Differential cerebral hemometabolic responses to blood transfusions in adults and children with sickle cell anemia

Abstract

Background: Blood transfusions are administered to children and adults with sickle cell anemia (SCA) for secondary stroke prevention, or as treatment for recurrent pain crises or acute anemia, but transfusion effects on cerebral hemodynamics and metabolism are not well-characterized. Purpose: To compare blood transfusion-induced changes in hemometabolic parameters, including oxygen extraction fraction (OEF) and cerebral blood flow (CBF), within and between adults and children with SCA. Study Type: Prospective, longitudinal study. Subjects: Adults with SCA (n = 16) receiving simple (n = 7) or exchange (n = 9) transfusions and children with SCA (n = 11) receiving exchange transfusions were scanned once when hematocrit was near nadir and again within 7 days of transfusion. Adult controls without SCA or sickle trait (n = 7) were scanned twice on separate days. Field Strength/Sequence: 3.0T T 1 -weighted, T 2 -weighted, and T 2 -relaxation-under-spin-tagging (TRUST) imaging, and phase contrast angiography. Assessment: Global OEF was computed as the relative difference between venous oxygenation (from TRUST) and arterial oxygenation (from pulse oximetry). Global CBF was computed as total blood flow to the brain normalized by intracranial tissue volume. Statistical Tests: Hemometabolic variables were compared using two-sided Wilcoxon signed-rank tests; associations were analyzed using two-sided Spearman's correlation testing. Results: In adults with SCA, posttransfusion OEF = 0.38 ± 0.05 was lower (P = 0.001) than pretransfusion OEF = 0.45 ± 0.09. A change in OEF was correlated with increases in hematocrit (P = 0.02; rho = -0.62) and with pretransfusion hematocrit (P = 0.02; rho = 0.65). OEF changes after transfusion were greater (P = 0.002) in adults receiving simple versus exchange transfusions. Posttransfusion CBF = 77.7 ± 26.4 ml/100g/min was not different (P = 0.27) from pretransfusion CBF = 82.3 ± 30.2 ml/100g/min. In children with SCA, both posttransfusion OEF = 0.28 ± 0.04 and CBF = 76.4 ± 26.4 were lower than pretransfusion OEF = 0.36 ± 0.06 (P = 0.004) and CBF = 96.4 ± 16.5 (P = 0.004). Data Conclusion: Cerebral OEF reduces following transfusions in adults and children with SCA. CBF reduces following transfusions more often in children compared to adults, indicating that vascular reserve capacity may remain near exhaustion posttransfusion in many adults. Level of Evidence: 2 Technical Efficacy: Stage 5

Haploidentical bone marrow transplantation improves cerebral hemodynamics in adults with sickle cell disease

“…This is in contrast to FLT3-ITD-mutated AML in which there is a wide range of FLT3-ITD allelic ratios that represent the relative role of the FLT3-ITD mutation in driving disease phenotype. 3 These findings are contrary to a previous report that found that higher mutant NPM1 VAF was associated with worse survival. 4 The differences in these two studies could be attributed to several…”

“…These hemodynamic profiles have been associated with prior stroke and clinical impairment. 2 As a proof of principle that BMT improves cerebral hemodynamics via a decline or normalization in CBF and OEF, (Supporting Information Figure 1A) as is seen after blood transfusion with increased hematocrit (Hct), 3,4 For OEF quantification, T2 values from TRUST-MRI were converted to venous oxygen saturation (Yv) using previously characterized calibration curves. 2 Yv and arterial oxygenation saturation (Ya) were used to calculate OEF as the fractional difference of blood oxygenation in the arteries and veins, OEF = (Ya − Yv)/Ya.…”

“…2 Several studies have shown that higher FLT3-ITD allelic ratio is correlated with worse survival. 3 One single-center retrospective study suggested that higher variant allelic frequency (VAF) of mutant NPM1 was associated with worse overall survival (OS) and event-free survival (EFS) in newly diagnosed AML, particularly in patients with a DNMT3A mutation or who underwent hematopoietic stem cell transplantation (HSCT) in first remission. 4 In light of these data, we sought to determine the impact of mutant NPM1 VAF on outcomes in patients with newly diagnosed AML treated at our institution with idarubicin and cytarabine (IA)-based regimens.…”

Quantification of whole‐brain oxygenation extraction fraction and cerebral metabolic rate of oxygen consumption in adults with sickle cell anemia using individual T2‐based oxygenation calibrations

“…Previously, sickle blood was assumed to have blood T 2 calibration similar to normal blood . Using an existing T 2 calibration developed from normal blood, elevated OEF values were reported for the SCA volunteers, both with blood transfusion and without blood transfusion; however, another study measured T 2 values of sickle blood samples, showing about a 20% shorter T 2 value of sickle blood than the T 2 value of normal blood at the same Hct and Y. Based on these in vitro data, they developed a group‐based T 2 calibration specifically for sickle blood and observed reduced OEF and CMRO 2 of SCA patients …”

“…The discordant findings of OEF among SCA patients from the few MRI studies is perplexing. One possibility explaining the discrepancy could be the heterogeneity of sickled blood composition among different SCA participants.…”