Mean Corpuscular Volume (MCV)

Measurement of the MCV uses the effect of the average RBC size on the Hct. If the average RBC size is increased, the same number of RBCs will have a slightly larger cell mass and thus a slightly increased Hct reading; the opposite happens if the average RBC size is smaller than normal. The MCV is calculated by dividing the Hct value by the RBC count.

There is some disagreement in the literature on MCV reference ranges. Older sources and Coulter Company printed values are approximately :80-94 femtoliters (fL) for men and 81-99 fL for women. More recent reports are in substantial agreement on 80-100 fL for both sexes. Heavy smoking may increase the MCV as much as 3 fL.

Conditions that increase the MCV are listed in Table 2-1. In my experience, the most common cause of macrocytosis is alcoholism with or without cirrhosis. The major causes for folic acid deficiency are dietary deficiency or malabsorption; for vitamin B12 deficiency, pernicious anemia; and for substantial degrees of reticulocytosis, acute bleeding or hemolytic anemia. Occasionally there are mixed disorders; for example, some patients with alcoholism, malignancy, myxedema, and drug-induced macrocytosis have folic acid deficiency, and some patients with sideroblastic or sideroachrestic anemia have pyridoxine deficiency.

Some causes of increased mean corpuscular volume (macrocytosis)

Table 2-1 Some causes of increased mean corpuscular volume (macrocytosis)

It must be emphasized that a substantial number of patients with any disorder associated with macrocytosis will not display an elevated MCV when first seen by a physician. For example, 10%-20% of patients with megaloblastic anemia (folate or B12 deficiency) have normal range MCV (Table 2-1).

Conditions that decrease MCV are listed in Table 2-2; the most frequent (in the U.S. population) is chronic iron deficiency. The incidence of decreased MCV in chronic iron deficiency ranges from 27%-76% (averaging about 65%), depending considerably on the degree of deficiency. Thalassemia minor (alpha or beta) comprises about 15% of patients with microcytosis but may be less frequent in some populations. The anemia associated with various chronic diseases (uremia, rheumatoid-collagen diseases, severe chronic infection, etc.) is usually normocytic; but according to the literature, it can be microcytic in about 15% of patients (range, 0%-36%). In my experience, incidence has been 7% (100 patients). Differential diagnosis of these conditions is discussed in the section on chronic iron deficiency.

Some causes of decreased mean corpuscular volume (microcytosis)

Table 2-2 Some causes of decreased mean corpuscular volume (microcytosis)

Some reports in the literature indicate discrepancies when MCV data from microhematocrits are compared with results from automated cell counters such as the Coulter Counter. For example, one report noted that more than 30% of specimens in which the MCV fell below the lower reference range limit of 80 fL by Coulter Counter measurement were still within reference range when microhematocrits were used for the calculation. Another investigator found that macrocytes were reported on peripheral blood smear in only 65% of patients with elevated MCV by Coulter Counter measurement. These studies suggest that MCV values obtained using an automated cell counter are more sensitive to abnormality than other common hematologic parameters. On the other hand, in approximately 10%-20% of patients with an elevated MCV there was no adequate explanation for the abnormality (these patients usually had relatively small elevations, but small elevations do not imply nonsignificance). Also, a patient may have macrocytes in the peripheral blood smear with a normal MCV, since the MCV represents only the average RBC size.

Mean Corpuscular Hemoglobin (MCH)

The mean corpuscular hemoglobin (MCH) is based on estimates of the quantity (weight) of Hb in the average RBC. Calculation is done by dividing the blood Hb level by the RBC count. Reference values are 27-31 pg by manual methods and 26-34 pg by Coulter Counter.

The MCH is influenced by the size of the RBC; a large RBC with normal Hb content will contain a greater weight of Hb than a smaller cell with a normal hemoglobin content. The MCH also depends on the amount of Hb in relation to the size of the cell; a hypochromic cell has a smaller weight of Hb than a normochromic cell of equal size. In general, the MCH level is increased in macrocytosis and decreased in microcytosis and in hypochromia, but there is some variation because of the interplay between the two factors of cell size and concentration of Hb.

Recent articles have pointed out that MCH values from automated counting instruments closely parallel MCV, significantly more so than by calculation from manual measurements. Therefore, MCH levels from automated cell counters are said to add little if any useful information to that available from the MCV.

