How do you evaluate for anemia?

Evaluation of Anemia: A Systematic Approach

Begin with a complete blood count (CBC) with indices and peripheral blood smear review, then use both morphologic (MCV-based) and kinetic (reticulocyte index) approaches to systematically identify the underlying cause. 1

Initial Laboratory Assessment

Order a CBC with indices as the foundation of your evaluation to determine if other cytopenias are present alongside the anemia. 1 The hemoglobin level is preferred over hematocrit because it has better reproducibility across laboratories and is not affected by sample storage time or patient variables like serum glucose. 1, 2

A peripheral blood smear review is critical to confirm RBC size, shape, and color, which provides essential diagnostic clues. 1 Abnormalities in two or more cell lines (white cells, hemoglobin, platelets) warrant hematology consultation as this suggests bone marrow dysfunction. 1

Morphologic Classification by MCV

Use the mean corpuscular volume to categorize the anemia into three types: 1

Microcytic Anemia (MCV < 80 fL)

• Most commonly iron deficiency; other causes include thalassemia, anemia of chronic disease, and sideroblastic anemia 1
• Order iron studies: serum iron, total iron-binding capacity (TIBC), transferrin saturation, and ferritin 1
• Absolute iron deficiency is defined as transferrin saturation <15% and ferritin <30 ng/mL 1

Normocytic Anemia (MCV 80-100 fL)

• May indicate hemorrhage, hemolysis, bone marrow failure, anemia of chronic inflammation, or renal insufficiency 1
• The reticulocyte count is the key follow-up test to distinguish between these causes 1

Macrocytic Anemia (MCV > 100 fL)

• Most commonly megaloblastic from vitamin B12 or folate deficiency due to insufficient uptake or inadequate absorption 1
• Non-megaloblastic causes include alcoholism, myelodysplastic syndromes, and drugs like hydroxyurea or diphenytoin 1

Kinetic Classification by Reticulocyte Index

Calculate the reticulocyte index (RI), which corrects the reticulocyte count for the degree of anemia to assess bone marrow production capacity. 1 Normal RI ranges from 1.0 to 2.0. 1

Low Reticulocyte Index (RI < 1.0)

• Indicates decreased RBC production 1
• Suggests iron deficiency, vitamin B12/folate deficiency, aplastic anemia, or bone marrow dysfunction from cancer or myelosuppressive therapy 1
• The most common reason for inadequate reticulocyte response in iron-replete patients is insufficient erythropoietin production or inflammation 1

High Reticulocyte Index (RI > 2.0)

• Indicates normal or increased RBC production 1
• Suggests ongoing blood loss or hemolysis as the cause of anemia 1
• Warrants evaluation for bleeding sources or hemolytic process 3, 4

Essential History and Physical Examination Elements

Document specific details including: 1

• Duration and time to onset of symptoms (syncope, exercise dyspnea, headache, vertigo, chest pain, fatigue disrupting daily activities, abnormal menstruation) 1
• Comorbidities and family history of hematologic disorders 1
• Exposure to drugs (antineoplastics, chemotherapy) and radiation 1
• Physical findings suggesting underlying causes: jaundice (hemolysis), splenic enlargement (hemolysis/hematologic malignancy), neurologic symptoms (B12 deficiency), blood in stool (GI bleeding), petechiae (thrombocytopenia), heart murmur (endocarditis), and pallor 1

Iron Status Assessment

Evaluate iron status using serum ferritin, transferrin saturation, and mean corpuscular volume. 1, 2 Transferrin saturation may be more reliable than ferritin in inflammatory states because ferritin acts as an acute-phase reactant and can be falsely elevated. 1, 2

In patients with iron deficiency who lack obvious blood loss sources (menstruation, known GI bleeding), carefully assess for occult gastrointestinal bleeding. 1, 2

Common Pitfalls to Avoid

• Do not rely solely on ferritin in inflammatory conditions as it can be falsely elevated; consider measuring C-reactive protein to assess inflammation's contribution 1, 2
• Do not assume anemia in CKD patients is solely from erythropoietin deficiency—they may have multiple contributing causes unrelated to kidney disease 1, 2
• Do not overlook that anemia of CKD is typically normochromic and normocytic, making it indistinguishable from anemia of other chronic conditions without proper evaluation 1
• In cancer patients, evaluate when hemoglobin falls to ≤11 g/dL or decreases by ≥2 g/dL from baseline, as multiple causes may coexist 1