Erythrocyte glutamine depletion in sickle cell disease and its association with pulmonary hypertension. (A) Erythrocyte glutamine levels in healthy volunteers were similar to SCD patients without pulmonary hypertension (No PH, n = 23). However, glutamine levels were significantly decreased in SCD patients with a tricuspid regurgitant jet velocity (TRV) of at least 2.5 m/s on Doppler echocardiography (PH, n = 17) compared with SCD patients without PH (P < .001) and (B) erythrocyte glutamine levels inversely correlated with TRV on Doppler echocardiography (r = -0.51, P < .0001). (C) A significant reduction in the erythrocyte glutamine:glutamate ratio is identified in SCD compared with controls, with the lowest ratios identified in patients with PH. (D) The glutamine:glutamate ratio inversely correlated with TRV on Doppler echocardiography (r = −0.62, P < .001, Figure 2D), implicating glutamine bioavailability as a novel factor in the pathophysiology of PH.