Proposed mechanism of neocytolysis. As the apparent concentration of EPO decreases, the permeability of the splenic endothelial cells (EC) increase (1) possibly secondary to an increase in macrophage-derived vascular endothelial growth factor (VEGF). ECs are stimulated to produce inflammatory cytokines along with VEGF (2) which cause upregulation of adhesion molecules on neocyte (NC) outer membranes and expression of phosphatidylserine (3). Macrophage processes interact with the neocytes and initiate eryptosis (4). Alternatively, erythroid progenitors (EP) in the bone marrow exposed to inflammatory conditions increase mitochondrial mass (5) which subsequently increases ROS production (6) and phosphatidylserine expression.