfusion-induced increases in total hemoglobin may lengthen blood transit times through cerebral capillaries and alter cerebral OEF in SCD.