TLR4 and sickle cell disease: For instance, sickle cell disease is a chronic inflammatory condition with hemolysis, vaso-occlusion, and ischemia-reperfusion due to the heme-induced MD-2/TLR4 activation leading to the production of pro-inflammatory mediators and a persistent activation of leukocytes, platelets, and endothelial cells (63, 110, 111, 138).