TY - JOUR
T1 - Red cell exchange transfusions lower cerebral blood flow and oxygen extraction fraction in pediatric sickle cell anemia
AU - Guilliams, Kristin P.
AU - Fields, Melanie E.
AU - Ragan, Dustin K.
AU - Eldeniz, Cihat
AU - Binkley, Michael M.
AU - Chen, Yasheng
AU - Comiskey, Liam S.
AU - Doctor, Allan
AU - Hulbert, Monica L.
AU - Shimony, Joshua S.
AU - Vo, Katie D.
AU - McKinstry, Robert C.
AU - An, Hongyu
AU - Lee, Jin Moo
AU - Ford, Andria L.
N1 - Funding Information:
This work was supported by the Child Neurology Foundation (K.P.G.); the Pediatric Critical Care and Trauma Scientist Development Program from the National Institutes of Health (NIH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (K12 HD04734) (K.P.G.); Washington University St. Louis CTSA from the NIH, National Center for Advancing Translational Sciences (UL1 TR000448) (K.P.G. and M.E.F.); Hematology K12 (5K12H2087107) (M.E.F.); NIH, National Institute of Neurological Disorders and Stroke grants K23NS099472 (K.P.G.), R01NS085419 (J.-M.L.), and R01NS082561 (H.A.); NIH, National Heart, Lung, and Blood Institute grant R01HL129241 (A.L.F.); and NIH, Eunice Kennedy Shriver National Institute of Child Health and Human Development Intellectual and Developmental Disabilities Research Center at Washington University (U54 HD087011) (J.S.S.).
Publisher Copyright:
© 2018 by The American Society of Hematology.
PY - 2018/3/1
Y1 - 2018/3/1
N2 - Blood transfusions are the mainstay of stroke prevention in pediatric sickle cell anemia (SCA), but the physiology conferring this benefit is unclear. Cerebral blood flow (CBF) and oxygen extraction fraction (OEF) are elevated in SCA, likely compensating for reduced arterial oxygen content (CaO2). We hypothesized that exchange transfusions would decrease CBF and OEF by increasing CaO2, thereby relieving cerebral oxygen metabolic stress. Twenty-one children with SCA receiving chronic transfusion therapy (CTT) underwent magnetic resonance imaging before and after exchange transfusions. Arterial spin labeling and asymmetric spin echo sequences measured CBF and OEF, respectively, which were compared pre- and posttransfusion. Volumes of tissue with OEF above successive thresholds (36%, 38%, and 40%), as a metric of regional metabolic stress, were compared pre- and posttransfusion. Transfusions increased hemoglobin (Hb; from 9.1 to 10.3 g/dL; P < .001) and decreased Hb S (from 39.7% to 24.3%; P < .001). Transfusions reduced CBF (from 88 to 82.4 mL/100 g per minute; P 5 .004) and OEF (from 34.4% to 31.2%; P < .001). At all thresholds, transfusions reduced the volume of peak OEF found in the deep white matter, a location at high infarct risk in SCA (P < .001). Reduction of elevated CBF and OEF, both globally and regionally, suggests that CTT mitigates infarct risk in pediatric SCA by relieving cerebral metabolic stress at patient- and tissue-specific levels.
AB - Blood transfusions are the mainstay of stroke prevention in pediatric sickle cell anemia (SCA), but the physiology conferring this benefit is unclear. Cerebral blood flow (CBF) and oxygen extraction fraction (OEF) are elevated in SCA, likely compensating for reduced arterial oxygen content (CaO2). We hypothesized that exchange transfusions would decrease CBF and OEF by increasing CaO2, thereby relieving cerebral oxygen metabolic stress. Twenty-one children with SCA receiving chronic transfusion therapy (CTT) underwent magnetic resonance imaging before and after exchange transfusions. Arterial spin labeling and asymmetric spin echo sequences measured CBF and OEF, respectively, which were compared pre- and posttransfusion. Volumes of tissue with OEF above successive thresholds (36%, 38%, and 40%), as a metric of regional metabolic stress, were compared pre- and posttransfusion. Transfusions increased hemoglobin (Hb; from 9.1 to 10.3 g/dL; P < .001) and decreased Hb S (from 39.7% to 24.3%; P < .001). Transfusions reduced CBF (from 88 to 82.4 mL/100 g per minute; P 5 .004) and OEF (from 34.4% to 31.2%; P < .001). At all thresholds, transfusions reduced the volume of peak OEF found in the deep white matter, a location at high infarct risk in SCA (P < .001). Reduction of elevated CBF and OEF, both globally and regionally, suggests that CTT mitigates infarct risk in pediatric SCA by relieving cerebral metabolic stress at patient- and tissue-specific levels.
UR - http://www.scopus.com/inward/record.url?scp=85047733115&partnerID=8YFLogxK
U2 - 10.1182/blood-2017-06-789842
DO - 10.1182/blood-2017-06-789842
M3 - Article
C2 - 29255068
AN - SCOPUS:85047733115
SN - 0006-4971
VL - 131
SP - 1012
EP - 1021
JO - Blood
JF - Blood
IS - 9
ER -