The release of intravascular haemoglobin mobs up nitric acid which has a vasodilatation effect. This aggravates the already deficient tissue perfusion. A vicious circle is formed that eventually leads to tissue hypoxia, sequestration of blood in organs with sinuses (spleen, liver, lungs and the penis). There is also a chronic haemolytic anaemia with insufficient increase in the production of erythropoietin due to the fact that the beta S globin chain has a lower affinity for oxygen and therefore releases oxygen easily to the tissue. To further reduce erythropoiesis is the increase of inflammatory cytokines that inhibit haemopoiesis i.e interleukin 1 and tumor necrotic factor. On the other hand an increase in the red cell mass tends to increase vascular occlusion and ischemic crises. The ideal stable haematocrit for sickle cell disease is therefore between 24% and 28%. At this range of haematocrit, tissue hypoxia is minimized and painful crises are easier to control.