Identifying Erythrocyte Injury in Toxicology Studies

The hematological impacts of a drug can affect erythropoiesis at the level of the bone marrow, or decrease the life span of the RBC (red blood cell). The most common and recognizable clinical manifestation of either type of drug-induced erythropoietic injury is a decrease in RBC mass, or what is clinically referred to as an anemia. A decrease in RBC production can generally be separated from increased destruction (hemolysis) by evaluation of the hemogram for evidence of regeneration. In most healthy mammalian species, hemolysis will result in a regenerative response characterized by an increase in circulating reticulocytes. Hemorrhage as an alternative cause of a regenerative anemia can generally be excluded by careful clinical evaluation of the animal. Subsequently, the investigation of a drug-induced regenerative anemia should involve a very thorough evaluation of RBC morphology for evidence of immune-mediated destruction, RBC oxidative injury, and fragmentation that can help to identify the underlying pathological mechanism(s) involved.