RT Journal
A1 Ballas SK
T1 NEurocognitive complications of sickle cell anemia in adults
JF JAMA
JO JAMA
YR 2010
FD May 12
VO 303
IS 18
SP 1862
OP 1863
DO 10.1001/jama.2010.610
UL http://dx.doi.org/10.1001/jama.2010.610
AB 
Recent studies suggest that the pathogenesis of the complications of SCD involves 2 distinct pathways: vaso-occlusion and hemolysis.4 The primary process that leads to vaso-occlusion is the polymerization of hemoglobin (Hb) S on deoxygenation. This results in cellular dehydration and distortion of the shape and decreased deformability and stickiness of red blood cells that promotes their adhesion to vascular endothelium.5- 6 The vaso-occlusive pathway is associated with painful crises, acute chest syndrome, and avascular necrosis. The hemolytic pathway begins with intravascular destruction of red blood cells and the release of free hemoglobin and arginase into the plasma.4 Free hemoglobin binds and inactivates nitric oxide and, concomitantly, free arginase converts L-arginine, a nitric oxide substrate, into ornithinine, thus reducing the production of nitric oxide.4 Reduced levels of nitric oxide cause vasoconstriction. Dysregulation of nitric oxide homeostasis secondary to hemolysis seems to be associated with pulmonary hypertension, priapism, and leg ulcers.4