Red cell distribution width (RDW) is a measure of the range of variation in erythrocyte volumes in terms of a coefficient of variation (CV) in percent. RDW can be reported statistically as a coefficient of variation (CV) and/or standard deviation (SD).
• RDW-CV, which represents the coefficient of variation in percent with respect to MCV, is expressed by the formula:
RDW = SD(MCV)/MCV × 100.
• RDW-SD, which reports in femtoliters the true value of the standard deviation obtained from the distribution of erythrocyte volumes measured at the height of 20% on the curve itself (Fig. 1).

Fig1. Graph representing the distribution of the erythrocyte population with RDW-CV and RDW-SD. (Copyright EDISES 2021. Reproduced with permission)
The reference range is between 12% and 15% (RDW-CV) and between 40 fl and 55 fL (RDW-SD), with variations depending on age and status (e.g., pregnancy). In evaluating this index, two factors that influence the variation of erythrocyte volumes within physiological ranges should be considered:
• Variability of production by the bone marrow, which is kept within narrow limits and controlled at the site by eliminating, through the medullary reticuloendothelial system, cells that cannot be released into circulation.
• The progressive aging of the circulating erythrocyte population is accompanied by a reduction in cell volume due to dehydration. Young red blood cells, since the reticulocyte state, are significantly more voluminous than red blood cells that have reached the end of their useful life, and, passing from one extreme to the other, a progressive and regular reduction in volume is observed. In many conditions of anemia, often high values of RDW are observed, so this index is used in association with MCV for a first differentiation among anemias that present similar characteristics; the most typical case is the differential diagnosis between two common microcytic anemias, the iron deficiency anemia and the β-thalassemic trait anemia, in which, besides a common reduced MCV, a high RDW value is more indicative of the first condition than the second one. Also, macrocytic anemia due to the deficiency of folate and vitamin B12 is characterized by an increase in RDW and an elevated MCV. However, it must be kept in mind that this is an index with relatively modest specificity and that, therefore, more specific tests must be associated with it. In recent years, interest in RDW has increased because an association between RDW and cardiovascular disease has been described. Specifically, increased levels of RDW are a predictor of adverse out comes in patients with cardiovascular diseases. Additionally, high RDW values have been described in several clinical conditions, including thromboembolic diseases, various cancers, diabetes, pulmonary diseases, kidney diseases, liver diseases, and other chronic disorders. The pathophysiological mechanisms underlying the RDW increase in these clinical conditions are not entirely understood, but erythrocyte eriptosis or apoptosis have been hypothesized. Eryptosis is a suicidal mechanism of the cell triggered by the entry of calcium ions, oxidative stress, alterations in the regulation of cytokines, and other mechanisms that occur in many chronic inflammatory diseases (e.g., heart and kidney failure), metabolic dis eases (e.g., diabetes), and others such as neoplasms.