AMPK underlies the detrimental role of CD73-mediated adenosine signaling in erythrocytes in SCD patients. Plasma adenosine levels were correlated to (A) plasma hemoglobin and (B) bilirubin. Plasma CD73 activity was correlated to plasma (C) hemoglobin and (D) bilirubin. (E-H) Changes in erythrocyte-phosphorylated AMPK level, 2,3-BPG mutase activity, 2,3-BPG concentrations and percentage of sickled cells in erythrocytes isolated from SCD patients after incubation under hypoxic conditions in the absence or presence of Bay Compound (ADORA2B agonist), AICAR (AMPK agonist), Bay Compound + Compound C (AMPK antagonist), Compound C, respectively. *P < .05 vs normoxic condition; **P < .05 vs untreated samples under hypoxic condition; #P < .05 versus Bay Compound–treated samples under hypoxic condition. ##P < .05 vs untreated samples under hypoxic condition.