Red cell indices in classification and treatment of anemias: from M. M. Wintrobes's original 1934 classification to the third millennium

Purpose of review Measurements of red cell volume, hemoglobin (Hb) concentration and Hb content continue to play a crucial role in the differential diagnosis of anemias 80 years after the publication of Wintrobe's seminal work. Modern hematology analyzers provide additional data on the heterogeneity of these parameters (distribution width) and quantify similar parameters of reticulocytes as well. Red cell and reticulocyte cellular indices are widely used in the diagnosis and monitoring of hematological diseases. Recent findings Quantification of hypochromic cells is valuable in the differential diagnosis of thalassemia trait and iron deficiency, and in monitoring therapeutic response to erythropoietic stimulating agents, while hyperchromic cells are an essential diagnostic component for hereditary spherocytosis and may correlate with hemolytic parameters in sickle cell disease. Values for these parameters however depend on the technology used. Red cell clearance is associated with a reduction in both Hb content and cell volume: normal cells are likely to be removed by the time they reach a volume of 72 fl. Reticulocyte parameters such as Hb content (CHr or ret-He) or maturity index (RMI) have shown value in a variety of hematological conditions. New findings from genetic association studies have identified several potential novel genes affecting red cell indices, which are not mediated by changes in iron availability. Summary Red cell indices continue to provide an essential support to the diagnosis and monitoring of hematological diseases.