What is the appropriate workup for severe anemia (low red blood cell count)?

From the Guidelines

A severe anemia workup should begin with a complete blood count (CBC) with differential, peripheral blood smear, reticulocyte count, and iron studies (ferritin, iron, TIBC, transferrin saturation) as the initial step in evaluating the underlying cause of anemia, as recommended by the most recent and highest quality study 1.

Initial Evaluation

The initial evaluation of severe anemia should include:

• Complete blood count (CBC) with differential to determine the mean corpuscular volume (MCV) and classify the anemia as microcytic, normocytic, or macrocytic
• Peripheral blood smear to evaluate the morphology of red blood cells
• Reticulocyte count to assess the bone marrow's response to anemia
• Iron studies, including ferritin, iron, TIBC, and transferrin saturation, to evaluate for iron deficiency

Additional Testing

Additional testing should be guided by the results of the initial evaluation and may include:

• Vitamin B12 and folate levels to evaluate for deficiencies
• Hemolysis markers, such as LDH, haptoglobin, and bilirubin, to evaluate for hemolytic anemia
• Renal function tests to evaluate for kidney disease
• Inflammatory markers, such as CRP and ESR, to evaluate for chronic inflammation
• Coombs test and hemoglobin electrophoresis for suspected hemolytic anemia

Treatment

Treatment of severe anemia depends on the underlying cause, but may include:

• Iron supplementation (ferrous sulfate 325mg three times daily) for iron deficiency
• Vitamin B12 injections (1000mcg IM daily for one week, then weekly for one month, then monthly) for B12 deficiency
• Folate supplementation (1mg daily) for folate deficiency
• Blood transfusion for severe anemia (hemoglobin <7 g/dL) with hemodynamic instability

Bone Marrow Evaluation

Bone marrow aspiration and biopsy may be necessary if myelodysplastic syndrome or other bone marrow disorders are suspected, as recommended by 1.

The workup is comprehensive because anemia can result from decreased production (nutritional deficiencies, bone marrow disorders), increased destruction (hemolysis), or blood loss, and identifying the specific mechanism is crucial for effective treatment, as noted in 1.

From the Research

Severe Anemia Workup

• The workup for severe anemia typically involves a thorough history and physical examination, as well as laboratory tests such as a complete blood cell count (CBC) 2.
• The CBC can provide important clues to the classification and cause of anemia, including the mean corpuscular volume (MCV) 2.
• Supplemental tests may include a peripheral blood smear, reticulocyte count, iron panel, and levels of vitamin B12, folate, lactate dehydrogenase, haptoglobin, and bilirubin 2.
• Reticulocyte hemoglobin content (CHr) is a useful marker for diagnosing iron deficiency and iron deficiency anemia, and can be used to monitor response to iron therapy 3, 4.
• CHr has a moderate sensitivity and specificity for diagnosing iron deficiency, and is less affected by inflammation than other biomarkers such as serum iron, transferrin saturation, and ferritin 3.

Laboratory Evaluation

• A complete blood cell count (CBC) is essential in the evaluation of anemia, and can provide information on the severity of the anemia and the presence of other abnormalities such as leukocytosis or thrombocytosis 2, 5.
• The reticulocyte count can help distinguish between acute and chronic anemia, and can provide information on the bone marrow's response to anemia 2, 4.
• Iron studies, including serum iron, transferrin saturation, and ferritin, can help diagnose iron deficiency anemia, but may be affected by inflammation and other conditions 3, 2.

Diagnosis and Treatment

• The diagnosis of anemia can be classified into different types, including microcytic, normocytic, and macrocytic anemia, based on the MCV 2, 5.
• Treatment of anemia depends on the underlying cause, and may include iron supplementation, vitamin B12 or folate supplementation, and blood transfusions 2, 5, 6.
• In patients with severe anemia, a restrictive transfusion strategy (i.e. transfusing for hemoglobin < 6-8 g/dL) may be associated with better outcomes than a more liberal transfusion strategy 6.