Anemia of the Critically Ill Patient: Pathophysiology, Lessons from Animal Models

Abstract

Critically ill patients have a high prevalence of anemia. Some of them are already anemic at intensive care unit (ICU) admission, because of surgery, trauma, or their medical history; and around 80 % of them are anemic at ICU discharge. The mechanisms underlying this anemia are multiple and often entangled. Two main mechanisms are involved: inflammation and blood losses. Inflammation is a major contributor to this anemia, with similarities with “anemia of inflammation” or “anemia of chronic disease,” by impairing bone marrow erythropoiesis, repressing erythropoietin synthesis, and decreasing red blood cell life span. Blood losses are important during ICU hospitalization, due to invasive procedures (drainage, catheterizations, dialysis), occult bleedings (gastrointestinal), and repeated blood samplings. These blood losses are directly responsible for hemoglobin loss but also for iron losses. The resulting iron deficiency slows erythropoiesis and contributes to worsen the anemia. Interestingly, inflammation interacts with iron metabolism too. Indeed, proinflammatory cytokines (notably IL-6) induce hepcidin synthesis, the master regulator of iron metabolism, which prevents the release of iron from store cells (macrophages and duodenal cells). The resulting hypoferremia due to the repressed iron mobilization from stores is called “functional iron deficiency.” Different animal models have been used to explore all these mechanisms. These models involve mainly rodents (mice and rats) and helped to better describe the link between inflammation and erythropoiesis, and the interaction between inflammation, iron deficiency, and iron metabolism. However, new animal or human studies are needed to improve our knowledge on the pathophysiology of this anemia and to evaluate therapeutic targets such as hepcidin modifications or iron treatment.