Microcytic anemia: low MCV

Patients with a low MCV are likely to have iron deficiency anemia, although thalassemia and anemia of chronic disease are part of the differential.1 When the MCV is low, the serum ferritin level can help to distinguish between anemias. A serum ferritin level <20 µg/L is diagnostic of iron deficiency anemia. Patients whose serum ferritin is >20 µg/L should have their serum transferrin receptor level measured to aid in selecting further determinations.11,12 A low serum transferrin receptor level occurs in acute inflammation, protein deficiency and losses, and anemia of chronic disease. Patients with iron deficiency anemia have increased serum transferrin receptor levels.

Figure 2. Microcytic, hypochromic RBCs in a patient with iron deficiency anemiaThe RBC distribution width (RDW) has low specificity as an independent index, but it is useful in conjunction with the MCV when considering the etiology of microcytic anemia.2,7,8 The RDW is essentially the coefficient of variation in the measured RBC population.1 A normal RDW (<15%) indicates a homogeneous RBC population. A low RDW would indicate a more homogeneous or clonal RBC population, while an elevated RDW implies a heterogeneous RBC population. For example, iron deficiency anemia presents with a low MCV due to production of microcytic RBCs (Figure 2). However, the RDW is often increased owing to the wide coefficient of variation in RBC size.4,13 Note that an increased RDW is observed in iron deficiency anemia patients after treatment with iron therapy as newer RBCs are released from the bone marrow. Conversely, a patient with a low MCV that does not respond to iron therapy by production of increased RBCs of normal size would not exhibit an increased RDW. Thus, the value of this index lies in the post-treatment evaluation of anemias. A normal RDW may also be observed in mixed anemias, such as in patients with both iron deficiency (low MCV) and folate deficiency (high MCV).

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Iron: a crucial marker

Although serum iron can be measured directly, such measurements have limited usefulness as an independent marker. This is because inflammation and diurnal variation contribute to unstable iron levels. Nevertheless, in the evaluation of microcytic anemias, a decreased serum iron is an important indicator of depleted total iron stores as would be seen in iron deficiency anemia.7

Serum ferritin, a storage protein, is a sensitive marker of iron storage.1 As iron stores are depleted, the ferritin level also decreases.7 Ferritin is considered a nonspecific marker as well because it is also an acute phase reactant that may be increased in inflammatory processes.6,7

The serum transferrin receptor level indicates the amount of iron functionally available in the tissue iron stores.11,12 Unlike serum ferritin, the serum transferrin receptor level remains in the normal range during inflammatory processes, making it a more specific iron marker in patients with anemia.11

Free erythrocyte protoporphyrin is a heme precursor and an indirect reflection of iron in the heme molecule.1 Concentrations become elevated when serum iron levels are insufficient for RBC production, as occurs in iron deficiency anemia.7 Elevation may also be noted when there is interference in heme production, as happens in lead poisoning.1,6

Normocytic anemia: normal MCV

In the presence of a normal MCV, the most likely diagnoses are anemia of chronic disease, hemorrhage, renal disease, liver disease, endocrine dysfunction, and hypoplastic marrow.1 It is important to note that anemia of chronic disease may also present as a microcytic anemia (low MCV) depending on the duration of the primary illness. Similarly, early iron deficiency anemia may initially present as normocytic anemia.

For patients exhibiting a normal MCV, the next step in evaluation would be to assess the CBC findings for polychromasia or other abnormal morphology. Polychromasia dictates the need for a reticulocyte count. An elevated reticulocyte count is a sign of increased erythropoiesis1 and should lead to suspicions of hemolytic anemias.14

Since the early stages of both microcytic anemias and macrocytic anemias can present with a normal MCV, serum transferrin receptor, serum ferritin or serum B12, and folate levels should be employed when history and physical examination correlate with those etiologies.11,12