While patients occasionally present to a primary-care provider with signs and symptoms of anemia, the diagnosis is usually made from screening a complete blood count (CBC) in patients who are asymptomatic.1 In either case, the next step is to develop an appropriate treatment plan by identifying the cause of the anemia. This can be accomplished most efficiently by categorizing the anemia’s morphology.2 Casanova et al were able to eliminate the need for exhaustive workups by developing a clinical prediction rule for their obstetric patients based solely on CBC results and serum ferritin levels.3 This approach may offer a cost-effective, time-efficient, and readily employable method for evaluating the majority of anemia cases in the primary-care settings.4,5

RBC indices and morphology

Anemia can be classified by morphology based on (1) the size of the RBCs, (2) the amount of hemoglobin contained within the RBCs, and (3) the pathologic process causing the anemia.1,5,6 Laboratory evaluation of the anemic patient begins with consideration of hemoglobin concentrations and hematocrit, while RBC morphology and indices are frequently overlooked. In clinical practice, however, these parameters can be used to guide further testing and establish a diagnosis in anemic patients.5

Beginning the evaluation

Once the clinician has the CBC results, the first index to consider is the mean corpuscular volume (MCV). From this information alone, you will be able to categorize the anemia as microcytic (MCV <75 fL), normocytic (MCV within normal range of 75-100 fL), or macrocytic (MCV >100 fL).


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Figure 1. Blood smear from a patient with spherocytosis showing small RBCs with no central pallorThe MCV is an easily employable guide to the selection of additional tests. In one study, surveyed physicians regarded MCV as the single most useful RBC index in the evaluation of anemia.2 Respondents reported a low use of other RBC indices, including the RBC count itself, mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) data. Despite this finding, the MCHC is a useful index. An elevated MCHC can be a sign of spherocytosis (Figure 1), which may be associated with immune-mediated hemolytic anemia or may be an inherited defect of the erythrocyte cell membrane. Conversely, a low MCHC is often observed in iron deficiency anemia.1

A reticulocyte count can also be telling. It measures circulating immature erythrocytes.7 Any elevation suggests release of immature RBCs into the circulation and is considered an indicator of effective erythropoiesis.6,8 Conversely, a low reticulocyte count reflects insufficient bone marrow release of RBCs. The normal range of reticulocytes is 0.5%-1.5% of RBC populations.1,9 Iron deficiency anemia usually presents with a decreased reticulocyte count, indicating inadequate RBC production.1,6,10