From the Guidelines
A comprehensive anemia workup should include a complete blood count (CBC) with differential, peripheral blood smear, reticulocyte count, iron studies (serum iron, total iron binding capacity, ferritin), vitamin B12 and folate levels, as these tests provide essential information for distinguishing between different types of anemia and guiding treatment decisions 1.
Initial Evaluation
The initial evaluation of anemia should involve a morphologic approach, characterizing the anemia based on the mean corpuscular volume (MCV) reported in the CBC test, which can be microcytic, normocytic, or macrocytic 1.
- Microcytic anemia is most commonly caused by iron deficiency, but can also be due to thalassemia, anemia of chronic disease, or sideroblastic anemia.
- Normocytic anemia may be caused by hemorrhage, hemolysis, bone marrow failure, anemia of chronic inflammation, or renal insufficiency, and the key follow-up test is the reticulocyte count.
- Macrocytic anemia is often megaloblastic, indicating vitamin B12 or folate deficiency, but can also be non-megaloblastic due to other causes such as alcoholism or certain drugs.
Kinetic Approach
The kinetic approach focuses on the underlying mechanism of anemia, distinguishing among production, destruction, and loss of red blood cells (RBCs) 1.
- The reticulocyte count corrected against the degree of anemia, or reticulocyte index (RI), is a crucial measurement for assessing RBC production capacity by the bone marrow.
- A low RI indicates decreased RBC production, suggesting iron deficiency, vitamin B12/folate deficiency, aplastic anemia, or bone marrow dysfunction.
- A high RI indicates normal or increased RBC production, suggesting blood loss or hemolysis in patients with anemia.
Additional Tests
Additional tests should be guided by the results of the initial evaluation and may include:
- Iron studies to assess for absolute iron deficiency, characterized by low transferrin saturation and ferritin levels 1.
- Vitamin B12 and folate levels to diagnose megaloblastic anemia.
- Stool guaiac and endoscopy findings to investigate hemorrhage.
- Coombs test, disseminated intravascular coagulation panel, low haptoglobin levels, and elevated indirect bilirubin to diagnose hemolysis.
- Glomerular filtration rate and erythropoietin level to assess kidney function.
- Personal and family history to suspect inherited anemia.
- Bone marrow biopsy to diagnose sideroblastic anemia or other bone marrow disorders.
Systematic Approach
A systematic approach to anemia workup, incorporating both morphologic and kinetic evaluations, as well as additional targeted tests based on initial findings, allows for accurate diagnosis and appropriate treatment of the underlying cause of anemia, ultimately improving patient outcomes in terms of morbidity, mortality, and quality of life 1.
From the Research
Anemia Workup Labs
- A complete blood count (CBC) is the initial step in the laboratory evaluation of anemia 2, 3, 4
- Reticulocyte count is a useful screen for hemolysis or blood loss and can help categorize the anemia as microcytic, macrocytic, or normocytic 2, 3, 4
- Examination of the peripheral smear can confirm the diagnosis and provide clues to the cause of anemia 2, 4
- Iron panel, including ferritin, iron levels, total iron-binding capacity, and transferrin saturation, can help diagnose iron deficiency anemia 2, 3, 4
- Reticulocyte hemoglobin content (CHr) is a useful marker for diagnosing iron deficiency and iron deficiency anemia, and monitoring iron therapy 5, 6
- Other tests, such as vitamin B12, folate, lactate dehydrogenase, haptoglobin, and bilirubin levels, may be ordered to investigate specific causes of anemia 3, 4
Diagnostic Approach
- The diagnosis of anemia is still complicated, and most tests have drawbacks 5
- A thorough history and physical examination, along with a CBC, are essential in the initial evaluation of anemia 3
- Supplemental tests, such as a peripheral blood smear and reticulocyte count, can help classify the anemia and guide further testing 2, 3, 4
- Molecular testing is increasingly being used to aid in the diagnostic process 4