Anemia is a frequently encountered problem in the
critically ill patient. The inability to compensate for
anemia includes several mechanisms, collectively referred to as
anemia of
inflammation: reduced production of
erythropoietin, impaired bone marrow response to
erythropoietin, reduced
iron availability, and increased red blood cell (RBC) clearance. This review focuses on mechanisms of RBC clearance during
inflammation. We state that
phosphatidylserine (PS) expression in
inflammation is mainly enhanced due to an increase in
ceramide, caused by an increase in
sphingomyelinase activity due to either
platelet activating factor,
tumor necrosis factor-α, or direct production by bacteria. Phagocytosis of RBCs during
inflammation is mediated via RBC
membrane protein band 3. Reduced deformability of RBCs seems an important feature in
inflammation, also mediated by band 3 as well as by
nitric oxide,
reactive oxygen species, and
sialic acid residues. Also, adherence of RBCs to the endothelium is increased during
inflammation, most likely due to increased expression of endothelial adhesion molecules as well as PS on the RBC membrane, in combination with decreased capillary blood flow. Thereby, clearance of RBCs during
inflammation shows similarities to clearance of senescent RBCs, but also has distinct entities, including increased adhesion to the endothelium.