Mean Corpuscular Hemoglobin Concentration (MCHC)

The MCH concentration (MCHC) estimates the average concentration of Hb in the average RBC. The MCHC depends on the relationship of the amount of Hb to the volume of the RBC. Thus, the MCHC does not depend on cell size alone; a macrocyte with a normal amount of Hb has a normal MCHC. The MCHC is calculated by dividing the Hb value by the Hct value. Reference values are 32%-36% (320-360 g/L) (manual methods) or 31%% (Coulter Counter). Conditions that affect the MCHC are listed in Table 2-3.

Some conditions that affect the mean corpuscular hemoglobin concentration (MCHC)

Table 2-3 Some conditions that affect the mean corpuscular hemoglobin concentration (MCHC)*

Red Blood Cell Distribution Width (RDW)

Some of the newer electronic cell counting machines are able to sort out RBCs of different sizes and group them according to size (size histogram) as well as calculate the MCV. Normally, most RBCs are approximately equal in size, so that only one gaussian-type histogram peak is generated. Disease may change the size of some RBCs; for example, by fragmentation of RBCs (eg., in hemolysis) or by a gradual process of size change in newly produced RBCs (e.g., in folic acid or iron deficiency). In most cases the abnormal cell population coexists with normal (or at least, less affected) RBCs. The difference in size between the abnormal and less abnormal RBCs produces either more than one histogram peak or a broadening of the normal peak. The cell counting machines can calculate an index of the RBC size differences (anisocytosis) using data from the histogram and the MCV, called the RBC distribution width (RDW). Although the degree of abnormality determines whether or not the index value exceeds index population reference range, in general the RDW is elevated in factor deficiency (iron, folate, or B12), RBC fragmentation, and homozygous hemoglobinopathies (Hb SS, CC, and H) and is normal in thalassemia minor, anemia of chronic disease, and heterozygous trait combinations of abnormal hemoglobins with normal Hb A. The RDW index is never decreased. The RDW (like the MCV) is sometimes abnormal before anemia appears and may be abnormal even before the MCV. Different automated cell counters differ in the way they measure cell size and compute the index, and there may be differences in sensitivity of the index between instruments of different manufacturers and even between different instrument models of the same manufacturer (providing one source of confusion when data are evaluated in the literature and in patient reports). This means that each laboratory should obtain its own RDW reference range and also establish cutoff points for various diseases, which may be very difficult to do since some of the diseases are not common in every part of the country. Also, reports differ in percentage of patients with different diseases who have abnormal RDW (e.g., reports of elevated RDW in untreated pernicious anemia range from 69%-100%). Differentiation between various disorders affecting RBC using MCV and RDW are outlined in Table 2-4 (the diseases listed in each category do not include all patients with that disease).

Red blood cell distribution width and mean cell volume

Table 2-4 Red blood cell distribution width and mean cell volume


As an index of RBC hemoglobin, the MCHC was often more reliable than the MCV when manual counting methods were used, because manual RBC counts are relatively inaccurate. Since this is not a problem with automated cell counters, MCHC is not frequently helpful except to raise the question of spherocytosis if the MCHC is elevated. Increase in MCHC is usually limited to relatively severe RBC abnormalities. Elevated MCHC may be a clue to a false increase in MCV and decrease in Hct value due to cold agglutinins or to a false increase in Hb level due to hyperlipemia. However, different counting instruments react differently to cold agglutinins.
The MCV, MCH, and MCHC are affected only by average cell measurements either of size or of quantity of Hb. This is especially noticeable in the indices dependent on average RBC size (MCV and, to some extent, MCHC). There may be considerable variation in size between individual RBCs (anisocytosis), but average measurement indices do not reflect this, since they take into account only the average size.
Although careful examination of a well-made peripheral blood smear yields a considerable amount of the same information as RBC indices, abnormality may be indicated by one and not by the other, so that the two techniques are complementary.
Reference values for Hb, Hct, and indices for infants and children differ from adult values (see Table 37-1). There is some discrepancy in the literature regarding pediatric reference range values, more so than for adult reference ranges. Some of the reasons may be a more limited number of patients and the discrepancy between data derived from manual methods and data derived from automated cell counters.
It usually is not necessary to repeat RBC indices for screening or diagnostic purposes after one set of values has been obtained.