Diagnosing and Classifying Anemia in Adult Primary Care

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Anemia in adults is defined as hemoglobin less than 13 g/dL in males and 12 g/dL in females.6 The hemoglobin is part of the complete blood cell report, which also includes the white blood cell count (WBC), red blood cell count (RBC), hematocrit, platelet count, and indices.

When investigating the underlying cause of anemia, the most useful parts of the CBC are the hemoglobin and the mean corpuscular volume (MCV; see Table 2).6,10 The MCV is the average volume of red cells in a specimen. This parameter is used to classify the anemia as microcytic (MCV < 80 fL), normocytic (MCV 80-100 fL), or macrocytic (MCV > 100 fL), which helps to narrow the differential diagnosis and guide any further testing (see Figure).5,6,10

Normal Ranges for Laboratory Tests Used to Diagnose and Classify Anemia image

It is important to note that the normal ranges of the CBC parameters differ based on race, with persons of African ancestry having lower normal hemoglobin levels than persons of Caucasian ancestry.10 In addition, laboratories may have slightly different normal values for the CBC based on the equipment they utilize. Therefore, providers must follow their laboratory’s parameters, as well as adjust for the patient’s gender, age, and ethnicity.10

Microcytic Anemia

Iron deficiency

In microcytic anemia, the RBCs are smaller than average (MCV < 80 fL), as well as hypochromic due to lack of hemoglobin.9 Iron deficiency is the most common cause of microcytic anemia worldwide.11,12 Therefore, when a patient has microcytic anemia, a serum ferritin needs to be ordered. Further testing of total iron-binding capacity (TIBC), transferrin saturation, serum iron, and serum receptor levels may be helpful if the ferritin level is between 46-99 ng/mL and anemia due to iron deficiency is not confirmed (see Table 2).12

In iron deficiency anemia, serum ferritin and serum iron levels are low due to lack of iron, but serum TIBC is high.6 The elevated TIBC reflects increased synthesis of transferrin by the liver as it attempts to compensate for the patient’s low serum iron level.9 Since iron levels are controlled by absorption rather than excretion, iron is essentially only depleted from the body through blood loss.12 Therefore, an adult patient who is iron deficient has lost more iron through blood loss than was replaced through nutritional intake and gastrointestinal absorption. In children, increased growth-related iron requirements combined with poor nutritional intake of iron-rich foods is an additional mechanism for iron deficiency.11

Iron deficiency in all men and nonmenstruating women should always be worked up for possible blood loss due to abnormal (eg, gastrointestinal) bleeding or nonphysiologic (eg, poor dietary intake of iron) causes.11,12 Additional clinical findings associated with chronic iron deficiency include glossitis, angular stomatitis, and koilonych­ias (spoon-shaped nails).12

If the nutritional problem is corrected or the source of bleeding is controlled, treatment with oral or intravenous iron supplements should result in improved serum hemoglobin and reticulocyte counts.13 In the primary care setting, ferrous sulfate 325 mg, which provides 65 mg of elemental iron per tablet, orally three times daily is recommended for adults.13 This gives the patient the recommended dose of approximately 200 mg of elemental iron. Repeat hemoglobin and iron studies should be conducted again in three to six months.12,13

If the patient’s iron deficiency anemia does not improve after oral iron therapy, there may be a source of blood loss the provider missed or a problem with malabsorption of iron, which can be seen in those who have undergone gastric bypass surgery or who have inflammatory bowel disease.13 Such patients should be referred to a specialist, such as a gastroenterologist, for further evaluation.


Microcytic anemia with normal or elevated serum iron and normal-to-increased serum ferritin can be seen in patients with a type of thalassemia (see Figure).2 Thalassemias are inherited blood disorders that reduce hemoglobin production, leading to microcytosis; they are more common in those of Mediterranean, African, and Southeast Asian descent.2 Red cells in patients with a form of thalassemia are usually very small (microcytic) and have normal or elevated red cell distribution width (RDW).10

Classification of Anemia image

Moderate and severe forms of thalassemia can cause anemia. However, thalassemia syndromes that can cause severe (transfusion-dependent) anemia are usually diagnosed in childhood.9 Patients with one of the minor forms of thalassemia typically need minimal to no treatment.5 A patient with significant anemia suspicious for thalassemia should undergo hemoglobin electrophoresis testing to confirm the diagnosis and to determine the type of thalassemia.2 Typically, hemoglobin electrophoresis is normal in α thalassemia and is abnormal in ß thalassemia, as well as other forms of thalassemia. Referral to a hematologist for interpretation of these results and for further evaluation is appropriate.10

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